BPA promotes lung fibrosis in mice by regulating autophagy-dependent ferroptosis in alveolar epithelial cells.

BACKGROUND: Bisphenol A (BPA) is an industrial chemical that is commonly found in daily consumer products. BPA is reportedly associated with lung diseases. However, the impact of BPA on pulmonary fibrosis (PF) and its possible mechanisms of action both remain unclear. METHODS: A PF mouse model was induced by bleomycin (BLM). Mouse lung fibroblasts (MLG 2908) and mouse alveolar epithelial cells (MLE-12) were treated with BPA to establish a PF cell model. Tissue staining, CCK-8 assays, western blot experiments and relevant indicator kits were used to detect and evaluate the effect of BPA on PF. RESULTS: BPA dose-dependently promoted oxidative stress and induced ferroptosis, leading to PF. The ferroptosis inhibitor Fer-1 partly attenuated the effect of BPA. In addition, among the two main cell types associated with the progression of PF, MLE-12 cells are more sensitive to BPA than are MLG 2908 cells, and BPA induces ferroptosis in MLE-12 cells. Furthermore, BPA promoted autophagy-mediated ferroptosis by activating the AMPK/mTOR signaling pathway, thereby exacerbating the progression of PF. The autophagy inhibitor CQ1 partly attenuated the effect of BPA. CONCLUSION: BPA promotes the progression of PF by promoting autophagy-dependent ferroptosis in alveolar epithelial cells, which provides a new theoretical basis for understanding BPA-induced PF.

Role of miR-276-3p in the cyantraniliprole resistance mechanism of Bemisia tabaci via CYP6CX3 targeting.

The sweet potato whitefly, Bemisia tabaci, is an important insect pest that transmits over 200 different plant viruses and causes serious damage to the production of cotton and Solanaceae vegetables. Cyantraniliprole is the first diamide insecticide, showing toxicity against B. tabaci. However, B. tabaci has developed resistance to this insecticide by upregulating the expressions of cytochrome P450 genes such as CYP6CX3, while there is limited information on the regulatory mechanism mediated by miRNA. In the present study, ten miRNAs were predicted to target CYP6CX3, in which miR-276-3p showed an inverse expression pattern with CYP6CX3 in two cyantraniliprole resistant strains and under cyantraniliprole exposure. A luciferase assay demonstrated that miR-276-3p suppressed CYP6CX3 expression by pairing with residues 1445-1453. Overexpression or knockdown of miR-276-3p directly impacted B. tabaci resistance to cyantraniliprole. In addition, exposure to cyantraniliprole led to a significant reduction in the expressions of five genes (drosha, dicer1, dicer2, Ago1, and Ago2A) associated with miRNA biogenesis. Suppressing genes such as drosha, dicer1, and Ago2A reduced the expression of miR-276-3p, increased CYP6CX3 expression, and decreased B. tabaci resistance to cyantraniliprole. These results improve our understanding of the role of miRNAs in P450 regulation and cyantraniliprole resistance in B. tabaci.

The promoted degradation of biochar-adsorbed 2,4-dichlorophenol in the presence of Fe(III).

Organic pollutant degradation by biochar could be promoted by Fe because of the Fenton-like reaction. However, studies have also confirmed that reactive oxygen species (ROS) play only a limited role in organic pollutant degradation by biochar. Herein, we quantitatively identified 2,4-dichlorophenol (2,4-DCP) adsorption and degradation in Fe-biochar systems and obtained degradation (k1) and adsorption rate constants (k2) by two-compartment first-order kinetics modeling. The k1 was approximately 7-10 times lower than the corresponding k2 and the positive correlation between k1 and k2 illustrated that adsorption and degradation were kinetically associated. ROS quenching only slightly inhibited 2,4-DCP degradation. Chemicals with similar structures to ROS quenchers (without quenching ability) also inhibited 2,4-DCP degradation, probably because of the competition of the active degradation sites on biochars. Electrochemical analysis and pH-impact experiments further elucidated that 2,4-DCP underwent oxidation-dominated degradation in the adsorbed phase via direct electron transfer. Fe(III) obviously increased 2,4-DCP adsorption through cation bridging and enhanced electron density by Fe-O conjugations on the biochar surface, which facilitated subsequent degradation. This study emphasized the importance of degradation on the biochar solid phase and that a breakthrough of the mass transfer bottleneck of adsorption will greatly promote degradation.

The opposite influences of Cu and Cd cation bridges on sulfamethoxazole sorption on humic acids in wetting-drying cycles.

Wetting-drying cycles in the environment could change the inner- or outer-sphere complexation of heavy metal cations on natural organic matter (NOM) and then influence ternary interactions with organic contaminants - a rarely-discussed essential geochemical process. In this work, the sorption of sulfamethoxazole (SMX) on humic acids (HAs) mediated by cations (Cu2+ and Cd2+) was investigated. Considering that outer-sphere complexation could be transformed into inner-sphere complexation during vacuum freeze-drying, the role of inner- or outer-sphere complexation on SMX sorption was explored. The experimental sorption results and density functional theory (DFT) calculations suggested that Cu2+ and Cd2+ sorption on HAs was mainly outer- and inner-sphere complexation, respectively. Cd2+ consistently promoted SMX sorption on HAs, while Cu2+ promoted and inhibited SMX sorption before and after freeze-drying. The structure of HA-Cu complexes with inner-sphere complexation was more compact than those with outer-sphere complexation, which reduced the accessibility of sorption sites for SMX on HA-Cu and inhibited SMX sorption. However, the greater number of coordination sites of Cd2+ may provide more sorption sites and the structure of HA-Cd was looser. These findings provide a groundbreaking understanding of the sorption of organics on natural adsorbents in the presence of cations.

Sorption of organic contaminants by biochars with multiple porous structures: Experiments and molecular dynamics simulations mediated by three-dimensional models.

Interactions between organic pollutants and carbon-based particles are critical for understanding and predicting the fate of organic contaminants in the environment. However, traditional modeling concepts did not consider three-dimensional (3-D) structures of carbon-based materials. This prevents a deep understanding of the sequestration of organic pollutants. Therefore, this study revealed interactions between organics and biochars by combining experimental measurements and molecular dynamics simulations. Biochars displayed the best and worst sorption performances for naphthalene (NAP) and benzoic acid (BA), respectively, among the five adsorbates. The kinetic model fitting suggested that biochar pores played a vital role during sorption and led to the fast and slow sorption of organics on the biochar surface and in pores, respectively. Active sites on the biochar surface predominantly sorbed organics. Organics were only sorbed in pores when the surface's active sites were fully occupied. These results can guide the development of efficient organic pollution control strategies to protect human health and improve ecological security.

Association of C-reactive protein gene polymorphisms with the risk of ischemic stroke: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The heterogeneous, complex condition known as ischemic stroke (IS) is brought on by the interaction of a number of risk factors and genetic variables. The association between C-reactive protein (CRP) gene polymorphisms and IS has, however, been the subject of inconsistent findings. Therefore, we conducted a meta-analysis to comprehensively address possible associations of CRP genes with the risk of IS. METHODS: A comprehensive literature search for all the published articles was performed in electronic databases including PubMed, EMBASE, Cochrane Library, and Google Scholar from January 1, 1950 to June 30, 2022. Odds ratio (OR) with 95% Confidence interval (CIs) along with fixed/random effect models were used to calculate summary estimates. RESULTS: Twelve case-control studies totalling 3880 IS cases and 5233 controls were included for the association of CRP gene polymorphisms (rs1800947, rs1130864, rs3093059, rs2794521, and rs1205). Across all genotyping models, we discovered that rs1130864, rs3093059, rs2794521, and rs1205SNPs were not substantially related to IS risk. A trend for significant association for rs1800947 under dominant (OR = 1.19; 95% CI = 0.97 to 1.48), recessive (OR = 1.49; 95% CI = 0.71 to 3.14) and allelic model (OR = 1.21; 95% CI = 0.99 to 1.48) was observed. However, protective association for rs1130864 under dominant (OR = 0.80; 95% CI = 0.70 to 0.91) and rs3093059 under allelic model (OR = 0.18; 95% CI = 0.14 to 0.22) was found. CONCLUSION: Our thorough study revealed that the CRP gene variants rs1800947, rs1130864, rs3093059, rs2794521, and rs1205 could not be related to the risk of ischemic stroke. However, additional research must focus on the rs1800947 polymorphisms in a particular group.

Expression profile of CYP402C1 and its role in resistance to imidacloprid in the whitefly, Bemisia tabaci.

Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is a cosmopolitan insect pest causing serious damage to crop production. Cytochromes P450 (CYPs) of B. tabaci are widely known to be involved in the metabolic resistance to a variety of insecticides, continuously increasing the difficulty in controlling this pest. In this study, four P450 genes (CYP6CM1, CYP6CX1, CYP6CX3, and CYP402C1) in B. tabaci exhibited correlations with the resistance to imidacloprid. We have focused on trying to understand the function and metabolism capacity of CYP402C1. The expression profiles of CYP402C1 were examined by reverse transcription quantitative real-time PCR and fluorescence in situ hybridizations. Its role in resistance to imidacloprid was investigated by RNA interference, transgenic Drosophila melanogaster, and heterologous expression. The results showed that CYP402C1 was highly expressed in the active feeding stages of B. tabaci, such as nymphs and female adults. CYP402C1 was mainly expressed in midguts of nymphs and adults, especially in the filter chamber. Knockdown of CYP402C1 significantly decreased the resistance of B. tabaci to imidacloprid by 3.96-fold (50% lethal concentration: 186.46 versus 47.08 mg/L). Overexpression of CYP402C1 in a transgenic D. melanogaster line (Gal4 > UAS-CYP402C1) significantly increased the resistance to imidacloprid from 12.68- to 14.92-fold (129.01 and 151.80 mg/L versus 1925.14 mg/L). The heterologous expression of CYP402C1 showed a metabolism ability of imidacloprid (imidacloprid decreased by 12.51% within 2 h). This study provides new insights for CYP402C1 function in B. tabaci and will help develop new strategies in B. tabaci control and its insecticide resistance.

Biochar modification to enhance arsenic removal from water: a review.

Arsenic (As) contamination is a major threat to drinking water quality throughout the world, and the development of appropriate remediation methods is critical. Adsorption is considered the most effective method for remediation of As-contaminated water. Biochar is a promising adsorbent and widely discussed for As removal due to its potential low cost and environmental friendliness. However, pristine biochar generally exhibited relatively low adsorption capacity for As mainly due to the electrostatic repulsion between the negatively charged biochar and As. Biochar modification, especially metal modification, was developed to boost the adsorption capacity for As. A systematic analysis of As removal as affected by biochar properties and modification will be of great help for As removal. This paper presents a comprehensive review on As removal by biochars from different feedstock, preparation procedures, and modification methods, with a major focus on the possible mechanisms of interaction between As and biochar. Biochar derived from sewage sludge exhibited relatively high adsorption capacity for As. Considering energy conservation, biochars prepared at 401-500 °C were more favorable in adsorbing As. Fe-modified biochar was the most popular modified biochar for As remediation due to its low cost and high efficiency. In addition, the limitations of the current studies and future perspectives are presented. The aim of this review is to provide guidance for the preparation of low-cost, environmentally friendly, and high efficiency biochar for the remediation of As-contaminated water.

Cytochrome P450 Gene, CYP6CX3, Is Involved in the Resistance to Cyantraniliprole in Bemisia tabaci.

Bemisia tabaci is an important agricultural sucking pest, and it develops serious resistance to various insecticides. Although cytochrome P450 was involved in the resistance to cyantraniliprole, limited studies have been conducted on B. tabaci. In the present study, piperonyl butoxide significantly increased the toxicity of cyantraniliprole. P450 activities in two resistant populations were 1.97- and 2.17-fold higher than that in the susceptible population. Among 79 P450 genes, CYP6CX3 expressions in two resistant populations were 3.08- and 3.67-fold higher than that in the susceptible population. When CYP6CX3 was knocked down, the toxicity of cyantraniliprole increased significantly. The LC50 value of cyantraniliprole to the Drosophila melanogaster line overexpressing B. tabaci CYP6CX3 increased 7.34-fold. The content of cyantraniliprole was decreased by 25.74 ± 4.27% after mixing with CYP6CX3 and CPR for 2 h. These results suggested that the overexpression of CYP6CX3 was likely involved in the resistance to cyantraniliprole in B. tabaci.

Molecular clusters played an important role in the adsorption of polycyclic aromatic hydrocarbons (PAHs) on carbonaceous materials.

Polycyclic aromatic hydrocarbons (PAHs) are one of the most frequently detected hydrophobic organic contaminants (HOCs) in the environment. They may form clusters because of the strong hydrophobic and π-π electron-donor-acceptor (EDA) interactions among PAHs molecules. However, previous experimental studies and theoretical simulations generally ignored the impact of molecular clusters on the adsorption, which may result in the misunderstanding of the environmental fate and risk. In this work, naphthalene (NAP), phenanthrene (PHE), and pyrene (PYR) were selected to investigate intermolecular interaction as well as the consequent impact on their adsorption on graphene. The density field of C atoms in equilibrium configurations of self-interacted PAHs suggested that the formation of PAHs molecular clusters was a spontaneous process, and was favored in solvents with stronger polarity and for PAHs with more benzene rings. It should be noted that the molecular dynamics simulations with the initial state of molecular clusters matched better with the published experimental results compared with those of individual PAHs. The formed compact PAHs clusters in polar solvents increased the apparent PAHs adsorption, because of their higher hydrophobic and π-π EDA interactions. This study emphasized that the self-interaction of PAHs should be carefully considered in both experimental and theoretical simulation studies.

NLRP3 inflammasome contributes to endotoxin-induced coagulation.

INTRODUCTION: Excessive activation of the coagulation cascades leads to life-threatening disseminated intravascular coagulation (DIC) in sepsis. Two recent studies by our group and others have both demonstrated the noncanonical inflammasome is pivotal for the endotoxin or gram-negative bacterial-induced coagulation. Based on this, we further evaluated the function of the NLRP3 inflammasome, the most studied inflammasome, in endotoxin-induced coagulation. MATERIALS AND METHODS: We established an endotoxin-induced coagulation model by intraperitoneal injection of sublethal doses of LPS in mice. Mice were sacrificed 8 h after injection and blood was collected for thrombin-antithrombin (TAT), plasminogen activator inhibitor-1 (PAI-1), prothrombin time (PT), D-dimer, IL-1ß and tissue factor (TF) measurements by commercial ELISA. Lungs and livers were examined via HE staining images to determine injury scores and immunohistochemistry for TF expression and fibrin deposits. The role of NLRP3 activation was evaluated in wild-type (WT), Nlrp3-/-, Asc-/- (apoptosis-associated speck-like protein containing a CARD), Caspase-11-/- mice and 30 min after treatment with MCC950, a potent inhibitor of NLRP3. Western blotting and Q-PCR were performed to assess TF expression in the lungs and livers. To uncover the different effects of NLRP3 and Caspase-11, we also compared the time-dependent IL-1ß release in LPS-treated Nlrp3-/- and Caspase-11-/- mice. Correlation analysis of TAT, PAI-1 were estimated the relationship of coagulation and release of IL-1ß, as well as IL-1ß and TF. RESULTS: Inhibition of NLRP3 by MCC950 as well as NLRP3 or ASC deficiency decreased TAT, PAI-1, PT, D-dimer, and TF levels in blood and impaired the thrombus formation and fibrin deposition, as well as declined expression of TF in the liver and lung in endotoxin-induced coagulation but not caspase-11 deficiency. Impressively, IL-1ß release is increased in LPS-treated Caspase-11-/- mice, but not in Nlrp3-/- mice. Moreover, the correlation analysis is indicated that downstream of the NLRP3 inflammasome, IL-1ß expression, is positively correlated with TAT, PAI-1 and TF in blood circulation. CONCLUSIONS: The NLRP3 inflammasome contributes to endotoxin-induced coagulation by promoting TF expression at least in part through the induction of IL-1ß release. These findings broadened our understanding of the mechanism of coagulation and implicated a possible therapeutic strategy for preventing coagulation in sepsis.

Nanomedicines, an emerging therapeutic regimen for treatment of ischemic cerebral stroke: A review.

Owing to its intricate pathophysiology, cerebral stroke is a serious medical condition caused by interruption or obstruction of blood supply (blockage of vasculature) to the brain tissues which results in diminished supply of essential nutrients and oxygen (hypoxia) and ultimate necrosis of neuronal tissues. A prompt risks assessment and immediate rational therapeutic plan with proficient neuroprotection play critically important role in the effective management of this neuronal emergency. Various conventional medications are being used for treatment of acute ischemic cerebral stroke but fibrinolytic agents, alone or in combination with other agents are considered the mainstay. These clot-busting agents effectively restore blood supply (reperfusion) to ischemic regions of the brain; however, their clinical significance is hampered due to various factors such as short plasma half-life, limited distribution to brain tissues due to the presence of highly efficient physiological barrier, blood brain barrier (BBB), and lacking of target-specific delivery to the ischemic brain regions. To alleviate these issues, various types of nanomedicines such as polymeric nanoparticles (NPs), liposomes, nanoemulsion, micelles and dendrimers have been designed and evaluated. The implication of these newer therapies (nanomedicines) have revolutionized the therapeutic outcomes by improving the plasma half-life, permeation across BBB, efficient distribution to ischemic cerebral tissues and neuroprotection. Furthermore, the adaptation of some diverse techniques including PEGylation, tethering of targeting ligands on the surfaces of nanomedicines, and pH responsive features have also been pondered. The implication of these emerging adaptations have shown remarkable potential in maximizing the targeting efficiency of drugs to ischemic brain tissues, simultaneous delivery of drugs and imaging agents (for early prognosis as well as monitoring of therapy), and therapeutic outcomes such as long-term neuroprotection.

Notoginsenoside R2 reduces Aß25-35-induced neuronal apoptosis and inflammation via miR-27a/SOX8/ß-catenin axis.

Background: Alzheimer's disease (AD) has affected numerous elderly individuals worldwide. Panax notoginseng has been shown to ameliorate AD symptoms, and notoginsenoside R2 is a key saponin identified in this plant. Purpose: In the current study, we aimed to explore whether notoginsenoside R2 could improve the prognosis of AD. Methods: Herein, primary rat cortical neurons were isolated and they were treated with amyloid beta-peptide (Aß) 25-35 oligomers. Cellular apoptosis was examined via flow cytometry and Western blotting. miR-27a and SOX8 mRNA expression levels were quantified by quantitative reverse transcription-polymerase chain reaction. Furthermore, the interaction between miR-27a and SOX8 was investigated by utilizing a dual-luciferase reporter assay. Finally, an AD mouse model was established to validate the in vitro findings. Results: Notoginsenoside R2 alleviated Aß25-35-triggered neuronal apoptosis and inflammation. During this process, miR-27a expression was decreased by notoginsenoside R2, and miR-27a negatively modulated SOX8 expression. Furthermore, activation of SOX8 upregulated ß-catenin expression, thus suppressing apoptosis and neuroinflammation. Conclusions: Our animal experiments revealed that notoginsenoside R2 enhanced the cognitive function of AD mice and inhibited neuronal apoptosis. Notoginsenoside R2 ameliorated AD symptoms by reducing neuronal apoptosis and inflammation, thus suggesting a novel direction for AD pharmacotherapy.

Characterization of the ryanodine receptor gene in Encarsia formosa (Gahan) and its expression profile in response to diamide insecticides.

Ryanodine receptors (RyRs) are the targets of diamide insecticides, which have been identified and characterized in a dozen insect pests of Lepidoptera, Hemiptera, Diptera and Coleoptera, but limited attention has been paid to the RyR in parasitoid natural enemies. Without this knowledge, it will hinder our effective and efficient application using both parasitoid natural enemies and diamide insecticides simultaneously in the integrated pest management (IPM). In this study, the full-length cDNA of RyR was cloned from Encarsia formosa (EfRyR), a parasitic wasp used worldwide for the biological control of whitefly. Its expression profile was examined in various tissues of E. formosa adults. The toxicities of four diamide insecticides to E. formosa were measured, and then the expression profile of EfRyR after 12 h and 24 h exposure to the LC50 dosages of diamide insecticides was investigated. The results showed that the full-length cDNA of EfRyR was 16, 778 bp including a 15, 345 bp open reading frame, and two alternative splice (AS) sites. Comparing to its expression in the abdomen, EfRyR was highly expressed in the head (11.9-fold) and the thorax (3.7-fold). The toxicities of four dimide insecticides against E. formosa from low to high were chlorantraniliprole (LC50 = 367.84 mg L-1), cyantraniliprole (221.72 mg L-1), cyclaniliprole (51.77 mg L-1), and tetrachlorantraniliprole (8.35 mg L-1). The expressions of EfRyR and its variants with AS were significantly increased after E. formosa adults were exposed to different diamide insecticides. This study improves our understanding of the RyR in parasitoid wasps and provides useful information on IPM by using E. formosa.

Dual roles of biochar redox property in mediating 2,4-dichlorophenol degradation in the presence of Fe3+ and persulfate.

Recent studies suggested that biochars could mediate the degradation of organic contaminants. The role of biochars in mediating organic contaminant degradation could be amplified in a Fenton-like reaction, and comparing biochars with varied properties may provide insightful information to understand the reaction mechanisms. In this study, biochar was applied in a Fenton-like reaction system with Fe3+ and persulfate (PS) to degrade 2,4-dichlorophenel (2,4-DCP). Biochars with different intensities of persistent free radicals (PFRs), oxygen-containing functional groups (OFGs), and redox properties were investigated regarding their roles in 2,4-DCP removal. Compared to biochar system, PS addition increased 2,4-DCP degradation and Fe3+ addition increased its sorption. The combination of PS and Fe3+ promoted 2,4-DCP degradation over 2 times higher. Various reactive oxygen species (ROS), including SO4•-, HO•, and O2•-, were involved in 2,4-DCP degradation, contributing to around 50% of the overall 2,4-DCP degradation. The direct electron transfer between biochar particles and 2,4-DCP contributed to the rest of 2,4-DCP degradation. A significant positive correlation was observed between 2,4-DCP degradation and electron donating capacity (EDC) or Fe2+. We thus concluded that EDC-involved structures in biochars could either directly donate electron to 2,4-DCP, or reduce Fe3+ to Fe2+, which activated PS to generate ROS. This dual roles of biochar should be well considered in biochar application and production. This study provided a useful theoretical basis for manipulating biochar redox properties to enhance their application potential in pollution control.

Ferritin reduction is essential for cerebral ischemia-induced hippocampal neuronal death through p53/SLC7A11-mediated ferroptosis.

Cerebral ischemia is the most common cause of hippocampal neuronal death and the most prevalent cause of stroke with high mortality rate. Ferroptosis has been suggested to affect the role of hippocampal neurons. This study explores the influence of lentivirus infection-induced ferritin overexpression in hippocampal neuronal injury and death through simulations in August Copenhagen Irish rat models. Twenty-four-hour cerebral ischemia-reperfusion injury was induced in the rats after 90-min middle cerebral artery occlusion (MCAO). Ferritin overexpression was induced through lentivirus infection. The Morris Water Maze (MWM) test and tau hyperphosphorylation test were performed on hippocampal neurons to establish a MCAO model. The effect of ferritin overexpression on hippocampal neuronal death was evaluated using hematoxylin-eosin staining and annexin V/propidium iodide flow cytometry. The MWM test revealed that MCAO modeling decreased the cognitive and locomotor capacity of the rats, whereas ferritin overexpression partially reversed the effect of MCAO. In addition, the hyperphosphorylation of tau caused by MCAO was reduced by ferritin. Pathogenic changes, impaired viability, increased apoptosis, and elevated caspase-9 cleavage in hippocampal neurons were clearly recovered by ferritin. Moreover, robust reactive oxygen species production and glutathione consumption, which was induced by MCAO modeling, were ameliorated by ferritin. Furthermore, two key modulators of ferroptosis, p53 and SLC7A11, were demonstrated to be upregulated by MCAO modeling and downregulated by ferritin. Ferritin reduction is essential for cerebral ischemia-induced hippocampal neuronal ferroptosis mediated via p53 and SLC7A11.