Bioorthogonal microglia-inspired mesenchymal stem cell bioengineering system creates livable niches for enhancing ischemic stroke recovery via the hormesis.

Mesenchymal stem cells (MSCs) experience substantial viability issues in the stroke infarct region, limiting their therapeutic efficacy and clinical translation. High levels of deadly reactive oxygen radicals (ROS) and proinflammatory cytokines (PC) in the infarct milieu kill transplanted MSCs, whereas low levels of beneficial ROS and PC stimulate and improve engrafted MSCs' viability. Based on the intrinsic hormesis effects in cellular biology, we built a microglia-inspired MSC bioengineering system to transform detrimental high-level ROS and PC into vitality enhancers for strengthening MSC therapy. This system is achieved by bioorthogonally arming metabolic glycoengineered MSCs with microglial membrane-coated nanoparticles and an antioxidative extracellular protective layer. In this system, extracellular ROS-scavenging and PC-absorbing layers effectively buffer the deleterious effects and establish a micro-livable niche at the level of a single MSC for transplantation. Meanwhile, the infarct's inanimate milieu is transformed at the tissue level into a new living niche to facilitate healing. The engineered MSCs achieved viability five times higher than natural MSCs at seven days after transplantation and exhibited a superior therapeutic effect for stroke recovery up to 28 days. This vitality-augmented system demonstrates the potential to accelerate the clinical translation of MSC treatment and boost stroke recovery.

Effects of low concentration of gallic acid on the growth and microcystin production of Microcystis aeruginosa.

Gallic acid (GA) is an allelochemical that has been utilized in high concentrations for the management of harmful algal blooms (HABs). However, there is limited knowledge regarding its impact on the growth of M. aeruginosa as the GA concentration transitions from high to low during the HABs control process. This study has revealed that as the GA concentration decreases (from 10 mg/L to 0.001 µg/L), a dose-response relationship becomes apparent in the growth of M. aeruginosa and microcystin production, characterized by high-dose inhibition and low-dose stimulation. Notably, at the concentration of 0.1 µg/L GA, the most significant growth-promoting effect on both growth and MCs synthesis was observed. The growth rate and maximum cell density were increased by 1.09 and 1.16 times, respectively, compared to those of the control group. Additionally, the contents of MCs synthesis saw a remarkable increase, up by 1.85 times. Furthermore, lower GA concentrations stimulated the viability of cyanobacterial cells, resulting in substantially higher levels of reactive oxygen species (ROS) and chlorophyll-a (Chl a) compared to other concentrations. Most importantly, the expression of genes governing MCs synthesis was significantly upregulated, which appears to be the primary driver behind the significantly higher MCs levels compared to other conditions. The ecological risk quotient (RQ) value of 0.1 µg/L GA was the highest of all experimental groups, which was approximately 30 times higher than that of the control, indicating moderate risk. Therefore, it is essential to pay attention to the effect of M. aeruginosa growth, metabolism and water ecological risk under the process of reducing GA concentration after dosing during the HABs control process.

Dosage impact of submerged plants extracts on Microcystis aeruginosa growth: From hormesis to inhibition.

Allelopathy has been demonstrated to be an environmentally friendly way to control harmful algal blooms. Allelochemicals of submerged plants have attracted extensive research due to their bioavailability. The dose-response of submerged plant extracts on algae growth is worth further study to improve the efficiency of bioremediation. In this study, the ultrasonic-enzymatic assistance method was utilized to extract allelochemicals from Ceratophyllum, Myriophyllum spicatum, and Vallisneria. The effects of low-dosage and high-dosage extracts on the growth of Microcystis aeruginosa were compared based on cell biomass and morphology, photosynthetic parameters, reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels. The results showed that the three submerged plant extracts exhibited hormetic effects at low dosages and inhibitory effects at high dosages on algal growth. Within 48 h of cultivation, the enzymatic activities of Microcystis aeruginosa fluctuated, suggesting that the extracts of the three submerged plants induced different oxidative reactions. After 120 h of cultivation with high-dosage extracts, the physiological and biochemical reactions of Microcystis aeruginosa significantly decreased, indicating the effectiveness of the allelopathy of Ceratophyllum, Myriophyllum spicatum, and Vallisneria extracts in controlling algal blooms. The phenomenon of hormesis and inhibition effect confirmed a significant dose-response relationship between the allelochemicals of submerged plant extracts and Microcystis aeruginosa, which could be attributed to the composition and content of allelochemicals. These findings highlight the importance of the relative concentration of the biological algaecide and will benefit other researchers in determining the safe dosage of plant allelochemicals when used in water.

Effect of ibuprofen on the sulfur autotrophic denitrification process and microbial toxic response mechanism.

The effect of ibuprofen (IBU) on the sulfur autotrophic denitrification (SAD) process and microbial toxic response mechanism were investigated. Nitrate removal performance was inhibited by high IBU concentrations (10 and 50 mg/L), and the effect of low IBU concentrations (1 mg/L) on nitrate removal performance was negligible. The low IBU concentration induced basal oxidative stress for microbial self-protection, while the high IBU concentration induced high-intensity oxidative stress to damage the microbial cell membrane structure. Electrochemical characterization showed that the low IBU concentration stimulated the electron transfer efficiency, which was inhibited at the high IBU concentration. Moreover, the variation content of nicotinamide adenine dinucleotide (NADH) and nitrate reductase showed that metabolic activity increased at low IBU concentrations and decreased at high IBU concentrations during the sulfur autotrophic nitrate reduction process. This study proposed the hormesis toxic response mechanism of the SAD process to IBU exposure.

Low-level cadmium exposure induced hormesis in peppermint young plant by constantly activating antioxidant activity based on physiological and transcriptomic analyses.

As one of the most toxic environmental pollutants, cadmium (Cd) has lastingly been considered to have negative influences on plant growth and productivity. Recently, increasing studies have shown that low level of Cd exposure could induce hormetic effect which benefits to plants. However, the underlying mechanisms of Cd-triggered hormesis are poorly understood. In this study, we found that Cd stress treatment showed a hormetic effect on peppermint and Cd treatment with 1.6 mg L-1 concertation manifested best stimulative effects. To explore the hormesis mechanisms of Cd treatment, comparative transcriptome analysis of peppermint young plants under low (1.6 mg L-1) and high (6.5 mg L-1) level of Cd exposure at 0 h, 24 h and 72 h were conducted. Twelve of differentially expressed genes (DEGs) were selected for qRT-PCR validation, and the expression results confirmed the credibility of transcriptome data. KEGG analysis of DEGs showed that the phenylpropanoid biosynthesis and photosynthesis were important under both low and high level of Cd treatments. Interestingly, GO and KEGG analysis of 99 DEGs specifically induced by low level of Cd treatment at 72 h indicated that these DEGs were mainly involved in the pathway of phenylpropanoid biosynthesis and their functions were associated with antioxidant activity. The expression pattern of those genes in the phenylpropanoid biosynthesis pathway and encoding antioxidant enzymes during 72 h of Cd exposure showed that low level of Cd treatment induced a continuation in the upward trend but high level of Cd treatment caused an inverted V-shape. The changes of physiological parameters during Cd exposure were highly consistent with gene expression pattern. These results strongly demonstrate that low level of Cd exposure constantly enhanced antioxidant activity of peppermint to avoid oxidative damages caused by Cd ion, while high level of Cd stress just induced a temporary increase in antioxidant activity which was insufficient to cope with lasting Cd toxicity. Overall, the results presented in this study shed a light on the underlying mechanisms of the Cd-mediated hormesis in plant. Moreover, our study provided a safe method for the efficient utilization of mild Cd-contaminated soil as peppermint is an important cash plant.

Regulatory actions of rare earth elements (La and Gd) on the cell cycle of root tips in rice seedlings (Oryza sativa L.).

The continuous expansion of the application of rare earth elements (REEs) in various fields has attracted attention to their biosafety. At present, the molecular mechanisms underlying the biological effects of REEs are unclear. In this study, the effects of lanthanum (La) and gadolinium (Gd) on cell cycle progression in the root tips of rice seedlings were investigated. Low concentrations of REEs (0.1 mg L-1) induced an increase in the number of cells in the prophase and metaphase, while high concentrations of REEs (10 mg L-1) induced an increase in the number of cells in the late and terminal stages of the cell cycle, and apoptosis or necrosis. Additionally, low concentrations of REEs induced a significant increase in the expression of the cell cycle factors WEE1, CDKA;1, and CYCB1;1, and promoted the G2/M phase and accelerated root tip growth. However, at high REEs concentrations, the DNA damage response sensitized by BRCA1, MRE11, and TP53 could that prevent root tip growth by inhibiting the transcription factor E2F, resulting in obvious G1/S phase transition block and delayed G2/M phase conversion. Furthermore, by comparing the biological effect mechanisms of La and Gd, we found that these two REEs share regulatory actions on the cell cycle of root tips in rice seedlings.

Can 2,4-D promote the hormesis effect in upland rice?

This study aimed to evaluate the influence of low doses of 2,4-D on the agronomic traits of upland rice applied at different stages of crop growth. The work was carried out in a randomized completly blocks, and consisted of the application of 5 low doses of the 2,4-D herbicide (0, 0.68, 1.36, 2.04, 3.40 and 5.44 g acid equivalent (e.a.) ha-1) in two stages of rice development (tillering and floral differentiation). Nitrogen contentes in leaves, SPAD index and yield are higher when low doses of 2,4-D is applied in the tillering stage. Application of 2,4-D at a dose of 2.04 g a.e ha-1 results in a 19% increase in the number of spikelet per panicle. On the other hand, there is no effect of the application of low doses of 2,4-D on height, number of stems, active tillering and weight of 100 seeds. Our results contribute to increase knowledge of the hormesis effect in plants in order to increase crop yield.

Macrophage polarization induced by quinolone antibiotics at environmental residue level.

Widespread use of quinolone antibiotics leads to serious residues in the environment and toxicity effects. This paper studied the effects of three typical quinolone antibiotics ciprofloxacin, norfloxacin and pipemidic acid on the polarization of macrophages RAW264.7 cells. The experimental concentrations were 0.01, 0.1, 1, 10, 100 and 1000 µg/L according to the environmental residual level. By MTT assay, phagocytosis assay and migration assay, macrophages were found to exhibit hormesis effect of low dose promotion and high dose inhibition. The detection of macrophages surface markers showed that 0.1 µg/L antibiotics increased the secretion of pro-inflammatory cytokines and induced macrophages to be M1-type, and 1000 µg/L antibiotics significantly increased the secretion of anti-inflammatory cytokines and induced macrophages to be M2-type. In order to explore the relationship between low-dose excitatory effects and polarization, the mechanism of 0.1 µg/L antibiotics inducing macrophages to M1-type was further studied. Results showed that 0.1 µg/L quinolone antibiotics activated the key proteins in the PI3K/Akt, Notch1, JNK and JAK2/STAT3 signaling pathways to cause the secretion of pro-inflammatory cytokines and induce inflammation. In order to eliminate inflammation, macrophages number feedback increased, phagocytosis and migration function enhanced, showing hormesis effect. In vitro macrophages experiment confirmed that quinolone antibiotics with environmental residual concentration had immunotoxicity.

Hormesis of 2,4-D choline salt in productive aspects of cotton.

The stimulating effect of a low dose of a substance considered to be toxic is known as hormesis. The aim of this work was to use dose-response curves to evaluate the hormesis effect provided by sub-doses of the herbicide 2,4-D choline salt on the productivity of cotton at different phenological stages. The experimental design was based on randomized blocks, with four repetitions and the treatments were distributed in a 9x3 factorial design, with nine fractions of the mean label dose of the herbicide 2,4-D choline salt formulation (0 (control); 0.4275; 0.855; 1.71; 3.42; 8.55; 17.1; 34.2 and 68.4 g a.e. ha-1) associated with three different phenological stage of cotton, namely: V4, B4 and C4. The plants were evaluated as to the main productive parameters of the cotton plant. When applied at the V4 stage, sub-doses of the herbicide 2,4-D choline salt negatively affect the cotton crop. Sub-doses between 0.82 and 2.23 g a.e. ha-1 of the herbicide 2,4-D choline salt applied at the B4 stage of cotton can increase all the productive variables of the crop. The productive aspects of cotton plants in the C4 stage were not influenced by the application of sub-doses of 2,4-D choline salt.

Low concentrations of FA exhibits the Hormesis effect by affecting cell division and the Warburg effect.

Formaldehyde (FA), a ubiquitous indoor environmental pollutant, has been classified as a carcinogen. There are many studies showed that low levels of FA could promote cell proliferation, however, little is known about the signal pathways. To determine the potential molecular mechanisms, human chronic myeloid leukemia cells (K562 cells) and human bronchial epithelial cells (16HBE cells) were exposed to different concentrations of FA. The data showed that FA at 0-125 µM or 0-60 µM promoted the proliferation of K562 cells or 16HBE cells respectively, indicating that FA did have the Hormesis effect. FA at 75 µM (K562 cells) and 40 µM (16HBE cells) significantly promoted cell proliferation, increased intracellular reactive oxygen species (ROS) levels, and decreased glutathione (GSH) content. At the same time, FA treatment induced a marked increase in the key molecules of cell division like CyclinD-cdk4 and E2F1. In addition, pyruvate kinase isozyme M2 (PKM2), glucose, glucose transporter 1 (GLUT1), lactic acid and lactate dehydrogenase A (LDHA) content in the Warburg effect were increased. Administering Vitamin E (VE), significantly disrupted cell division and disturbed the Warburg effect, effectively indicating the decrease of cell activity. Conclusively, these findings suggested that low concentrations of FA could promote cell proliferation by accelerating cell division process or enhancing the Warburg effect to embody the Hormesis effect.

Physiological responses and metal uptake of Miscanthus under cadmium/arsenic stress.

The aim of this study is to explore the impact of cadmium (Cd) and arsenic (As) stress on physiological indexes and Cd/As uptake ability of Miscanthus, including Miscanthus sacchariflorus A0104, Miscanthus sinensis C0424 and C0640. Cd and As concentration showed significant hormesis effects on some physiological indexes, such as chlorophyll content, net photosynthetic rate, and MDA content. Compared with control group, Cd uptake can be most greatly enhanced by above fourfold with 150 mg/kg Cd treatment. As uptake of A0104 was increased by 3 ~ 33 folds with 200 mg/kg As treatment, C0424 was increased by 7-12 folds with 100 mg/kg As treatment, while C0640 was increased 1 ~ 6 folds with 250 mg/kg As treatment. The results also showed that C0640 was relatively better for the Cd remediation in the high Cd concentration (150 mg/kg) contaminated soil, while A0104 and C0424 were relatively better for the As remediation in the high As concentration (100 ~ 200 mg/kg) contaminated soil. Additionally, significantly (p < 0.05) close correlations were found among physiological indexes (except MDA content), while physiological indexes showed no significant relationship with the heavy metal contents in root, stem, and leaf.

Study on the interaction mechanism between cefradine and Chlamydomonas reinhardtii in water solutions under dark condition.

Our research investigated the hormesis effect of cefradine on the specific growth rates (µ) of single-celled algae (Chlamydomonas reinhardtii) from aqueous solutions. We found the specific growth rate of C. reinhardtii slightly increased with cefradine concentrations within the range 0.5-10 mg/L. Effects of algae density, initial solution pH, and temperature on the adsorption batch assays were investigated. The optimum conditions for cefradine adsorption occurred at a density of 5 × 106 algae cells/mL, a solution pH of 7.0, and a temperature of 25.0 °C. A Box-Behnken design was employed to evaluate correlations between influential factors and cefradine adsorption. The results showed a significant interaction between algae density and temperature. The maximum removal rate could reach 50.13% under the optimal conditions. Additionally, the adsorption mechanisms were explored through Langmuir and Freundlich isotherm equations, adsorption kinetics, and thermodynamics. The results suggested that the adsorption process was monolayer, spontaneous, and endothermic with an increase in randomness at the algae-solution interface, which followed a pseudo-second-order model. All the data indicated that the alga performed a better removal capacity in the antibiotic-containing wastewater treatment process. This study lays the groundwork for a better understanding of the interaction mechanism between cefradine and Chlamydomonas reinhardtii in water solutions under dark condition.

Sulfonated graphene-induced hormesis is mediated through oxidative stress in the roots of maize seedlings.

The present study investigated the impact of sulfonated graphene (SG) on the growth of maize seedlings at a concentration range of 0-500mgL-1. Stress-related parameters including reactive oxygen species (ROS), intracellular Ca2+, antioxidant enzyme activities, lipid peroxidation, membrane leakage, cell death and root morphology were examined to reveal the potential mechanisms. The results indicate that SG induced a hormesis effect on plant height, i.e., low-concentration (50mgL-1) stimulation and high-concentration (500mgL-1) inhibition. The hormesis effect of SG on plant height was directly correlated with ROS levels in roots. A low concentration (50mgL-1) of SG promoted ROS scavenging, alleviated oxidative stress, enhanced the soluble protein (SP) content, and decreased intracellular Ca2+ and cell death in the roots. At a higher concentration (500mgL-1), SG stimulated the generation of ROS in the roots, decreased SP content in the leaves, increased antioxidant enzyme activities, intracellular Ca2+, electrolyte leakage and cell death in the roots, and increased the malondialdehyde (MDA) content in both roots and leaves. Different changes were observed for root morphology at SG concentrations of 50 and 500mgL-1, and a larger amount of SG was deposited onto the root surface at a concentration of 500mgL-1 compared with 50mgL-1.

Lethal and sublethal effects of cyantraniliprole on Bactrocera dorsalis (Hendel) (Diptera: Tephritidae).

BACKGROUND: The oriental fruit fly, Bactrocera dorsalis (Hendel), is one of the most globally important insect pests. Studies were conducted with the novel anthranilic diamide insecticide cyantraniliprole to determine its lethal and sublethal effects on B. dorsalis. RESULTS: An ingestion toxicity bioassay showed that cyantraniliprole was active against B. dorsalis, and the 72 h feeding LC50 was 3.22 µg g(-1) in adult diet for a susceptible strain. Sublethal doses of cyantraniliprole (1.30 µg g(-1) adult diet) induced a hormesis effect on B. dorsalis. The mating competitiveness of B. dorsalis treated with cyantraniliprole at 3.27 µg g(-1) adult diet was significantly lower when compared with the controls. The lower dose (1.30 µg g(-1) adult diet) of cyantraniliprole improved the total mating times of both mating pairs in treated groups and also the mating competitiveness of the treated males when compared with the higher dose and controls. Cyantraniliprole-treated females of the mated pairs with the lower dose laid more eggs. On the fifth day, female receptivity in the treated group was significantly reduced when compared with the controls. CONCLUSION: These results indicate that cyantraniliprole is effective against B. dorsalis. The inhibition and stimulation effect of cyantraniliprole on the adult's mating performance at different concentrations was proved.