In this study an effort has been made to use plant polyphenol oxidases; potato (Solanum tuberosum) and brinjal (Solanum melongena), for the treatment of various important dyes used in textile and other industries....In this study an effort has been made to use plant polyphenol oxidases; potato (Solanum tuberosum) and brinjal (Solanum melongena), for the treatment of various important dyes used in textile and other industries. The ammonium sulphate fractionated enzyme preparations were used to treat a number of dyes under various experimental conditions. Majority of the treated dyes were maximally decolorized at pH 3.0. Some of the dyes were quickly decolorized whereas others were marginally decolorized. The initial first hour was sufficient for the maximum decolorization of dyes. The rate of decolorization was quite slow on long treatment of dyes. Enhancement in the dye decolorization was noticed on increasing the concentration of enzymes. The complex mixtures of dyes were treated with both preparations of polyphenol oxidases in the buffers of varying pH values. Potato polyphenol oxidase was significantly more effective in decolorizing the dyes to higher extent as compared to the enzyme obtained from brinjal polyphenol oxidase. Decolorization of dyes and their mixtures, followed by the formation of an insoluble precipitate, which could be easily removed simply by centrifugation.展开更多
Background: Glucose oxidase(GOD), an aerobic dehydrogenase, has been used as an antibiotic substitute in feed.A study was conducted to evaluate the differential effects of 2 different GODs fermented by Aspergillus nig...Background: Glucose oxidase(GOD), an aerobic dehydrogenase, has been used as an antibiotic substitute in feed.A study was conducted to evaluate the differential effects of 2 different GODs fermented by Aspergillus niger or Penicillium amagasakiense on caecal microbiota and to further illuminate the potential roles of changes in the gut microbiota in regulating the growth performance and meat quality of broiler chickens.Results: A total of 420 one-day-old healthy Arbor Acres broilers were randomly assigned to 4 treatments: the control group,the antibiotic growth promoter(AGP) supplementation group, and the GOD-A and GOD-P(GODs produced by A. niger and P. amagasakiense, respectively) groups. As a result, supplementation with GOD produced by P. amagasakiense could significantly improve the average daily weight gain and average daily feed intake of broilers before 21 days of age by significantly increasing the enzymatic activities of jejunal amylase and those of ileal amylase, chymotrypsin, and lipase in21-day-old broilers and could increase the enzymatic activities of duodenal amylase, jejunal amylase and lipase, and ileal chymotrypsin and lipase in 42-day-old broilers. Meanwhile, compared with AGP treatment, supplementation with GOD produced by P. amagasakiense significantly decreased the L value of 21-day-old broilers and the Δp H and L* value of 42-day-old broilers, while supplementation with GOD produced by A. niger significantly increased the p H24 hvalue of 21-day-old and 42-day-old broilers by reducing plasma malondialdehyde content. By using 16 S r RNA sequencing, we found that the beneficial bacteria and microbiota in broilers were not disturbed but were improved by GOD supplementation compared with ADP treatment, including the genera Eubacterium and Christensenel a and the species uncultured_Eubacterium_sp,Clostridium_asparagiforme, and uncultured_Christensenel a_sp, which were positively related to the improved intestinal digestive enzymatic activities, growth performance, and meat quality of broilers.Conclusion: The altered gut microbiota induced by supplementation with glucose oxidase produced by P. amagasakiense mediate better regulatory effects on the meat quality and growth performance of broilers than that induced by supplementation with glucose oxidase produced by A. niger.展开更多
Aims: We focused on DNA methylation of the promoter regions of the Monoamine Oxidase (MAO) A and B genes from postmortem brains of subjects with schizophrenia. Methods: We determined levels of DNA methylation using ge...Aims: We focused on DNA methylation of the promoter regions of the Monoamine Oxidase (MAO) A and B genes from postmortem brains of subjects with schizophrenia. Methods: We determined levels of DNA methylation using genomic DNA samples purified from four brain areas: prefrontal cortex (PFC), hippocampus, occipital cortex and nucleus accumbens (NAc), by a bisulfite sequencing method from seven normal subjects and six subjects with schizophrenia. Results: Although very few methylated CpGs of the MAOA and MAOB genes were detected in male samples, various DNA methylation patterns were present in female samples, and some differences were found in such patterns between normal subjects and subjects with schizophrenia. In the PFC, the average level of methylation of both genes was significantly higher in subjects with schizophrenia than in normal subjects. The content of highly methylated alleles of the MAOA gene in the NAc was significantly associated with schizophrenia, with similar results obtained for the MAOB gene in both the NAc and PFC. Some CpG sites showed higher levels of methylation in schizophrenia than in normal subjects. Conclusions: Levels of methylation were quite high in NAc and PFC in female subjects with schizophrenia compared with those in female normal subjects.展开更多
Age-related Ecto-Nicotinamide Adenine Dinucleotide Oxidase Disulfide Thiol Exchangers 3 (ENOX3) or age-related NADH oxidases (arNOX) are expressed at the cell surface as five members of the TM-9 superfamily, initially...Age-related Ecto-Nicotinamide Adenine Dinucleotide Oxidase Disulfide Thiol Exchangers 3 (ENOX3) or age-related NADH oxidases (arNOX) are expressed at the cell surface as five members of the TM-9 superfamily, initially membrane anchored, all functionally similar, with the N-termini exposed at the cell’s exterior. ECTO-NOXes are cell surface proteins with both time-keeping CoQH2 [NAD(P)H] oxidase and protein disulfidethiol interchange activities. They are designated as ECTO-NOX proteins because of their localization on the outer surface of the plasma membrane and to distinguish them from the phox-NOXes of host defense. A ca. 30 kDa N-terminal fragment is cleaved and accumulates in body fluids (serum, saliva, urine, perspiration). arNOXes appear around age 30 and increase steadily thereafter. Reduced quinones, i.e., reduced coenzyme Q, of the plasma membrane are natural substrates. NAD(P)H is oxidized as an artificial substrate. In one phase of the arNOX cycle electrons are transferred to oxygen to generate superoxide. Substrates for the shed forms of arNOX appear to be proteins of body fluids. Circulating lipoproteins and skin matrix proteins emerge as potentially important health-related targets. Through oxidation of collagen, elastin and other proteins of the skin matrix, arNOXes are major contributors to skin aging through tyrosine and thiol oxidation and subsequent cross linking. The main destructive action of arNOX, however, may be to directly oxidize circulating lipoproteins. arNOX in the blood is structured as an integral component of the LDL particle through site-specific binding. As such, arNOXes are implicated as major risk factors for cardiovascular disease due to specific oxidation of LDLs. The superoxide produced and its conversion to hydrogen peroxide would be one part of the potentially destructive properties by contribution to lipid oxidation. Inhibition of arNOX proteins provides a rational basis for anti-aging interventions and their elimination as a major risk factor of atherogenesis.展开更多
Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NAD...Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.展开更多
Benthodytes occidentpalauta sp.nov.was collected from the Kyushu-Palau Ridge at a depth of 5481 m in 2021.This new species is characterized by a gelatinous body wall,violet skin,six pairs of dorsal papillae,and a roug...Benthodytes occidentpalauta sp.nov.was collected from the Kyushu-Palau Ridge at a depth of 5481 m in 2021.This new species is characterized by a gelatinous body wall,violet skin,six pairs of dorsal papillae,and a rough mid-ventral surface without tube feet.The dorsal deposits are rod-shaped and tripartite.Two types of papillae deposits as crosses with four arms with central bipartite apophyses.Ventral deposits are rods.Tentacle ossicles are rod-shaped with end protrusions.Gonad deposits are rodshaped,tripartite,and cross-shaped.The phylogenetic analyses based on cytochrome oxidase subunit 1(COI)and 16S individually and a concatenated dataset of COI and 16S genes of this species support that B.occidentpalauta sp.nov.belongs to Benthodytes.展开更多
Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced ...Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.展开更多
BACKGROUND Metabolic reprogramming plays a key role in cancer progression and clinical outcomes;however,the patterns and primary regulators of metabolic reprogramming in colorectal cancer(CRC)are not well understood.A...BACKGROUND Metabolic reprogramming plays a key role in cancer progression and clinical outcomes;however,the patterns and primary regulators of metabolic reprogramming in colorectal cancer(CRC)are not well understood.AIM To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)in promoting progression of CRC.METHODS We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.Consensus clustering was used to cluster CRC based on dysregulated metabolic genes.A prediction model was constructed based on survival-related metabolic genes.Sphere formation,migration,invasion,proliferation,apoptosis and clone formation was used to evaluate the biological function of NOX4 in CRC.mRNA sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor cells.In vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor growth.RESULTS We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic genes.Among these genes,NOX4 was highly expressed in tumor tissues and correlated with worse survival.In vitro,NOX4 overexpression induced clone formation,migration,invasion,and stemness in CRC cells.Furthermore,RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling pathway.Trametinib,a MEK1/2 inhibitor,abolished the NOX4-mediated tumor progression.In vivo,NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis,whereas trametinib treatment can reversed the metastasis.CONCLUSION Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis,suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4.展开更多
Objective: To analyze the possible mechanism of Pueraria isoflavones inhibiting XOD and GLUT9 to reduce uric acid production and promote uric acid excretion. Methods: August 2021-April 2022, a total of forty SPF male ...Objective: To analyze the possible mechanism of Pueraria isoflavones inhibiting XOD and GLUT9 to reduce uric acid production and promote uric acid excretion. Methods: August 2021-April 2022, a total of forty SPF male Kunming mice were divided into the healthy group (carboxymethylcellulose sodium at a dose of 250 mg/kg), the model group (HUA mice were given carboxymethylcellulose sodium at a dose of 250 mg/kg), the low group (HUA mice were given pueraria isoflavone at a dose of 125 mg/kg), HUA mice were given pueraria isoflavones at a dose of 250 mg/kg once d frequency)and the high group (HUA mice were given pueraria isoflavones at a dose of 500 mg/kg once d frequency) dosage groups, with 8 mice in each group. The contents of uric acid (SUA), urea nitrogen (BUN) and creatinine (SCr) in serum and urine of each group were compared before and after intervention (30 d). Statistical differences of xanthine oxidase (XOD) and human glucose transporter 9(GLUT9), cy- clooxygenase- 2(COX-2), tumor necrosis factor (TNF-α) and interleukin-1 (IL-1β) contents in renal tissues of each group after intervention (30 d) were compared. Results: After intervention, kidney inflammatory factors (COX-2, TNF-α and IL-1β) in the model group were compared. Blood and urine indexes (SUA, BUN, SCr);The contents of XOD and GLUT9 were higher than those of healthy group(P<0.05). Renal inflammatory cytokines (COX-2, TNF-α and IL-1β) in low, medium and high dose groups;Blood and urine indexes (SUA, BUN, SCr);The contents of XOD and GLUT9 were lower than those of model group, and there were low > medium > high dose groups, the comparison between the two groups had statistical significance(P< 0.05). After intervention, the contents of 3 indicators in blood or urine(COX-2, TNF-α and IL-1β) all decreased compared with before intervention, and the differences in intra-group comparison were statistically significant (P<0.05). Conclusion: Pueraria isoflavones can treat HUA mice by inhibiting the expression of XOD and GLUT9, and then play a role in reducing uric acid pro- duction and promoting uric acid excretion, as well as alleviating the degree of disease inflammation.展开更多
Copper-radical oxidases(CROs)catalyze the two-electron oxidation of a large number of primary alcohols includ-ing carbohydrates,polyols and benzylic alcohols as well as aldehydes and𝛼-hydroxy-carbonyl compound...Copper-radical oxidases(CROs)catalyze the two-electron oxidation of a large number of primary alcohols includ-ing carbohydrates,polyols and benzylic alcohols as well as aldehydes and𝛼-hydroxy-carbonyl compounds while reducing molecular oxygen to hydrogen peroxide.Initially,CROs like galactose oxidase and glyoxal oxidase were identified only in fungal secretomes.Since the last decade,their representatives have also been identified in some bacteria.CROs are grouped in the AA5 family of“auxiliary activities”in the database of Carbohydrate-Active enzymes.Despite low overall sequence similarity and different substrate specificities,sequence alignments and the solved crystal structures revealed a conserved architecture of the active sites in all CROs,with a mononuclear copper ion coordinated to an axial tyrosine,two histidines,and a cross-linked cysteine-tyrosyl radical cofactor.This unique post-translationally modified protein cofactor has attracted much attention in the past,which resulted in a large number of reports that shed light on key steps of the catalytic cycle and physico-chemical properties of CROs.Thanks to their broad substrate spectrum accompanied by the only need for molecular oxygen for catal-ysis,CROs since recently experience a renaissance and have been applied in various biocatalytic processes.This review provides an overview of the structural features,catalytic mechanism and substrates of CROs,presents an update on the engineering of these enzymes to improve their expression in recombinant hosts and to enhance their activity,and describes their potential fields of biotechnological application.展开更多
The synergistic effects of cellobiose dehydro-genase (CDH) and manganese-dependent peroxidases (MnP) on the degradation of kraft pulp cellulolytic enzyme lignin (CEL) were investigated. Addition of CDH significantly i...The synergistic effects of cellobiose dehydro-genase (CDH) and manganese-dependent peroxidases (MnP) on the degradation of kraft pulp cellulolytic enzyme lignin (CEL) were investigated. Addition of CDH significantly increased the amount of water-soluble products reduced from CEL by MnP. CDH facilitated the reduction of the contents of methoxyl, carboxyl, phenolic hydroxyl and total hydroxyl groups of CEL by MnP. 1H-NMR analysis showed that addition of CDH also decreased further the amount of protons of CEL degraded by MnP. The results proved for the first time that CDH could promote degradation of lignin by MnP and suggest that CDH could not only promote degradation of cellulose but also is an important part of the lignin biodeg-radation system.展开更多
Apoplastic ascorbate oxidases(AOs)play a critical role in reactive oxygen species(RoS)-mediated innate host immunity by regulating the apoplast redox state.To date,little is known about how apoplastic effectors of the...Apoplastic ascorbate oxidases(AOs)play a critical role in reactive oxygen species(RoS)-mediated innate host immunity by regulating the apoplast redox state.To date,little is known about how apoplastic effectors of the riceblast fungus Magnaportheoryzaemodulate the apoplast redox state of rice to subvert plant immunity.In this study,we demonstrated that M.oryzae MoAo1 is an Ao that plays a role in virulence by modulating the apoplast redox status of rice cells.We showed that MoAo1 inhibits the activity of rice OsAO3and OsAO4,which also regulate the apoplast redox status and plant immunity.In addition,we found that MoAo1,OsAO3,andOsAO4 allexhibit polymorphic variations whosevaried interactions orchestrate pathogen virulence and rice immunity.Taken together,our results reveal a critical role for extracellular redox enzymes during rice blast infection and shed light on the importance of the apoplast redox state anditsregulation inplant-pathogeninteractions.展开更多
Potato(Solanum tuberosum L.)is susceptible to enzymatic browning after fresh processing,resulting in color change and potential alteration in the nutritional quality.In this study,a popular potato cultivar,Feiwuruita,...Potato(Solanum tuberosum L.)is susceptible to enzymatic browning after fresh processing,resulting in color change and potential alteration in the nutritional quality.In this study,a popular potato cultivar,Feiwuruita,was used to profile the metabolites involved in color and nutritional quality changes in fresh shreds stored at 0 and 4 h at 25°C(designated CK and CK4H,respectively).The shreds turned brown within 4 h of storage.In all,723 metabolites consisting 12 classes of compounds were detected in the samples,largely lipids,phenolic acids,alkaloids,amino acids and derivatives,flavonoids,organic acids,nucleotides and derivatives.Of these,163 metabolites accumulated differentially between CK and CK4H shreds.Polyphenolic compounds(phenolic acids and flavonoids)mostly increased in the shreds after 4 h storage.Conversely,the short-term storage drastically reduced lipid compounds(25 LysoPC and 19 LysoPE),while essential alkaloids and terpenoid compounds that are beneficial to human health increased in accumulation.The findings present global metabolome and nutritional composition changes in short-term stored shreds of Feiwuruita.This study provides important foundation for future studies on browning prevention/reduction and for better utilization of Feiwuruita.展开更多
Litchi(Litchi chinensis Sonn.)is a type of commercially prevalent subtropical and tropical fruit.Since litchi has a highly heterozygous genetic background and a long reproductive cycle,conventional breeding methods(su...Litchi(Litchi chinensis Sonn.)is a type of commercially prevalent subtropical and tropical fruit.Since litchi has a highly heterozygous genetic background and a long reproductive cycle,conventional breeding methods(such as hybridization)have limited ability to nurture new litchi cultivars.Here,an efficient and stable Agrobacterium tumefaciens-mediated genetic transformation of embryogenic callus was established in‘Feizixiao’litchi.Transgenic materials were verified using polymerase chain reaction(PCR)analysis,β-glucuronidase(GUS)assay,and green fluorescent protein(GFP)assay.To implement the technology of the Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)/associated protein 9(CRISPR/Cas9)technology in‘Feizixiao’litchi and verify the validity of these transformation systems,the litchi polyphenol oxidase gene(LcPPO,JF926153)was knocked out.Various categories of mutations,covering base insertions,deletions,and substitutions,were found in transgenic materials via sequence analysis.The transformation system achieved high feasibility and efficiency,and the system of CRISPR/Cas9 was successfully employed to edit genes in‘Feizixiao’litchi.This work provides an essential foundation for investigating the functions of genes and accelerating litchi genetic improvement.展开更多
Water scarcity impairs maize growth and yield.Identification and deployment of superior droughttolerance alleles is desirable for the genetic improvement of stress tolerance in maize.Our previous study revealed that m...Water scarcity impairs maize growth and yield.Identification and deployment of superior droughttolerance alleles is desirable for the genetic improvement of stress tolerance in maize.Our previous study revealed that maize sulfite oxidase(SO) catalyzes the oxidation of sulfite to sulfate and may be involved in drought response.But it was unclear whether the natural variation in Zm SO is directly associated with the drought resistance of maize.In the present study,we showed that Zm SO was associated with drought tolerance in maize seedlings,using gene association analysis and a transgene approach.A 14-bp insertion variation,containing two ABA-responsive elements,in the promoter region of Zm SO conferred ABAinducible expression,leading to increased drought tolerance.Genetic selection of this favorable allele increased drought tolerance.This study has identified elite alleles associated with sulfur metabolism for improving maize drought resistance.展开更多
BACKGROUND Ferroptosis is involved in developing inflammatory diseases;yet,its role in acute hypertriglyceridemic pancreatitis(HTGP)remains unclear.AIM To explore whether ferroptosis is involved in the process of HTGP...BACKGROUND Ferroptosis is involved in developing inflammatory diseases;yet,its role in acute hypertriglyceridemic pancreatitis(HTGP)remains unclear.AIM To explore whether ferroptosis is involved in the process of HTGP and elucidate its potential mechanisms.METHODS An HTGP mouse model was induced using intraperitoneal injection of P-407 and caerulein(CAE).Then,pancreatic tissues from the model animals were subjected to proteome sequencing analysis.The pathological changes and scores of the pancreas,lung,and kidney were determined using hematoxylin-eosin staining.The levels of serum amylase(AMY),triglyceride,and total cholesterol were measured with an automatic blood cell analyzer.Additionally,the serum levels of tumor necrosis factor(TNF)-α,interleukin(IL)-6,and IL-1βwere determined by enzyme linked immunosorbent assay.Malonaldehyde(MDA),glutathione(GSH),and Fe^(2+)were detected in the pancreas.Finally,immunohistochemistry was performed to assess the expression of ferroptosis-related proteins.RESULTS Proteome sequencing revealed that ferroptosis was involved in the process of HTGP and that NADPH oxidase(NOX)2 may participate in ferroptosis regulation.Moreover,the levels of serum AMY,TNF-α,IL-6,and IL-1βwere significantly increased,MDA and Fe^(2+)were upregulated,GSH and ferroptosis-related proteins were reduced,and the injury of the pancreas,lung,and kidney were aggravated in the P407+CAE group compared to CAE and wild type groups(all P<0.05).Notably,the inhibition of ferroptosis and NOX2 attenuated the pathological damage and the release of TNF-α,IL-6,and IL-1βin the serum of the mice.CONCLUSION Ferroptosis was found to have an important role in HTGP and may be considered a potential target for clinical treatment.展开更多
Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious...Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious cycle leading to reactive oxygen species accumulation,resulting in progression of the pathological process.Therefore,breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage.Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4(NADPH oxidase 4,NOX4)led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage.The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress,mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage.We found that NOX4 knockdown by adeno-associated virus(AAV-NOX4)in rats enhanced neuronal tolerance to oxidative stress,enabling them to better resist the oxidative stress caused by intracerebral hemorrhage.Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria,relieved mitochondrial damage,prevented secondary reactive oxygen species accumulation,reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats.Finally,we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4.The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis,which is similar to the effect of AAV-NOX4.This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production,and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage.展开更多
Benthodytes tetrapapillata sp.nov.was collected from a seamount located on the Caroline Ridge at a depth of 2289 m,during the cruise of R/V Kexue in June 2019.We provided detailed descriptions of external and deposits...Benthodytes tetrapapillata sp.nov.was collected from a seamount located on the Caroline Ridge at a depth of 2289 m,during the cruise of R/V Kexue in June 2019.We provided detailed descriptions of external and deposits morphology.The phylogenetic analyses based on cytochrome c oxidase I(COI)and a concatenated dataset of 16S and COI genes showed that the new species belonged to Benthodytes that is not monophyletic.Both details of morphological comparisons and molecular analyses confirmed that Benthodytes tetrapapillata sp.nov.is a new psychropotid species.A state of main morphological characters in valid species of Benthodytes is also provided in this study.展开更多
Developing flexible bioelectronics is essential to the realization of artificial intelligence devices and biomedical applications, such as wearables, but their potential is limited by sustainable energy supply. An enz...Developing flexible bioelectronics is essential to the realization of artificial intelligence devices and biomedical applications, such as wearables, but their potential is limited by sustainable energy supply. An enzymatic biofuel cell(BFC) is promising for power supply, but its use is limited by the challenges of incorporating multiple enzymes and rigid platforms. This paper shows the first example of screen-printable nanocomposite inks engineered for a single-enzyme-based energy-harvesting device and a self-powered biosensor driven by glucose on bioanode and biocathode. The anode ink is modified with naphthoquinone and multiwalled carbon nanotubes(MWCNTs), whereas the cathode ink is modified with Prussian blue/MWCNT hybrid before immobilizing with glucose oxidase. The flexible bioanode and the biocathode consume glucose. This BFC yields an open circuit voltage of 0.45 V and a maximum power density of 266 μW cm-2. The wearable device coupled with a wireless portable system can convert chemical energy into electric energy and detect glucose in artificial sweat. The self-powered sensor can detect glucose concentrations up to 10 mM. Common interfering substances,including lactate, uric acid, ascorbic acid, and creatinine, have no effect on this self-powered biosensor. Additionally, the device can endure multiple mechanical deformations. New advances in ink development and flexible platforms enable a wide range of applications, including on-body electronics, self-sustainable applications, and smart fabrics.展开更多
Targeting key enzymes that generate oxalate precursors or substrates is an alternative strategy to eliminate primary hyperoxaluria type I(PH1),the most common and lifethreatening type of primary hyperoxaluria.The comp...Targeting key enzymes that generate oxalate precursors or substrates is an alternative strategy to eliminate primary hyperoxaluria type I(PH1),the most common and lifethreatening type of primary hyperoxaluria.The compact Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)from the Prevotella and Francisella 1(Cpf1)protein simplifies multiplex gene editing and allows for all-in-one adeno-associated virus(AAV)delivery.We hypothesized that the multiplex capabilities of the Cpf1system could help minimize oxalate formation in PH1 by simultaneously targeting the hepatic hydroxyacid oxidase 1(Hao1)and lactate dehydrogenase A(Ldha)genes.Study cohorts included treated PH1 rats(Agxt Q84X rats injected with AAV-AsCpf1 at 7 days of age),phosphate-buffered saline(PBS)-injected PH1 rats,untreated PH1 rats,and age-matched wild-type(WT)rats.The most efficient and specific CRISPR RNA(crRNA)pairs targeting the rat Hao1and Ldha genes were initially screened ex vivo.In vivo experiments demonstrated efficient genome editing of the Hao1 and Ldha genes,primarily resulting in small deletions.This resulted in decreased transcription and translational expression of Hao1 and Ldha.Treatment significantly reduced urine oxalate levels,reduced kidney damage,and alleviated nephrocalcinosis in rats with PH1.No liver toxicity,ex-liver genome editing,or obvious offtarget effects were detected.We demonstrated the AAVAsCpf1 system can target multiple genes and rescue the pathogenic phenotype in PH1,serving as a proof-ofconcept for the development of multiplex genome editingbased gene therapy.展开更多
文摘In this study an effort has been made to use plant polyphenol oxidases; potato (Solanum tuberosum) and brinjal (Solanum melongena), for the treatment of various important dyes used in textile and other industries. The ammonium sulphate fractionated enzyme preparations were used to treat a number of dyes under various experimental conditions. Majority of the treated dyes were maximally decolorized at pH 3.0. Some of the dyes were quickly decolorized whereas others were marginally decolorized. The initial first hour was sufficient for the maximum decolorization of dyes. The rate of decolorization was quite slow on long treatment of dyes. Enhancement in the dye decolorization was noticed on increasing the concentration of enzymes. The complex mixtures of dyes were treated with both preparations of polyphenol oxidases in the buffers of varying pH values. Potato polyphenol oxidase was significantly more effective in decolorizing the dyes to higher extent as compared to the enzyme obtained from brinjal polyphenol oxidase. Decolorization of dyes and their mixtures, followed by the formation of an insoluble precipitate, which could be easily removed simply by centrifugation.
基金supported by the National Natural Science Foundation of China (31972529, 31902184)the National Key Research and Development Projects (2017YFD0500500)the China Postdoctoral Science Foundation(2019M653774)。
文摘Background: Glucose oxidase(GOD), an aerobic dehydrogenase, has been used as an antibiotic substitute in feed.A study was conducted to evaluate the differential effects of 2 different GODs fermented by Aspergillus niger or Penicillium amagasakiense on caecal microbiota and to further illuminate the potential roles of changes in the gut microbiota in regulating the growth performance and meat quality of broiler chickens.Results: A total of 420 one-day-old healthy Arbor Acres broilers were randomly assigned to 4 treatments: the control group,the antibiotic growth promoter(AGP) supplementation group, and the GOD-A and GOD-P(GODs produced by A. niger and P. amagasakiense, respectively) groups. As a result, supplementation with GOD produced by P. amagasakiense could significantly improve the average daily weight gain and average daily feed intake of broilers before 21 days of age by significantly increasing the enzymatic activities of jejunal amylase and those of ileal amylase, chymotrypsin, and lipase in21-day-old broilers and could increase the enzymatic activities of duodenal amylase, jejunal amylase and lipase, and ileal chymotrypsin and lipase in 42-day-old broilers. Meanwhile, compared with AGP treatment, supplementation with GOD produced by P. amagasakiense significantly decreased the L value of 21-day-old broilers and the Δp H and L* value of 42-day-old broilers, while supplementation with GOD produced by A. niger significantly increased the p H24 hvalue of 21-day-old and 42-day-old broilers by reducing plasma malondialdehyde content. By using 16 S r RNA sequencing, we found that the beneficial bacteria and microbiota in broilers were not disturbed but were improved by GOD supplementation compared with ADP treatment, including the genera Eubacterium and Christensenel a and the species uncultured_Eubacterium_sp,Clostridium_asparagiforme, and uncultured_Christensenel a_sp, which were positively related to the improved intestinal digestive enzymatic activities, growth performance, and meat quality of broilers.Conclusion: The altered gut microbiota induced by supplementation with glucose oxidase produced by P. amagasakiense mediate better regulatory effects on the meat quality and growth performance of broilers than that induced by supplementation with glucose oxidase produced by A. niger.
文摘Aims: We focused on DNA methylation of the promoter regions of the Monoamine Oxidase (MAO) A and B genes from postmortem brains of subjects with schizophrenia. Methods: We determined levels of DNA methylation using genomic DNA samples purified from four brain areas: prefrontal cortex (PFC), hippocampus, occipital cortex and nucleus accumbens (NAc), by a bisulfite sequencing method from seven normal subjects and six subjects with schizophrenia. Results: Although very few methylated CpGs of the MAOA and MAOB genes were detected in male samples, various DNA methylation patterns were present in female samples, and some differences were found in such patterns between normal subjects and subjects with schizophrenia. In the PFC, the average level of methylation of both genes was significantly higher in subjects with schizophrenia than in normal subjects. The content of highly methylated alleles of the MAOA gene in the NAc was significantly associated with schizophrenia, with similar results obtained for the MAOB gene in both the NAc and PFC. Some CpG sites showed higher levels of methylation in schizophrenia than in normal subjects. Conclusions: Levels of methylation were quite high in NAc and PFC in female subjects with schizophrenia compared with those in female normal subjects.
文摘Age-related Ecto-Nicotinamide Adenine Dinucleotide Oxidase Disulfide Thiol Exchangers 3 (ENOX3) or age-related NADH oxidases (arNOX) are expressed at the cell surface as five members of the TM-9 superfamily, initially membrane anchored, all functionally similar, with the N-termini exposed at the cell’s exterior. ECTO-NOXes are cell surface proteins with both time-keeping CoQH2 [NAD(P)H] oxidase and protein disulfidethiol interchange activities. They are designated as ECTO-NOX proteins because of their localization on the outer surface of the plasma membrane and to distinguish them from the phox-NOXes of host defense. A ca. 30 kDa N-terminal fragment is cleaved and accumulates in body fluids (serum, saliva, urine, perspiration). arNOXes appear around age 30 and increase steadily thereafter. Reduced quinones, i.e., reduced coenzyme Q, of the plasma membrane are natural substrates. NAD(P)H is oxidized as an artificial substrate. In one phase of the arNOX cycle electrons are transferred to oxygen to generate superoxide. Substrates for the shed forms of arNOX appear to be proteins of body fluids. Circulating lipoproteins and skin matrix proteins emerge as potentially important health-related targets. Through oxidation of collagen, elastin and other proteins of the skin matrix, arNOXes are major contributors to skin aging through tyrosine and thiol oxidation and subsequent cross linking. The main destructive action of arNOX, however, may be to directly oxidize circulating lipoproteins. arNOX in the blood is structured as an integral component of the LDL particle through site-specific binding. As such, arNOXes are implicated as major risk factors for cardiovascular disease due to specific oxidation of LDLs. The superoxide produced and its conversion to hydrogen peroxide would be one part of the potentially destructive properties by contribution to lipid oxidation. Inhibition of arNOX proteins provides a rational basis for anti-aging interventions and their elimination as a major risk factor of atherogenesis.
基金supported by the National Research Foundation of the Republic of Korea 2018R1D1A3B07047960the Soonchunhyang University Research Fund(to SSY).
文摘Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.
基金the National Key R&D Program of China(No.2022YFC2803902)the Project of State Key Laboratory of Satellite Ocean Environment Dynamics,Second Institute of Oceanography,MNR(No.SOEDZZ2002)the Scientific Research Fund of the Second Institute of Oceanography,MNR(No.SZ2101)。
文摘Benthodytes occidentpalauta sp.nov.was collected from the Kyushu-Palau Ridge at a depth of 5481 m in 2021.This new species is characterized by a gelatinous body wall,violet skin,six pairs of dorsal papillae,and a rough mid-ventral surface without tube feet.The dorsal deposits are rod-shaped and tripartite.Two types of papillae deposits as crosses with four arms with central bipartite apophyses.Ventral deposits are rods.Tentacle ossicles are rod-shaped with end protrusions.Gonad deposits are rodshaped,tripartite,and cross-shaped.The phylogenetic analyses based on cytochrome oxidase subunit 1(COI)and 16S individually and a concatenated dataset of COI and 16S genes of this species support that B.occidentpalauta sp.nov.belongs to Benthodytes.
文摘Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.
基金Supported by Henan Province Medical Science and Technology Research Provincial and Ministry Co-constructed Projects,No.SBGJ202101010Major Public Welfare Projects in Henan Province,No.201300310400+1 种基金Joint Construction Project of Henan Medical Science and Technology Research Plan,No.LHGJ20220050Major Science and Technology Project of Henan Province,No.221100310100.
文摘BACKGROUND Metabolic reprogramming plays a key role in cancer progression and clinical outcomes;however,the patterns and primary regulators of metabolic reprogramming in colorectal cancer(CRC)are not well understood.AIM To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)in promoting progression of CRC.METHODS We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.Consensus clustering was used to cluster CRC based on dysregulated metabolic genes.A prediction model was constructed based on survival-related metabolic genes.Sphere formation,migration,invasion,proliferation,apoptosis and clone formation was used to evaluate the biological function of NOX4 in CRC.mRNA sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor cells.In vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor growth.RESULTS We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic genes.Among these genes,NOX4 was highly expressed in tumor tissues and correlated with worse survival.In vitro,NOX4 overexpression induced clone formation,migration,invasion,and stemness in CRC cells.Furthermore,RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling pathway.Trametinib,a MEK1/2 inhibitor,abolished the NOX4-mediated tumor progression.In vivo,NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis,whereas trametinib treatment can reversed the metastasis.CONCLUSION Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis,suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4.
基金National Innovation and Entrepreneurship Training Program for College Students(No.S202010823014)Hunan Provincial College Student Innovation Training Project,No.(2021)199(S202110823045)。
文摘Objective: To analyze the possible mechanism of Pueraria isoflavones inhibiting XOD and GLUT9 to reduce uric acid production and promote uric acid excretion. Methods: August 2021-April 2022, a total of forty SPF male Kunming mice were divided into the healthy group (carboxymethylcellulose sodium at a dose of 250 mg/kg), the model group (HUA mice were given carboxymethylcellulose sodium at a dose of 250 mg/kg), the low group (HUA mice were given pueraria isoflavone at a dose of 125 mg/kg), HUA mice were given pueraria isoflavones at a dose of 250 mg/kg once d frequency)and the high group (HUA mice were given pueraria isoflavones at a dose of 500 mg/kg once d frequency) dosage groups, with 8 mice in each group. The contents of uric acid (SUA), urea nitrogen (BUN) and creatinine (SCr) in serum and urine of each group were compared before and after intervention (30 d). Statistical differences of xanthine oxidase (XOD) and human glucose transporter 9(GLUT9), cy- clooxygenase- 2(COX-2), tumor necrosis factor (TNF-α) and interleukin-1 (IL-1β) contents in renal tissues of each group after intervention (30 d) were compared. Results: After intervention, kidney inflammatory factors (COX-2, TNF-α and IL-1β) in the model group were compared. Blood and urine indexes (SUA, BUN, SCr);The contents of XOD and GLUT9 were higher than those of healthy group(P<0.05). Renal inflammatory cytokines (COX-2, TNF-α and IL-1β) in low, medium and high dose groups;Blood and urine indexes (SUA, BUN, SCr);The contents of XOD and GLUT9 were lower than those of model group, and there were low > medium > high dose groups, the comparison between the two groups had statistical significance(P< 0.05). After intervention, the contents of 3 indicators in blood or urine(COX-2, TNF-α and IL-1β) all decreased compared with before intervention, and the differences in intra-group comparison were statistically significant (P<0.05). Conclusion: Pueraria isoflavones can treat HUA mice by inhibiting the expression of XOD and GLUT9, and then play a role in reducing uric acid pro- duction and promoting uric acid excretion, as well as alleviating the degree of disease inflammation.
基金This work was supported by the Ministry of Innovation,Science and Research the state of North Rhine-Westphalia,Germany within the framework of the NRW-Strategieprojekt BioSC(No.313/323-400-00213)together with the“European Regional Development Fund(EFRE)”,Project“Clus-ter Industrial Biotechnology(CLIB)Kompetenzzentrum Biotechnologie(CKB)”(34.EFRE-0300095/1703FI04)Financial support by the Scien-tific and Technological Research Council of Turkey(TUBITAK)2219-International Research Fellowship Programme for Saadet Alpdagtas is gratefully acknowledged.
文摘Copper-radical oxidases(CROs)catalyze the two-electron oxidation of a large number of primary alcohols includ-ing carbohydrates,polyols and benzylic alcohols as well as aldehydes and𝛼-hydroxy-carbonyl compounds while reducing molecular oxygen to hydrogen peroxide.Initially,CROs like galactose oxidase and glyoxal oxidase were identified only in fungal secretomes.Since the last decade,their representatives have also been identified in some bacteria.CROs are grouped in the AA5 family of“auxiliary activities”in the database of Carbohydrate-Active enzymes.Despite low overall sequence similarity and different substrate specificities,sequence alignments and the solved crystal structures revealed a conserved architecture of the active sites in all CROs,with a mononuclear copper ion coordinated to an axial tyrosine,two histidines,and a cross-linked cysteine-tyrosyl radical cofactor.This unique post-translationally modified protein cofactor has attracted much attention in the past,which resulted in a large number of reports that shed light on key steps of the catalytic cycle and physico-chemical properties of CROs.Thanks to their broad substrate spectrum accompanied by the only need for molecular oxygen for catal-ysis,CROs since recently experience a renaissance and have been applied in various biocatalytic processes.This review provides an overview of the structural features,catalytic mechanism and substrates of CROs,presents an update on the engineering of these enzymes to improve their expression in recombinant hosts and to enhance their activity,and describes their potential fields of biotechnological application.
基金This work was supported by the National Natural Science Foundation of China (Grant Nos. 20077015 and 29906005) by the Special Foundation of the Ministry of Education of China (Grant No. 200023).
文摘The synergistic effects of cellobiose dehydro-genase (CDH) and manganese-dependent peroxidases (MnP) on the degradation of kraft pulp cellulolytic enzyme lignin (CEL) were investigated. Addition of CDH significantly increased the amount of water-soluble products reduced from CEL by MnP. CDH facilitated the reduction of the contents of methoxyl, carboxyl, phenolic hydroxyl and total hydroxyl groups of CEL by MnP. 1H-NMR analysis showed that addition of CDH also decreased further the amount of protons of CEL degraded by MnP. The results proved for the first time that CDH could promote degradation of lignin by MnP and suggest that CDH could not only promote degradation of cellulose but also is an important part of the lignin biodeg-radation system.
基金This research was supported by the China National Funds for Innovative Research Groups(31721004)the key program of the Natural Science Foundation of China(NSFC)(32030091)+3 种基金the NSFC Youth Program(31901832)Youth Program for Natural Science Foundation of Jiangsu Province(BK2019054)the program of NSFC-DFG(31861133017)the NSFC program(32172377)。
文摘Apoplastic ascorbate oxidases(AOs)play a critical role in reactive oxygen species(RoS)-mediated innate host immunity by regulating the apoplast redox state.To date,little is known about how apoplastic effectors of the riceblast fungus Magnaportheoryzaemodulate the apoplast redox state of rice to subvert plant immunity.In this study,we demonstrated that M.oryzae MoAo1 is an Ao that plays a role in virulence by modulating the apoplast redox status of rice cells.We showed that MoAo1 inhibits the activity of rice OsAO3and OsAO4,which also regulate the apoplast redox status and plant immunity.In addition,we found that MoAo1,OsAO3,andOsAO4 allexhibit polymorphic variations whosevaried interactions orchestrate pathogen virulence and rice immunity.Taken together,our results reveal a critical role for extracellular redox enzymes during rice blast infection and shed light on the importance of the apoplast redox state anditsregulation inplant-pathogeninteractions.
基金research was funded by Major Science and Technology Project of Xiamen,China(3502Z20211004)Xiamen Science and Technology Assistance Project(3502Z20194509,3502Z20204504-2,3502Z20204501-3).
文摘Potato(Solanum tuberosum L.)is susceptible to enzymatic browning after fresh processing,resulting in color change and potential alteration in the nutritional quality.In this study,a popular potato cultivar,Feiwuruita,was used to profile the metabolites involved in color and nutritional quality changes in fresh shreds stored at 0 and 4 h at 25°C(designated CK and CK4H,respectively).The shreds turned brown within 4 h of storage.In all,723 metabolites consisting 12 classes of compounds were detected in the samples,largely lipids,phenolic acids,alkaloids,amino acids and derivatives,flavonoids,organic acids,nucleotides and derivatives.Of these,163 metabolites accumulated differentially between CK and CK4H shreds.Polyphenolic compounds(phenolic acids and flavonoids)mostly increased in the shreds after 4 h storage.Conversely,the short-term storage drastically reduced lipid compounds(25 LysoPC and 19 LysoPE),while essential alkaloids and terpenoid compounds that are beneficial to human health increased in accumulation.The findings present global metabolome and nutritional composition changes in short-term stored shreds of Feiwuruita.This study provides important foundation for future studies on browning prevention/reduction and for better utilization of Feiwuruita.
基金supported by grants from the National Key R&D Program of China(Grant No.2019YFD1000900)the Hainan Province Science and Technology Special Fund(Grant No.ZDYF2022XDNY253)the earmarked fund for CARS(Grant No.CARS-32-01)。
文摘Litchi(Litchi chinensis Sonn.)is a type of commercially prevalent subtropical and tropical fruit.Since litchi has a highly heterozygous genetic background and a long reproductive cycle,conventional breeding methods(such as hybridization)have limited ability to nurture new litchi cultivars.Here,an efficient and stable Agrobacterium tumefaciens-mediated genetic transformation of embryogenic callus was established in‘Feizixiao’litchi.Transgenic materials were verified using polymerase chain reaction(PCR)analysis,β-glucuronidase(GUS)assay,and green fluorescent protein(GFP)assay.To implement the technology of the Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)/associated protein 9(CRISPR/Cas9)technology in‘Feizixiao’litchi and verify the validity of these transformation systems,the litchi polyphenol oxidase gene(LcPPO,JF926153)was knocked out.Various categories of mutations,covering base insertions,deletions,and substitutions,were found in transgenic materials via sequence analysis.The transformation system achieved high feasibility and efficiency,and the system of CRISPR/Cas9 was successfully employed to edit genes in‘Feizixiao’litchi.This work provides an essential foundation for investigating the functions of genes and accelerating litchi genetic improvement.
基金financially supported by the National Natural Science Foundation of China (31971894)。
文摘Water scarcity impairs maize growth and yield.Identification and deployment of superior droughttolerance alleles is desirable for the genetic improvement of stress tolerance in maize.Our previous study revealed that maize sulfite oxidase(SO) catalyzes the oxidation of sulfite to sulfate and may be involved in drought response.But it was unclear whether the natural variation in Zm SO is directly associated with the drought resistance of maize.In the present study,we showed that Zm SO was associated with drought tolerance in maize seedlings,using gene association analysis and a transgene approach.A 14-bp insertion variation,containing two ABA-responsive elements,in the promoter region of Zm SO conferred ABAinducible expression,leading to increased drought tolerance.Genetic selection of this favorable allele increased drought tolerance.This study has identified elite alleles associated with sulfur metabolism for improving maize drought resistance.
基金Supported by the National Natural Science Foundation of Shandong Province,No.ZR2021MH032.
文摘BACKGROUND Ferroptosis is involved in developing inflammatory diseases;yet,its role in acute hypertriglyceridemic pancreatitis(HTGP)remains unclear.AIM To explore whether ferroptosis is involved in the process of HTGP and elucidate its potential mechanisms.METHODS An HTGP mouse model was induced using intraperitoneal injection of P-407 and caerulein(CAE).Then,pancreatic tissues from the model animals were subjected to proteome sequencing analysis.The pathological changes and scores of the pancreas,lung,and kidney were determined using hematoxylin-eosin staining.The levels of serum amylase(AMY),triglyceride,and total cholesterol were measured with an automatic blood cell analyzer.Additionally,the serum levels of tumor necrosis factor(TNF)-α,interleukin(IL)-6,and IL-1βwere determined by enzyme linked immunosorbent assay.Malonaldehyde(MDA),glutathione(GSH),and Fe^(2+)were detected in the pancreas.Finally,immunohistochemistry was performed to assess the expression of ferroptosis-related proteins.RESULTS Proteome sequencing revealed that ferroptosis was involved in the process of HTGP and that NADPH oxidase(NOX)2 may participate in ferroptosis regulation.Moreover,the levels of serum AMY,TNF-α,IL-6,and IL-1βwere significantly increased,MDA and Fe^(2+)were upregulated,GSH and ferroptosis-related proteins were reduced,and the injury of the pancreas,lung,and kidney were aggravated in the P407+CAE group compared to CAE and wild type groups(all P<0.05).Notably,the inhibition of ferroptosis and NOX2 attenuated the pathological damage and the release of TNF-α,IL-6,and IL-1βin the serum of the mice.CONCLUSION Ferroptosis was found to have an important role in HTGP and may be considered a potential target for clinical treatment.
基金supported by the National Natural Science Foundation of China,No.81671125the Natural Science Foundation of Guangdong Province,No.2021A1515011115Guangzhou Science and Technology Project,No.202102010346(all to YZC)。
文摘Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious cycle leading to reactive oxygen species accumulation,resulting in progression of the pathological process.Therefore,breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage.Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4(NADPH oxidase 4,NOX4)led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage.The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress,mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage.We found that NOX4 knockdown by adeno-associated virus(AAV-NOX4)in rats enhanced neuronal tolerance to oxidative stress,enabling them to better resist the oxidative stress caused by intracerebral hemorrhage.Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria,relieved mitochondrial damage,prevented secondary reactive oxygen species accumulation,reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats.Finally,we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4.The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis,which is similar to the effect of AAV-NOX4.This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production,and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage.
基金Supported by the National Key Research and Development Program of China (No.2021YFE0193700)the Strategic Priority Research Program of the Chinese Academy of Sciences (No.XDB42000000)+3 种基金the National Natural Science Foundation of China (No.41930533)the Biological Resources ProgramChinese Academy of Sciences (No.KFJ-BRP-017-38)the Major Scientific and Technological Projects of Hainan Province (No.ZDKJ2021036)。
文摘Benthodytes tetrapapillata sp.nov.was collected from a seamount located on the Caroline Ridge at a depth of 2289 m,during the cruise of R/V Kexue in June 2019.We provided detailed descriptions of external and deposits morphology.The phylogenetic analyses based on cytochrome c oxidase I(COI)and a concatenated dataset of 16S and COI genes showed that the new species belonged to Benthodytes that is not monophyletic.Both details of morphological comparisons and molecular analyses confirmed that Benthodytes tetrapapillata sp.nov.is a new psychropotid species.A state of main morphological characters in valid species of Benthodytes is also provided in this study.
基金supported by National Research Council of Thailand NRCT (grant number: N41A640129), Prince of Songkla University, Hat Yai, Thailandthe Talent Management Project of Prince of Songkla Universitythe Center of Excellence for Innovation in Chemistry (PERCH-CIC), Ministry of Higher Education, Science, Research, and Innovation (MHESI)。
文摘Developing flexible bioelectronics is essential to the realization of artificial intelligence devices and biomedical applications, such as wearables, but their potential is limited by sustainable energy supply. An enzymatic biofuel cell(BFC) is promising for power supply, but its use is limited by the challenges of incorporating multiple enzymes and rigid platforms. This paper shows the first example of screen-printable nanocomposite inks engineered for a single-enzyme-based energy-harvesting device and a self-powered biosensor driven by glucose on bioanode and biocathode. The anode ink is modified with naphthoquinone and multiwalled carbon nanotubes(MWCNTs), whereas the cathode ink is modified with Prussian blue/MWCNT hybrid before immobilizing with glucose oxidase. The flexible bioanode and the biocathode consume glucose. This BFC yields an open circuit voltage of 0.45 V and a maximum power density of 266 μW cm-2. The wearable device coupled with a wireless portable system can convert chemical energy into electric energy and detect glucose in artificial sweat. The self-powered sensor can detect glucose concentrations up to 10 mM. Common interfering substances,including lactate, uric acid, ascorbic acid, and creatinine, have no effect on this self-powered biosensor. Additionally, the device can endure multiple mechanical deformations. New advances in ink development and flexible platforms enable a wide range of applications, including on-body electronics, self-sustainable applications, and smart fabrics.
基金partially supported by the Science and Technology Commission of Shanghai Municipality (22YF1426900,20140900200)National Natural Science Foundation of China (32001057)。
文摘Targeting key enzymes that generate oxalate precursors or substrates is an alternative strategy to eliminate primary hyperoxaluria type I(PH1),the most common and lifethreatening type of primary hyperoxaluria.The compact Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)from the Prevotella and Francisella 1(Cpf1)protein simplifies multiplex gene editing and allows for all-in-one adeno-associated virus(AAV)delivery.We hypothesized that the multiplex capabilities of the Cpf1system could help minimize oxalate formation in PH1 by simultaneously targeting the hepatic hydroxyacid oxidase 1(Hao1)and lactate dehydrogenase A(Ldha)genes.Study cohorts included treated PH1 rats(Agxt Q84X rats injected with AAV-AsCpf1 at 7 days of age),phosphate-buffered saline(PBS)-injected PH1 rats,untreated PH1 rats,and age-matched wild-type(WT)rats.The most efficient and specific CRISPR RNA(crRNA)pairs targeting the rat Hao1and Ldha genes were initially screened ex vivo.In vivo experiments demonstrated efficient genome editing of the Hao1 and Ldha genes,primarily resulting in small deletions.This resulted in decreased transcription and translational expression of Hao1 and Ldha.Treatment significantly reduced urine oxalate levels,reduced kidney damage,and alleviated nephrocalcinosis in rats with PH1.No liver toxicity,ex-liver genome editing,or obvious offtarget effects were detected.We demonstrated the AAVAsCpf1 system can target multiple genes and rescue the pathogenic phenotype in PH1,serving as a proof-ofconcept for the development of multiplex genome editingbased gene therapy.