High Levels Of H2O2 Research Articles

Decreased Levels of Thioredoxin o1 Influences Stomatal Development and Aperture but Not Photosynthesis under Non-Stress and Saline Conditions.

Salinity has a negative impact on plant growth, with photosynthesis being downregulated partially due to osmotic effect and enhanced cellular oxidation. Redox signaling contributes to the plant response playing thioredoxins (TRXs) a central role. In this work we explore the potential contribution of Arabidopsis TRXo1 to the photosynthetic response under salinity analyzing Arabidopsis wild-type (WT) and two Attrxo1 mutant lines in their growth under short photoperiod and higher light intensity than previous reported works. Stomatal development and apertures and the antioxidant, hormonal and metabolic acclimation are also analyzed. In control conditions mutant plants displayed less and larger developed stomata and higher pore size which could underlie their higher stomatal conductance, without being affected in other photosynthetic parameters. Under salinity, all genotypes displayed a general decrease in photosynthesis and the oxidative status in the Attrxo1 mutant lines was altered, with higher levels of H2O2 and NO but also higher ascorbate/glutathione (ASC/GSH) redox states than WT plants. Finally, sugar changes and increases in abscisic acid (ABA) and NO may be involved in the observed higher stomatal response of the TRXo1-altered plants. Therefore, the lack of AtTRXo1 affected stomata development and opening and the mutants modulate their antioxidant, metabolic and hormonal responses to optimize their adaptation to salinity.

Long-term evaluation of the effect of peracetic acid on a mixed anoxic culture: Organic matter degradation, denitrification, and microbial community structure

The objective of this study was to assess the long-term effect of peracetic acid (PAA) solution on anoxic organic matter degradation and denitrification. Three bioreactors (R1, R2, and R3) were operated for 166 d, fed with poultry processing wastewater and gradually increased H2O2 (R2) or PAA solution (i.e., PAA + H2O2)(R3). Organic matter degradation, quantified as the extent of COD removal, and denitrification were assessed. COD removal and denitrification were not affected by H2O2 and PAA solutions added to the wastewater before feeding (indirect addition). However, both processes were significantly affected by high levels of H2O2 (i.e., 27 mg/L) and PAA solution (i.e., 60/8.4 mg/L PAA/H2O2) directly added to the reactors, but fast recovery was observed when direct addition of H2O2 and PAA solution ended. The negative impact on denitrification was the combined result of enzyme inhibition and loss of cell viability, both related to increased intracellular ROS levels. Partial acclimation to PAA solution took place during the long-term operation, resulting in higher denitrification activity, higher cell viability and lower intracellular ROS than in a short-term batch assay with one-time PAA addition. Microbiome analysis showed major shift in community composition during the long-term operation with PAA solution addition, but no significant shift after the long-term operation with H2O2 addition. Among the main denitrifying genera, Thauera and unclassified Chitinophagaceae were negatively impacted while Chryseobacterium and unclassified Enterobacteriaceae were enriched during the long-term operation with PAA addition.

Multifunctional nanozyme for multimodal imaging-guided enhanced sonodynamic therapy by regulating the tumor microenvironment.

Sonodynamic therapy (SDT) is a highly promising approach for cancer therapy, but its efficacy is severely hampered by the low specificity of sonosensitizers and the unfavorable characteristics of the tumor microenvironment (TME), such as hypoxia and glutathione (GSH) overexpression. To solve these problems, in this work, we encapsulated IR780 and MnO2 in PLGA and linked Angiopep-2 (Ang) to synthesize a multifunctional nanozyme (Ang-IR780-MnO2-PLGA, AIMP) to enhance SDT. With Ang functionalization to facilitate blood-brain barrier (BBB) penetration and glioma targeting, and through the function of IR780, these nanoparticles (NPs) showed improved targeting of cancer cells, especially mitochondria, and spread deep into tumor centers. Upon low-intensity focused ultrasound (LIFU) irradiation, reactive oxygen species (ROS) were produced and induced tumor cell apoptosis. Combined with the specific mitochondria-targeting ability of IR780, the sonodynamic effects were amplified because mitochondria are sensitive to ROS. In addition, MnO2 exhibited enzyme-like activity, reacting with the high levels of hydrogen protons (H+), H2O2 and GSH in the TME to continuously produce oxygen and consume GSH, which further enhanced the effect of SDT. Moreover, Mn2+ can be released in response to TME stimulation and used as a magnetic resonance (MR) contrast agent. In addition, IR780 has photoacoustic (PA)/fluorescence (FL) imaging capabilities. Our results demonstrated that AIMP NPs subjected to LIFU triggering maximally enhanced the therapeutic effect of SDT by multiple mechanisms, including multiple targeting, deep penetration, oxygen supply in situ and GSH depletion, thereby significantly inhibiting tumor growth and distal metastasis without systemic toxicity. In summary, this multifunctional nanozyme provides a promising strategy for cancer diagnosis and treatment under the intelligent guidance of multimodal imaging (PA/FL/MR) and may be a safe clinical translational method.

EVALUATION OF SALINITY STRESS EFFECTS ON CHANGES IN PHOTOSYNTHETIC PIGMENTS, HYDROGEN PEROXIDE AND OSMOLYTES IN SENSITIVE AND TOLERANT CULTIVARS OF WHEAT CROP

Investigation of wheat response to salinity stress can help to better understand the effective defense mechanisms of salinity stress tolerance. For this purpose, biochemical and physiological traits related to salinity tolerance in wheat cultivars were evaluated at Gorgan University of Agricultural Sciences and Natural Resources in 2019. Experimental factors, included two wheat crop cultivars (Sarc and Chinese spring as tolerant and susceptible wheat cultivars, respectively) and sampling time series (zero or control, 24, 48, 72, and 96 h) were examined in a factorial experiment based on a completely randomized design with three replications. Salinity stress was applied with sodium chloride at a concentration of 250 mM to uniform 10-day-old seedlings at the two-leaf stage, followed by sampling of shoot tissue. The studied traits were hydrogen peroxide (H2O2 ), chlorophyll a, chlorophyll b, total chlorophyll, chlorophyllase, carotenoids, proline, and total carbohydrates. Results of analysis of variance (ANOVA) indicated significant effects of genotype, time, and interaction of genotype × time (except H2O2 and total carbohydrates) on all the studied traits. Results of interaction of genotype × time showed although the trend of changes in the studied traits, depending on the type of cultivar and the sampling time were different, but generally, the susceptible Chinese spring cultivar contained higher levels of chlorophyllase and carotenoids than the control time at the end of sampling time and also higher H2O2 levels than the Sarc tolerant cultivar, while the Sarc tolerant cultivar, on the other hand, contained higher levels of chlorophyll a, chlorophyll b, total chlorophyll, and proline than the control time at the end of sampling time and also greater total carbohydrates than the susceptible Chinese spring cultivar. The results confirm the higher capacity of the antioxidant defense system of Sarc tolerant cultivar than the susceptible Chinese spring cultivar. Therefore

Activatable NIR-II Plasmonic Nanotheranostics for Efficient Photoacoustic Imaging and Photothermal Cancer Therapy.

Precise manipulation of optical properties through the structure-evolution of plasmonic nanoparticles is of great interest in biomedical fields including bioimaging and phototherapy. However, previous success has been limited to fixed assembled structures or visible-NIR-I absorption. Here, an activatable NIR-II plasmonic theranostics system based on silica-encapsulated self-assembled gold nanochains (AuNCs@SiO2 ) for accurate tumor diagnosis and effective treatment is reported. This transformable chain structure breaks through the traditional molecular imaging window, whose absorption can be redshifted from the visible to the NIR-II region owing to the fusion between adjacent gold nanoparticles in the restricted local space of AuNCs@SiO2 triggered by the high H2 O2 level in the tumor microenvironment (TME), leading to the generation of a new string-like structure with strong NIR-II absorption, which is further confirmed by finite-difference-time-domain (FDTD) simulation. With the TME-activated characteristics, AuNCs@SiO2 exhibits excellent properties for photoacoustic imaging and a high photothermal conversion efficiency of 82.2% at 1064nm leading to severe cell death and remarkable tumor growth inhibition in vivo. These prominent intelligent TME-responsive features of AuNCs@SiO2 may open up a new avenue to explore optical regulated nano-platform for intelligent, accurate, and noninvasive theranostics in NIR-II window.

Long-term evaluation of the effect of peracetic acid on a mixed aerobic culture: Organic matter degradation, nitrification, and microbial community structure

Peracetic acid (PAA) has been widely used as a disinfectant in many industries; its use in poultry processing is steadily increasing. However, information related to the potential inhibitory effect of PAA solutions (PAA and H2O2) on biological wastewater treatment processes used by the poultry processing industry is extremely limited. The work reported here assessed the long-term effect of PAA solution on aerobic degradation and nitrification in three bioreactors fed with poultry processing wastewater by quantifying the extent of COD removal and nitrification rates. Changes in culture viability, intracellular reactive oxygen species (ROS), and microbial community structure were also evaluated. COD removal and nitrification were not affected by H2O2 and PAA solutions added to the wastewater before feeding (indirect addition). However, both processes were significantly affected by high levels of H2O2 (i.e., 27 mg/L) and PAA solution (i.e., 60/8.4 mg/L PAA/H2O2) directly added to the reactors. Directly added PAA/H2O2 at 40/5.6 mg/L was the lowest dose resulting in nitrification inhibition. Fast recovery of COD removal and nitrification was observed when direct addition of H2O2 and PAA solution ended. Cell viability measurements revealed that the negative impact on nitrification was predominantly attributed to enzyme inhibition rather than to loss of cell viability. The impact on nitrification was not related to intracellular ROS levels. Microbiome analysis showed major shifts in community composition during the long-term addition of H2O2 and even more with PAA addition. No significant time-trend change in the relative abundance of ammonia-oxidizing bacteria or nitrite-oxidizing bacteria was observed, further supporting the conclusion that the negative impact on nitrification was attributed mainly to enzyme inhibition.

Loss function of SL (sekiguchi lesion) in the rice cultivar Minghui 86 leads to enhanced resistance to (hemi)biotrophic pathogens

BackgroundSerotonin, originally identified as a neurotransmitter in mammals, functions as an antioxidant to scavenge cellular ROS in plants. In rice, the conversion of tryptamine to serotonin is catalyzed by SL (sekiguchi lesion), a member of cytochrome P450 monooxygenase family. The sl mutant, originated from rice cultivar Sekiguchi-asahi, exhibits spontaneous lesions, whereas its immune responses to pathogens have not been clearly characterized.ResultsHere we identified three allelic mutants of SL in an indica rice restore line Minghui 86 (MH86), named as sl-MH-1, − 2 and − 3, all of which present the typical lesions under normal growth condition. Compared with those in MH86, the serotonin content in sl-MH-1 is dramatically decreased, whereas the levels of tryptamine and L-trytophan are significantly increased. The sl-MH-1 mutant accumulates high H2O2 level at its lesion sites and is more sensitive to exogenous H2O2 treatment than the wild type. When treated with the reductant vitamin C (Vc), the lesion formation on sl-MH-1 leaves could be efficiently suppressed. In addition, sl-MH-1 displayed more resistant to both the blast fungus and blight bacteria, Pyricularia oryzae (P. oryzae, teleomorph: Magnaporthe oryzae) and Xanthomonas oryzae pv. Oryzae (Xoo), respectively. The pathogen-associated molecular patterns (PAMPs)-triggered immunity (PTI) responses, like reactive oxygen species (ROS) burst and callose deposition, were enhanced in sl-MH-1. Moreover, loss function of SL resulted in higher resting levels of the defense hormones, salicylic acid and jasmonic acid. The RNA-seq analysis indicated that after P. oryzae infection, transcription of the genes involved in reduction-oxidation regulation was the most markedly changed in sl-MH-1, compared with MH86.ConclusionsOur results indicate that SL, involving in the final step of serotonin biosynthesis, negatively regulates rice resistance against (hemi)biotrophic pathogens via compromising the PTI responses and defense hormones accumulation.

E3 ligase, the Oryza sativa salt-induced RING finger protein 4 (OsSIRP4), negatively regulates salt stress responses via degradation of the OsPEX11-1 protein.

OsSIRP4 is an E3 ligase that acts as a negative regulator in the plant response to salt stress via the 26S proteasomal system regulation of substrate proteins, OsPEX11-1, which it provides important information for adaptation and regulation in rice. Plants are sessile organisms that can be exposed to environmental stress. Plants alter their cellular processes to survive under potentially unfavorable conditions. Protein ubiquitination is an important post-translational modification that has a crucial role in various cellular signaling processes in abiotic stress response. In this study, we characterized Oryza sativa salt-induced RING finger protein 4, OsSIRP4, a membrane and cytosol-localized RING E3 ligase in rice. OsSIRP4 transcripts were highly induced under salt stress in rice. We found that OsSIRP4 possesses E3 ligase activity; however, no E3 ligase activity was observed with a single amino acid substitution (OsSIRP4C269A). The results of the yeast two hybrid system, in vitro pull-down assay, BiFC analysis, in vitro ubiquitination assay, and in vitro degradation assay indicate that OsSIRP4 regulates degradation of a substrate protein, OsPEX11-1 (Oryza sativa peroxisomal biogenesis factor 11-1) via the 26S proteasomal system. Phenotypic analysis of OsSIRP4-overexpressing plants demonstrated hypersensitivity to salt response compared to that of the wild type and mutated OsSIRP4C269A plants. In addition, OsSIRP4-overexpressing plants exhibited significant low enzyme activities of superoxide dismutase, catalase, and peroxidase, and accumulation of proline and soluble sugar, but a high level of H2O2. Furthermore, qRT data on transgenic plants suggest that OsSIRP4 acted as a negative regulator of salt response by diminishing the expression of genes related to Na+/K+ homeostasis (AtSOS1, AtAKT1, AtNHX1, and AtHKT1;1) in transgenic plants under salt stress. These results suggest that OsSIRP4 plays a negative regulatory role in response to salt stress by modulating the target protein levels.

Chronic exposure of hydrogen peroxide alters redox state, apoptosis and endoplasmic reticulum stress in common carp (Cyprinus carpio)

Hydrogen peroxide (H2O2) appears to be ubiquitous in natural water. Higher level of H2O2 can cause physiological stress, immunosuppression and even death in aquatic animals, but the physiological and molecular mechanisms of H2O2 toxicity are not well studied. Thus, the aim of the present study was to exposure potential toxic mechanisms of H2O2 via assessing the effects on redox state, apoptosis and endoplasmic reticulum (ER) stress in common carp. The fish were subjected to four concentrations of H2O2 (0, 0.25, 0.5 and 1 mM) for 14 days. And then, the tissues including blood, liver, muscle, gills, intestines, heart, kidney and spleen were collected to measure biochemical parameter and gene expression. The results showed that H2O2 exposure suppressed the majority antioxidative parameters in serum, liver, muscle and intestines, but enhanced T-SOD, CAT and T-AOC levels in gills. In all tested tissues, the MDA content was significantly promoted by H2O2 exposure. The oxidative stress-related genes including nrf2, gstα, sod, cat and/or gpx1 were upregulated in liver, gills, muscle, intestines, and/or kidney, but downregulated in heart after H2O2 exposure. Moreover, the ho-1 mRNA level was inhibited by H2O2 exposure in all tissues except intestines and spleen. After 14 days of exposure, H2O2 induced ER stress and initiated IRE1 and PERK pathways, which activated downstream genes, including chop, grp78 and/or xbp1s, to regulate UPR in liver, gills, muscle and/or heart. Meanwhile, H2O2 exposure activated MAPK pathway to regulate mitochondria-related genes including bcl-2, bax and cytc, which further triggered cas-8, cas-9 and cas-3, and accelerated apoptosis in liver, gills, muscle and heart. Importantly, in different tissues, the genes associated with oxidative stress, ER stress and apoptosis showed a different influence, and more significant influence was observed in the muscle, gills and liver. Overall results suggested that long-term H2O2 exposure induced oxidative stress, ER stress and apoptosis in the majority of tested tissues of common carp. The Nrf2, IRE1, PERK and MAPK pathways played important roles in H2O2-induced toxicity in fish. These data enriched the toxicity mechanism of H2O2 in fish, which might contribute to the risk assessment of H2O2 in aquatic environment.

H2O2 and Engrailed 2 paracrine activity synergize to shape the zebrafish optic tectum

Although a physiological role for redox signaling is now clearly established, the processes sensitive to redox signaling remains to be identified. Ratiometric probes selective for H2O2 have revealed its complex spatiotemporal dynamics during neural development and adult regeneration and perturbations of H2O2 levels disturb cell plasticity and morphogenesis. Here we ask whether endogenous H2O2 could participate in the patterning of the embryo. We find that perturbations of endogenous H2O2 levels impact on the distribution of the Engrailed homeoprotein, a strong determinant of midbrain patterning. Engrailed 2 is secreted from cells with high H2O2 levels and taken up by cells with low H2O2 levels where it leads to increased H2O2 production, steering the directional spread of the Engrailed gradient. These results illustrate the interplay between protein signaling pathways and metabolic processes during morphogenetic events.

Doxifluridine-based pharmacosomes delivering miR-122 as tumor microenvironments-activated nanoplatforms for synergistic treatment of hepatocellular carcinoma

A novel kind of anti-cancer pharmacosome (named NPC-D) derived from Doxifluridine (5′-DFUR) was described, which could be activated by tumor microenvironments (TMEs). The NPC-D with H2O2-sensitive linker was dispersed well in water and simultaneously interacted with nucleic acids including plasmids encoding miR-122 (p122) and EpCAM-targeted aptamer (ap1) via charge interaction and hydrogen bonding. The integrated nanosystem (p122-ap1@NPC-D) was found to unleash by programmed TMEs (high level of H2O2 and low pH) to efficiently transfect miR-122 into MHCC-LM3 cells, followed by the releases of 5-FU. Besides, p122-ap1@NPC-D significantly countered the chemotherapy resistance and played a synergistic effect. These unique nanoparticles dramatically enhanced the anti-proliferation, and modulated the cellular apoptosis by the down-regulation of various signal pathways which imparted a bright application prospect in HCC treatment.

Proteomic and metabolic profile analysis of low-temperature storage responses in Ipomoea batata Lam. tuberous roots

BackgroundSweetpotato (Ipomoea batatas L.) is one of the seven major food crops grown worldwide. Cold stress often can cause protein expression pattern and substance contents variations for tuberous roots of sweetpotato during low-temperature storage. Recently, we developed proteometabolic profiles of the fresh sweetpotatoes (cv. Xinxiang) in an attempt to discern the cold stress-responsive mechanism of tuberous root crops during post-harvest storage.ResultsFor roots stored under 4 °C condition, the CI index, REC and MDA content in roots were significantly higher than them at control temperature (13 °C). The activities of SOD, CAT, APX, O2.- producing rate, proline and especially soluble sugar contents were also significantly increased. Most of the differentially expressed proteins (DEPs) were implicated in pathways related to metabolic pathway, especially phenylpropanoids and followed by starch and sucrose metabolism. L-ascorbate peroxidase 3 and catalase were down-regulated during low temperature storage. α-amylase, sucrose synthase and fructokinase were significantly up-regulated in starch and sucrose metabolism, while β-glucosidase, glucose-1-phosphate adenylyl-transferase and starch synthase were opposite. Furthermore, metabolome profiling revealed that glucosinolate biosynthesis, tropane, piperidine and pyridine alkaloid biosynthesis as well as protein digestion and absorption played a leading role in metabolic pathways of roots. Leucine, tryptophan, tyrosine, isoleucine and valine were all significantly up-regulated in glucosinolate biosynthesis.ConclusionsOur proteomic and metabolic profile analysis of sweetpotatoes stored at low temperature reveal that the antioxidant enzymes activities, proline and especially soluble sugar content were significantly increased. Most of the DEPs were implicated in phenylpropanoids and followed by starch and sucrose metabolism. The discrepancy between proteomic (L-ascorbate peroxidase 3 and catalase) and biochemical (CAT/APX activity) data may be explained by higher H2O2 levels and increased ascorbate redox states, which enhanced the CAT/APX activity indirectly. Glucosinolate biosynthesis played a leading role in metabolic pathways. Leucine, tryptophan, tyrosine, isoleucine and valine were all significantly up-regulated in glucosinolate biosynthesis.

Implantable Bioresponsive Nanoarray Enhances Postsurgical Immunotherapy by Activating Pyroptosis and Remodeling Tumor Microenvironment

AbstractDespite the potential of drug‐loaded scaffolds for tumor recurrence and metastasis (TRM) postoperation, their therapeutic benefits are limited by marked immunosuppressive tumor microenvironment (ITME) and drug‐related untargeted toxicity. Herein, an innovative implantable bioresponsive nanoarray is developed to overcome the above limitations. Chemotherapeutics doxorubicin (DOX) and the epigenetic modulator JQ1 are coloaded into tumor‐targeting nanoparticles (HP‐DOX/JQ1 NPs), which are then linked up through a bio‐responsive linker to construct the nanoarray loading with another part of JQ1 (DOX/JQ1‐IBRN). Under high level of H2O2 in TME, the implanted DOX/JQ1‐IBRN disaggregates and release JQ1 while generating small‐sized HP‐DOX/JQ1 NPs for realizing ITME modulation and tumor‐targeting therapy. JQ1 selectively blocks programmed death‐ligand 1 (PD‐L1) mediated immune evasion and reduces regulatory T cells (Tregs)/‐disruptive effect to facilitate immunopositivity. HP‐DOX/JQ1 NPs destroy residual tumor precisely and trigger gasdermin E (GSDME)‐dependent pyroptosis, further enhancing the number and functions of tumor‐infiltrating T lymphocytes for antitumor immunity. It is demonstrated that DOX/JQ1‐IBRN prevents post‐surgical TRM and prolongs survival in multiple murine tumor models with negligible toxicity. This cooperation in tumor accurate pyroptosis and ITME conversion through the implantable nanoarray (a simple, valid, and safe scaffold) is expected to provide crucial insights for post‐surgical treatment.

Quercetin treatment increases H2O2 removal by restoration of endogenous antioxidant activity and blocks isoproterenol-induced cardiac hypertrophy.

Oxidative stress, characterized by the accumulation of reactive oxygen species (ROS), is implicated in the pathogenesis of several diseases, including cardiac hypertrophy. The flavonoid quercetin is a potent ROS scavenger, with several beneficial effects for the cardiovascular system, including antihypertrophic effects. Oxidative imbalance has been implicated in cardiac hypertrophy and heart failure. In this work, we tested whether quercetin could attenuate cardiac hypertrophy by improving redox balance and mitochondrial homeostasis. To test this hypothesis, we treated a group of mice with isoproterenol (30mg/kg/day) for 4 or 8 consecutive days. Another group received quercetin (10mg/kg/day) from day 5th of isoproterenol treatment. We carried out the following assays in cardiac tissue: measurement of cardiac hypertrophy, protein sulfhydryl, catalase, Cu/Zn and Mn-superoxide dismutase (SOD) activity, detection of H2O2, and opening of the mitochondrial permeability transition pore. The animals treated with isoproterenol for the initial 4days showed increased cardiac weight/tibia length ratio, decreased protein sulfhydryl content, compromised SOD and catalase activity, and high H2O2 levels. Quercetin was able to attenuate cardiac hypertrophy, restore protein sulfhydryl, and antioxidant activity, in addition to efficiently blocking the H2O2. We also observed that isoproterenol decreases mitochondrial SOD activity, while quercetin reverses it. Strikingly, quercetin also protects mitochondria against the opening of mitochondrial permeability transition pore. Taken together, these results suggest that quercetin is capable of reversing established isoproterenol-induced cardiac hypertrophy through the restoration of cellular redox balance and protecting mitochondria.

Synergistic in-situ growth of silver nanoparticles with nanozyme activity for dual-mode biosensing and cancer theranostics

A multifunctional nanocomposite of AgNPs@GQDs is prepared by synergistic in-situ growth of silver nanoparticles (AgNPs) on the complex of tannic acid (TA) and graphene quantum dots (GQDs) for the construction of dual-mode biosensing platform and cancer theranostics. The nanocomposite exhibits a hydrogen peroxide (H2O2)-responsive degradation, in which Ag0 is oxidized to Ag+ along with the release of oxidized TA and GQDs. The degradation induces the decreased absorbance and enhanced fluorescence (FL) intensity due to the suppression of Förster resonance energy transfer (FRET) in AgNPs@GQDs, which is employed for colorimetric/fluorescence dual-mode sensing of H2O2. The intrinsic peroxidase-like activity of GQDs nanozyme can effectively catalyze the oxidation reaction, enhancing the detection sensitivity significantly. Based on the generation of H2O2 from the oxidation of glucose with the catalysis of glucose oxidase (GOx), this nanoprobe is versatilely used for the determination of glucose in human serum. Further, through combining the H2O2-responsive degradation of AgNPs@GQDs with high H2O2 level in cancer cells, the nanocomposites exhibit good performance in cancer cell recognition and therapy, in which the synergistic anticancer effect of Ag+ and oxidized TA contribute to effective cell death, and the liberated GQDs are used to monitor the therapeutic effect by cell imaging.

Dissipation of pyridaphenthion by cyanobacteria: Insights into cellular degradation, detoxification and metabolic regulation

Excessive use of organophosphorus pesticides such as pyridaphenthion (PY) to constrain insects induced crop loss, results in soil and water sources contamination. Cyanobacteria are sensitive biological indicators and promising tools for bioremediation of soil and water pollutants. To understand PY toxicity, detoxification and degradation in cyanobacteria, we performed a comparative study in the two diazotrophic cyanobacteria; Anabaena laxa and Nostoc muscorum. They were exposed to mild (5 mg/L) and high (10 mg/L) concentrations of PY for 7 days. Compared to A. laxa, N. muscorum efficiently showed high PY accumulation and degradation to a safe environmentally product; 6-hydroxy-2-phenylpyridazin-3(2 H)-one. PY inhibited cell growth and reduced Chl a content and photosynthesis related enzymes (PEPC and RuBisCo) activities in both species, but to less extend in N. muscorum. It also induced oxidative damage, particularly in A. laxa, as indicated by high H2O2, lipid peroxidation and protein oxidation levels and increased NADPH oxidase enzyme activity. N. muscorum invested more in antioxidants induction, i.e., induced ascorbate and glutathione cycle, however, these antioxidants increments in A. laxa were less pronounced. Overall, this study provides more in-deep insights into the PY toxicity and the role of N. muscorum as a promising PY remediator.

Nanoreactor of “butterfly effect” inciting a triple interlocked combination of starvation/chemo/metal ion therapy by remodeling tumor microenvironment

Tumor microenvironment has been used as the driving force of nano-therapy systems. However, due to its own complexity and heterogeneity, the therapeutic effects of many systems are still hindered by inherent cellular barriers. Herein, we designed a biodegradable nanoreactor showing interlocking “butterfly effect”, which reconstructed the tumor microenvironment (TME) by functional “butterfly” and initiated the next cascade reaction to enhance the efficacy. The silver nanocubes (Ag NCs) as the core, then loading polydopamine (PDA), glucose oxidase (GOx), and tirapazamine (TPZ), which was further disguised by tumor cytomembrane to construct as a bionic nanoreactor Ag@PDA/GOx/TPZ@M (APGTM). When the nanoreactors were homologously targeted to the tumor site, GOx as the “butterfly” caused the tumor cells entering starvation state by consuming glucose and O2 and generating gluconate and H2O2. Furtherly, the generated hypoxia state activated TPZ to achieve chemotherapy, and the non-toxic Ag NCs were degraded into toxic Ag+ under high H2O2 levels to carry out metal ions therapy. This “butterfly effect” of nanoreactor launching a triplet chain reaction can solve the problem of the lack of reciprocity on multi-modal therapy by reshaped the TME, which opens a new way for accurate and effective tumor cell ablation.

Potential Role of Photosynthesis in the Regulation of Reactive Oxygen Species and Defence Responses to Blumeria graminis f. sp. tritici in Wheat.

Photosynthesis is not only a primary generator of reactive oxygen species (ROS) but also a component of plant defence. To determine the relationships among photosynthesis, ROS, and defence responses to powdery mildew in wheat, we compared the responses of the Pm40-expressing wheat line L658 and its susceptible sister line L958 at 0, 6, 12, 24, 48, and 72 h post-inoculation (hpi) with powdery mildew via analyses of transcriptomes, cytology, antioxidant activities, photosynthesis, and chlorophyll fluorescence parameters. The results showed that H2O2 accumulation in L658 was significantly greater than that in L958 at 6 and 48 hpi, and the enzymes activity and transcripts expression of peroxidase and catalase were suppressed in L658 compared with L958. In addition, the inhibition of photosynthesis in L658 paralleled the global downregulation of photosynthesis-related genes. Furthermore, the expression of the salicylic acid-related genes non-expressor of pathogenesis related genes 1 (NPR1), pathogenesis-related 1 (PR1), and pathogenesis-related 5 (PR5) was upregulated, while the expression of jasmonic acid- and ethylene-related genes was inhibited in L658 compared with L958. In conclusion, the downregulation of photosynthesis-related genes likely led to a decline in photosynthesis, which may be combined with the inhibition of peroxidase (POD) and catalase (CAT) to generate two stages of H2O2 accumulation. The high level of H2O2, salicylic acid and PR1 and PR5 in L658 possible initiated the hypersensitive response.

Neutrophil to lymphocyte ratio and breast cancer risk: analysis by subtype and potential interactions

Multiple studies have found the neutrophil to lymphocyte ratio (NLR) to be associated with adverse breast cancer (BC) prognosis and survival. Very limited data exist on the role of NLR and risk of BC. The BREOGAN study is a population-based case–control study conducted in Galicia, Spain. We examined the WBC- and NLR-BC relationships. The risk of BC increased with increasing levels of neutrophils percentage (NE%) (multivariable OR for the highest category (95% CI) = 2.14 (1.39–3.32), P-trend < 0.001) and of the NLR (multivariable OR for the highest category (95% CI) = 1.93 (1.26–2.97), P-trend < 0.001). Lymphocytes absolute (L#) and percentage (L%) were associated with a decreased risk of BC (multivariable OR for the highest category (95% CI) = 0.54 (0.35–0.83), and 0.51 (0.33–0.79), P-trend = 0.001 and < 0.001, respectively). The NLR-BC association was more pronounced among Luminal A BC (multivariable OR for the highest category (95% CI) = 2.00 (1.17–3.45), P-trend < 0.001), HER2-negative BC (multivariable OR for the highest category (95% CI) = 1.87 (1.16–3.02), P-trend < 0.001), and those with high total cholesterol and low H2O2 levels.

Reactive Oxygen Species (ROS) Metabolism and Nitric Oxide (NO) Content in Roots and Shoots of Rice (Oryza sativa L.) Plants under Arsenic-Induced Stress

Arsenic (As) is a highly toxic metalloid for all forms of life including plants. Rice is the main food source for different countries worldwide, although it can take up high amounts of As in comparison with other crops, showing toxic profiles such as decreases in plant growth and yield. The induction of oxidative stress is the main process underlying arsenic toxicity in plants, including rice, due to an alteration of the reactive oxygen species (ROS) metabolism. The aim of this work was to gain better knowledge on how the ROS metabolism and its interaction with nitric oxide (NO) operate under As stress conditions in rice plants. Thus, physiological and ROS-related biochemical parameters in roots and shoots from rice (Oryza sativa L.) were studied under 50 μM arsenate (AsV) stress, and the involvement of the main antioxidative systems and NO in the response of plants to those conditions was investigated. A decrease of 51% in root length and 27% in plant biomass was observed with 50 μM AsV treatment, as compared to control plants. The results of the activity of superoxide dismutase (SOD) isozymes, catalase, peroxidase (POD: total and isoenzymatic), and the enzymes of the ascorbate–glutathione cycle, besides the ascorbate and glutathione contents, showed that As accumulation provoked an overall significant increase of most of them, but with different profiles depending on the plant organ, either root or shoot. Among the seven identified POD isozymes, the induction of the POD-3 in shoots under As stress could help to maintain the hydrogen peroxide (H2O2) redox homeostasis and compensate the loss of the ascorbate peroxidase (APX) activity in both roots and shoots. Lipid peroxidation was slightly increased in roots and shoots from As-treated plants. The H2O2 and NO contents were enhanced in roots and shoots against arsenic stress. In spite of the increase of most antioxidative systems, a mild oxidative stress situation appears to be consolidated overall, since the growth parameters and those from the oxidative damage could not be totally counteracted. In these conditions, the higher levels of H2O2 and NO suggest that signaling events are simultaneously occurring in the whole plant.