The mode of action of different organochlorine pesticides families in mammalians.

Organochlorine pesticides (OCPs) show differences in their chemical structure, mechanism of toxicity, and target organisms. However, OCPs also have some common characteristics such as high persistence in the environment, bioaccumulation, and toxicity which lead to health issues. Nowadays, the toxicity of OCPs is well known, but we still do not know all the specific molecular mechanisms leading to their toxicity in mammalians. Therefore, this review aims to collect data about the mode of action of various classes of OCPs, highlighting their differences and common behavioural reactions in the human and animal body. To discuss the OCPs molecular pathways and fate in different systems of the body, three organochlorine insecticides were selected (Dichlorodiphenyltrichloroethane, Hexachlorocyclohexane and Chlordecone), regarding to their widespread use, with consequent effects on the ecosystem and human health. Their common biological responses at the molecular scale and their different interactions in human and animal bodies were highlighted and presented.

Assessment of Malondialdehyde and Organochlorine Pesticides in Aplastic Anemia Severity Groups: Insights Into Oxidative Stress and Exposure.

Background There is little evidence that pesticide exposure is the primary cause of acquired aplastic anemia (AAA), even though the prevalence of aplastic anemia (AA) is substantially higher in underdeveloped countries than in affluent countries. AA caused by pesticides has not yet been fully understood. This study aimed to examine the potential link between plasma levels of malondialdehyde (MDA) and organochlorine pesticides (OCPs) as risk factors for developing AAA in the North Indian population. Methods This case-control study was conducted at a tertiary care hospital in North India. A total of 99 participants were chosen for the study, of whom 45 were cases of AA. These cases attended the Clinical Hematology department over a period of 1.5 years (May 2018 to November 2019). Forty-five controls were age and sex-matched, apparently healthy subjects. Written informed consent was obtained from each subject before performing the study. Exclusion criteria included patients unwilling to give consent, those using medication to treat AA, those genetically predisposed to AA, those with characteristics including granuloma and dysplasia of bone marrow, any other systemic illness, and subjects with a history of smoking, drinking, or using tobacco in any form. Gas chromatography-tandem mass spectrometry (GC-MS/MS) was used to evaluate the plasma levels of organochlorines. The estimation of plasma MDA, i.e., the lipid peroxide content, was measured. Results The severity of AA is significantly associated with plasma levels of α-Hexachlorocyclohexane (p = 0.040), Heptachlor (p = 0.006), Aldrin (p < 0.001), p,p'-Dichlorodiphenyldichloroethane (p = 0.004), Endosulfan sulfate (p = 0.010), and Methoxychlor (p = 0.001). There was a statistically non-significant difference in MDA levels between cases and controls (p = 0.145); however, a statistically significant linear increase in MDA levels (p < 0.001) was observed according to the severity of AA. Conclusion Our study suggests that oxidative stress may be linked to the severity of AA. Pesticide exposure (plasma organochlorine levels) could act as a stressor, potentially initiating an alarmin response of oxidative stress in the form of lipid peroxidation (MDA) from damaged tissue, which could then lead to suppression of hematopoiesis and be a possible factor in the development of AA.

Transgenic Arabidopsis thaliana plants expressing bacterial γ-hexachlorocyclohexane dehydrochlorinase LinA.

BACKGROUND: γ-Hexachlorocyclohexane (γ-HCH), an organochlorine insecticide of anthropogenic origin, is a persistent organic pollutant (POP) that causes environmental pollution concerns worldwide. Although many γ-HCH-degrading bacterial strains are available, inoculating them directly into γ-HCH-contaminated soil is ineffective because of the low survival rate of the exogenous bacteria. Another strategy for the bioremediation of γ-HCH involves the use of transgenic plants expressing bacterial enzyme for γ-HCH degradation through phytoremediation. RESULTS: We generated transgenic Arabidopsis thaliana expressing γ-HCH dehydrochlroninase LinA from bacterium Sphingobium japonicum strain UT26. Among the transgenic Arabidopsis T2 lines, we obtained one line (A5) that expressed and accumulated LinA well. The A5-derived T3 plants showed higher tolerance to γ-HCH than the non-transformant control plants, indicating that γ-HCH is toxic for Arabidopsis thaliana and that this effect is relieved by LinA expression. The crude extract of the A5 plants showed γ-HCH degradation activity, and metabolites of γ-HCH produced by the LinA reaction were detected in the assay solution, indicating that the A5 plants accumulated the active LinA protein. In some A5 lines, the whole plant absorbed and degraded more than 99% of γ-HCH (10 ppm) in the liquid medium within 36 h. CONCLUSION: The transgenic Arabidopsis expressing active LinA absorbed and degraded γ-HCH in the liquid medium, indicating the high potential of LinA-expressing transgenic plants for the phytoremediation of environmental γ-HCH. This study marks a crucial step toward the practical use of transgenic plants for the phytoremediation of POPs.

2D model of groundwater flow and total dissolved HCH transport through the Gállego alluvial aquifer downstream the Sardas landfill (Huesca, Spain).

The organic pollutants disposed at the Sardas landfill in Sabiñánigo (Huesca, northeastern Spain) by the INQUINOSA lindane factory have reached the Gállego alluvial aquifer and could affect the Sabiñánigo reservoir. The daily oscillations of the reservoir water level produce a tidal effect on the piezometric heads of the aquifer. These oscillations are transmitted in a damped way with a time lag, thus attesting that the silting sediments of the reservoir and the natural silts of the Gállego alluvial are interposed between the reservoir water and the layer of sands and gravels. A 2D finite element groundwater flow and total dissolved hexachlorocyclohexane (HCH) transport model through the Gállego alluvial aquifer is presented here. The flow model was constructed to: (1) Quantify the tidal effect, produced by the daily fluctuations of the reservoir water level on the aquifer; (2) Estimate the hydrodynamic parameters of the layer of sands and gravels; and 3) Estimate the vertical hydraulic conductivity of the silting sediments and silts; and (4) Quantify aquifer/reservoir interactions. The flow model reproduces the dynamics of the tidal effect and attests that groundwater velocity and flow direction changes daily in response to the oscillations of the reservoir level. Model results reproduce the measured well hydrographs and the Darcy velocity derived from tracer tests and confirm the validity of the conceptual model. The transport model of total dissolved HCH simulates the time evolution of the contaminant plume. The computed concentrations of total dissolved HCH and the contaminant mass outflux are very sensitive to changes in the source terms and the distribution coefficient, Kd of HCH. The best fit to the measured HCH plumes in September 2010 and December 2020 is obtained with a Kd ranging from 1 to 3 L/kg. The computed flux of dissolved HCH leaving the Sardas site in 2020 towards the Sabiñánigo reservoir ranges from 0.6 kg/year for Kd = 3 L/kg to 3.1 kg/year for Kd = 1 L/kg. The findings of this study will be most useful for planning and designing remedial and containment actions at the Sardas site and other similar lindane-affected sites.

Grain transportation and consumption reshapes the α-HCH exposure picture of China.

Socio-economic activities like food trade can increase the uncertainty of human risk of persistent organic pollutants (POPs). We compared the change in model predicted α-hexachlorocyclohexane (α-HCH) cancer risk (CR) with and without grain trade in mainland China. In scenario without grain logistics, α-HCH moved fast away from southern and southeastern China via northward atmospheric transport. However, the grain logistics from northeastern China delivers the α-HCH previously accumulated in northeastern sink back to densely populated areas in recent years, which enhance CR by >50 % in the southern seaboard of China. The northward movement of grain production center and recent grain deficiency in southern provinces induced by dietary pattern changes is identified as the major driving factors of the reversed transport of α-HCH. The finding highlights the potential of socio-economic activities that can otherwise offset the risk reduction effect of the geochemical cycle of POPs.

Application of hospital-community-home linkage management model in patients with type 2 diabetic nephropathy.

OBJECTIVE: To explore the effect of the hospital-community-home (HCH) linkage management mode in patients with type 2 diabetic nephropathy (DN). METHOD: A total of 80 patients with type 2 DN hospitalised in the Department of Nephrology of our hospital between July 2021 and June 2022 were recruited and subsequently divided into the observation group and the control group using the random number table method, with 40 patients in each group. The control group received routine health education and discharge guidance. The HCH linkage management model was implemented for the observation group based on routine care. The improvements in compliance behaviour, biochemical parameters of renal function, blood glucose level and self-management ability were compared before the intervention and at 3 and 6 months after the intervention. RESULTS: After the intervention, the scores for compliance behaviour of the observation group were better than those of the control group, with a statistically significant difference (P < 0.05). The biochemical indicators of renal function and blood glucose level were significantly lower in the observation group compared with in the control group, with a statistically significant difference (P < 0.05). After the intervention, the observation group showed a great improvement in self-management ability and cognition of the disease, with significant differences (P < 0.05). CONCLUSION: The HCH linkage management mode can improve the compliance behaviour of patients with type 2 DN, effectively improve the renal function and blood sugar level of patients, enhance the self-management ability and cognition of the disease and delay the development of the disease.

FPR1: A critical gatekeeper of the heart and brain.

G protein-coupled receptors (GPCRs) are currently the most widely focused drug targets in the clinic, exerting their biological functions by binding to chemicals and activating a series of intracellular signaling pathways. Formyl-peptide receptor 1 (FPR1) has a typical seven-transmembrane structure of GPCRs and can be stimulated by a large number of endogenous or exogenous ligands with different chemical properties, the first of which was identified as formyl-methionine-leucyl-phenylalanine (fMLF). Through receptor-ligand interactions, FPR1 is involved in inflammatory response, immune cell recruitment, and cellular signaling regulation in key cell types, including neutrophils, neural stem cells (NSCs), and microglia. This review outlines the critical roles of FPR1 in a variety of heart and brain diseases, including myocardial infarction (MI), ischemia/reperfusion (I/R) injury, neurodegenerative diseases, and neurological tumors, with particular emphasis on the milestones of FPR1 agonists and antagonists. Therefore, an in-depth study of FPR1 contributes to the research of innovative biomarkers, therapeutic targets for heart and brain diseases, and clinical applications.

Back on top: Resuspended by dredging and other environmental disturbances, organochlorine compounds may affect the health of a dolphin population in a tropical estuary, Sepetiba Bay.

Organochlorine compounds (OCs) are persistent organic pollutants linked to damaging the immune and endocrine systems, leading to a greater susceptibility to infectious diseases at high concentrations. Sepetiba Bay, in the Southeastern Brazilian coast, historically presents anthropogenic activities and environmental contamination that could negatively impact resident populations. In this context, this study aimed to investigate the temporal trends in the accumulation of organochlorine compounds over a 12-year database in the Guiana dolphins' (Sotalia guianensis) resident population from Sepetiba Bay, including individuals collected before, during, and after an unusual mortality event triggered by morbillivirus (n = 85). The influence of biological parameters was also evaluated. The OCs concentrations in the blubber ranged from 0.98 to 739 µg/g of ΣPCB; 0.08-130 µg/g of ΣDDT; <0.002-4.56 µg/g of mirex; <0.002-1.84 µg/g of ΣHCH and <0.001-0.16 µg/g of HCB in lipid weight. Increased temporal trends were found for OCs in Guiana dolphins coinciding with periods of large events of dredging in the region. In this way, our findings suggest that the constant high OCs concentrations throughout the years in this Guiana dolphin population are a result of the constant environmental disturbance in the area, such as dredging. These elevated OCs levels, e.g., ΣPCB concentrations found above the known thresholds, may impair the response of the immune system during outbreak periods, which could lead the population to a progressive decline.

Assessment of chlorinated pesticide exposure to white-rumped vulture Gyps bengalensis in India.

Populations of the critically endangered white-rumped vulture (WRV) Gyps bengalensis have declined drastically due to the use of diclofenac for veterinary purposes in Indian subcontinent. Thirty-two dead WRVs collected from three states, namely Gujarat, Assam and Tamil Nadu in India between 2011 and 2014 were investigated to understand the role of diclofenac in the death, and the results were published. Furthermore, since organochlorine pesticides have been linked to long-term impact on populations in many species of birds across the globe, available tissues of 21 WRVs were tested also for six organochlorine pesticides (DDT, HCH, endosulfan, heptachlor, dieldrin and dicofol) and chlorpyrifos. All vultures were found to have had one or more detectable levels of pesticides in their tissues except one. Similarly, all the pesticides included in the study were detected in at least one of the vultures analysed. DDT (95.2%) was the most frequently detected pesticide followed by HCH (90.5%), and DDT (73.6%) contributed the most to the total pesticide load. Total pesticide load ranged between below detection limit (BDL) and 8753.4 ng/g. High levels of total pesticide load recorded in gut contents showed recent exposure to these legacy pesticides even long after their ban. However, it is perceived that studied pesticides' exposure to birds and their presence in the environment is in decreasing trend in India. Although, varying levels of pesticides were detected, all of which were below the levels reported to be toxic, and also reported earlier in the same species in India. Recorded levels may not create a problem to vultures unlike diclofenac; nevertheless, as continued exposure to the pesticides studied may lead to sub lethal effects in birds, it is prudent to monitor these pesticides along with new generation pesticides and NSAIDs in the critically endangered white-rumped vulture in India, towards its conservation.

Perinatal exposure to potential endocrine disrupting chemicals and autism spectrum disorder: From Norwegian birth cohort to zebrafish studies.

BACKGROUND: The etiology of autism spectrum disorder (ASD) is multifactorial, involving genetic and environmental contributors such as endocrine-disrupting chemicals (EDCs). OBJECTIVE: To evaluate the association between perinatal exposure to 27 potential EDCs and ASD among Norwegian children, and to further examine the neurodevelopmental toxicity of associated chemicals using zebrafish embryos and larvae. METHOD: 1,199 mothers enrolled in the prospective birth-cohort (HUMIS, 2002-2009) study. Breastmilk levels of 27 chemicals were measured: polychlorinated biphenyls, organochlorine pesticides, polybrominated diphenyl ethers, and perfluoroalkyl substances as a proxy for perinatal exposure. We employed multivariable logistic regression to determine association, utilized elastic net logistic regression as variable selection method, and conducted an in vivo study with zebrafish larvae to confirm the neurodevelopmental effect. RESULTS: A total of 20 children had specialist confirmed diagnosis of autism among 1,199 mother-child pairs in this study. ß-Hexachlorocyclohexane (ß-HCH) was the only chemical associated with ASD, after adjusting for 26 other chemicals. Mothers with the highest levels of ß-HCH in their milk had a significant increased risk of having a child with ASD (OR = 1.82, 95 % CI: 1.20, 2.77 for an interquartile range increase in ln-transformed ß-HCH concentration). The median concentration of ß-HCH in breast milk was 4.37 ng/g lipid (interquartile range: 2.92-6.47), and the estimated daily intake (EDI) for Norwegian children through breastfeeding was 0.03 µg/kg of body weight. The neurodevelopmental and social behavioral effects of ß-HCH were established in zebrafish embryos and larvae across various concentrations, with further analysis suggesting that perturbation of dopaminergic neuron development may underlie the neurotoxicity associated with ß-HCH. CONCLUSIONS: Prenatal exposure to ß-HCH was associated with an increased risk of specialist-confirmed diagnoses of ASD among Norwegian children, and the EDI surpasses the established threshold. Zebrafish experiments confirm ß-HCH neurotoxicity, suggesting dopaminergic neuron disruption as a potential underlying mechanism.

Plasma Levels of Organochlorine Pesticides and Tumor Necrosis Factor-Alpha: A Potential Risk Factor for Developing Acquired Aplastic Anemia in the North Indian Population.

Background Pesticide exposure might have a contributory role in the development of acquired aplastic anemia (AA). However, the precise mechanisms of pesticide-induced AA remain unknown. In this case-control study, we conducted a comparative analysis of plasma levels of organochlorine pesticides (OCP) and tumor necrosis factor-alpha (TNF-alpha) between Indian patients diagnosed with AA and an age- and sex-matched control group. Methods This is an observational case-control study conducted at a tertiary care hospital in North India. In this study, 90 subjects were included, out of which 45 were diagnosed with AA according to the criteria of the International Agranulocytosis and Aplastic Anemia Study. Cases were compared with 45 controls. A trained interviewer gave all study subjects a questionnaire to collect data regarding demographic details, exposure to pesticides, and clinical history. Physical examination and routine laboratory investigations of each subject were performed. Both cases and controls were tested for their plasma levels of organochlorines as per established protocol by gas chromatography-mass spectrometry. TNF-alpha level was measured by enzyme-linked immunosorbent assay in each subject. Results There was a significant increase in plasma levels of delta hexachlorocyclohexane (delta HCH) (p = 0.02) and heptachlor (p = 0.00) in patients with AA as compared to controls. We observed nonsignificant trends towards higher levels of beta HCH (p = 0.643), aldrin (p = 0.399), and p,p'-Dichlorodiphenyltrichloroethane (p,p'-DDT) (p = 0.453) in patients with AA when compared to the controls. There were significantly higher TNF-alpha levels (p = 0.024) in cases as compared to the controls. Conclusion Our study concludes that patients with AA exhibited higher levels of delta-HCH, heptachlor, and TNF-alpha in comparison to the control group. There is a significant positive correlation of TNF alpha with OCPs (alpha HCH, lindane, delta HCH, heptachlor, aldrin, p,p'- DDD, and methoxychlor pesticides). These organochlorines may have accumulated in the fatty tissue of bone marrow because of their lipophilic nature. This suggests that they might have served as a neoantigen to trigger an increase in TNF-alpha production, which may have led to disrupted bone marrow function through cell-mediated immunity, leading to AA.

Degradation of DDT by γ-hexachlorocyclohexane dehydrochlorinase LinA.

1,1,1-Trichloro-2,2-bis(4-chlorophenyl)-ethane (DDT) is the first synthetic insecticide and one of the most widely used pesticides. The use of DDT has been banned, but it remains one of the most notorious environmental pollutants around the world. In this study, we found that γ-hexachlorocyclohexane (γ-HCH) dehydrochlorinase LinA from a γ-HCH-degrading bacterium, Sphingobium japonicum UT26, converts DDT to 1,1-dichloro-2,2-bis(4-chlorophenyl)-ethylene (DDE). Because of the weak DDT degradation activity of LinA, we could not detect such activity in UT26 cells expressing LinA constitutively. However, the linA-deletion mutant of UT26 harboring a plasmid for the expression of LinA, in which LinA was expressed at a higher level than UT26, showed the DDT degradation activity. This outcome highlights the potential for constructing DDT-degrading sphingomonad cells through elevated LinA expression.

Spatial redistribution and enantiomeric signatures of hexachlorocyclohexanes in Chinese forest soils: Implications to environmental behavior and influencing factors.

Hexachlorocyclohexanes (HCHs) are a group of highly persistent pesticides. The concentrations of HCHs and the enantiomeric fractions of α-HCH in the O- and A-horizons from 30 mountains across China were analyzed in this study. The concentrations of total HCHs ranged from 0.061 to 46.9 ng/g (mean 2.12 ng/g) and 0.046 to 16.1 ng/g (mean 0.792 ng/g) in the O- and A-horizons, respectively. The HCH residues were mainly derived from the historical applications of technical HCH and lindane. Higher concentrations of HCHs were typically found in northern China, and no significant correlations were found between historical technical HCH usage and HCH isomer concentrations in either the O- or A-horizons (p > 0.05). Conversely, the concentrations of HCH isomers were significantly correlated with the environmental parameters (temperature and precipitation), thus indicating a typical secondary distribution pattern. Some HCH isomers tended to be transported northward under the long-term effect of monsoon. Chiral α-HCH was non-racemic in soils and showed preferential degradation of (-) α-HCH in both the O- and A-horizons. The transformation from γ-HCH to α-HCH might alter the enantiomeric signatures of α-HCH in soils. Moreover, the deviation from racemic of α-HCH was positively correlated with the C/N ratio in the A-horizon (p < 0.01), thus suggesting that the C/N ratio could alter the microbial activity and significantly affect the enantioselective degradation extent of α-HCH in soils.

Improving Gastrointestinal Cancer Care by Enhanced Recovery Protocol Implementation.

Background: Enhanced recovery protocols (ERPs) have become the standard of care for patients undergoing elective small bowel surgeries but have not yet been adequately studied in community hospitals. In this study, a multidisciplinary ERP was developed and implemented at a community hospital to include minimal anesthesia, early ambulation and enteral alimentation, and multimodal analgesia. The aim of this study was to determine the effects of the ERP on postoperative length of stay (LOS), readmission (RA) rates following bowel surgery, and postoperative outcomes. Methods: The study design was a retrospective review of patients undergoing major bowel resection at Holy Cross Hospital (HCH) from January 1, 2017 to December 31, 2017. Patient charts for diagnostic-related group (DRG) 329, 330, and 331 were retrospectively reviewed at HCH in 2017 to compare outcomes in ERP versus non-ERP cases. The Medicare claims database (CMS) was also retrospectively reviewed to compare HCH data to the national average LOS and RA for the same DRG codes. Mean values for LOS and RA were statistically compared to determine significant differences between ERP versus non-ERP patients at HCH and national CMS data versus HCH patients. Results: LOS was analyzed for each DRG at HCH. At HCH, for DRG 329, the mean LOS for non-ERP was 13.0833 days (n = 12) versus 3.375 days (n = 8) (P ≤ 0.001) for ERP. For DRG 330, the mean LOS for non-ERP was 10.861 days (n = 36) versus 4.583 days (n = 24) (P ≤ 0.001) for ERP. For DRG 331, the mean LOS for non-ERP was 7.272 days (n = 11) versus 3.348 days (n = 23) (P = 0.004) for ERP. LOS was also compared to national CMS data. The LOS at HCH for DRG 329 improved from the 10th to 90th percentile (n = 238,907); DRG 330 improved from the 10th to the 72nd percentile (n = 285,423); DRG 331 improved from 10th to 54th percentile (n = 126,941) (P < 0.001). The RA at HCH in ERP and non-ERP cases was 3% at 30 and 90 days. CMS RA for DRG 329 was 25.1% at 90 days and 9.9% at 30 days; DRG 330 RA was 18.3% at 90 days and 6.6% at 30 days; DRG 331 RA was 11% at 90 days and 3.9% at 30 days. Conclusion: Implementation of ERP following bowel surgery at HCH significantly improved outcomes, in comparison to non-ERP cases, national CMS data, and Humana data. Further research on ERP for other fields and its impact on outcomes in other community settings is recommended.

Remediation of soil contaminated with PAHs and γ-HCH using Fenton oxidation activated by carboxymethyl cellulose-modified iron oxide-biochar.

The remediation of soil contaminated with hydrophobic organic pollutants has attracted great public concern. In the present study, a novel catalyst using biochar supported ferro ferric oxide modified by carboxymethyl cellulose (CMC-Fe3O4/BC) was developed to activate the Fenton reaction for hazardous hydrophobic organic pollutants, and the degradation mechanisms were analyzed in terms of free radicals, electron transfer pathways and degradation intermediates. The results showed that the CMC-Fe3O4/BC-activated H2O2 system degraded nearly 100% of pyrene in the aqueous system after a 1440-min reaction. The catalyst was also applied to remediate industrial field soil contaminated with PAHs and γ-HCH. The removal rate of the total pollutants reached 61.1% after a 10-day reaction, which was higher than that of Fe3O4/BC without modification. CMC enabled the Fe3O4 particles to more equably distribute on the BC surface, further effectively activating H2O2 to generate more ⋅OH and forming different degradation products compared to the Fe3O4/BC. Additionally, the CMC-Fe3O4/BC-activated H2O2 system obviously enhanced electron transfer on the BC surface. Thus, the PAHs and γ-HCH could be degraded via electron transfer pathways.

HCH6-1, an antagonist of formyl peptide receptor-1, exerts anti-neuroinflammatory and neuroprotective effects in cellular and animal models of Parkinson's disease.

Microglial activation-induced neuroinflammation contributes to onset and progression of sporadic and hereditary Parkinson's disease (PD). Activated microglia secrete pro-inflammatory and neurotoxic IL-1ß, IL-6 and TNF-α, which subsequently promote neurodegeneration. Formyl peptide receptor-1 (FPR1) of CNS microglia functions as pattern recognition receptor and is activated by N-formylated peptides, leading to microglial activation, induction of inflammatory responses and resulting neurotoxicity. In this study, it was hypothesized that FPR1 activation of microglia causes loss of dopaminergic neurons by activating inflammasome and upregulating IL-1ß, IL-6 or TNF-α and that FPR1 antagonist HCH6-1 exerts neuroprotective effect on dopaminergic neurons. FPR1 agonist fMLF induced activation of microglia cells by causing activation of NLRP3 inflammasome and upregulation and secretion of IL-1ß, IL-6 or TNF-α. Conditioned medium (CM) of fMLF-treated microglia cells, which contains neurotoxic IL-1ß, IL-6 and TNF-α, caused apoptotic death of differentiated SH-SY5Y dopaminergic neurons by inducing mitochondrial oxidative stress and activating pro-apoptotic signaling. FPR1 antagonist HCH6-1 prevented fMLF-induced activation of inflammasome and upregulation of pro-inflammatory cytokines in microglia cells. HCH6-1 co-treatment reversed CM of fMLF-treated microglia-induced apoptotic death of dopaminergic neurons. FPR1 antagonist HCH6-1 inhibited rotenone-induced upregulation of microglial marker Iba-1 protein level, cell death of dopaminergic neurons and motor impairment in zebrafish. HCH6-1 ameliorated rotenone-induced microglial activation, upregulation of FPR1 mRNA, activation of NLRP3 inflammasome, cell death of SN dopaminergic neurons and PD motor deficit in mice. Our results suggest that FPR1 antagonist HCH6-1 possesses anti-neuroinflammatory and neuroprotective effects on dopaminergic neurons by inhibiting microglial activation and upregulation of inflammasome activity and pro-inflammatory cytokines.

Degradation Characteristics and Remediation Ability of Contaminated Soils by Using ß-HCH Degrading Bacteria.

Three degradation strains that can utilize ß-Hexachlorocyclohexanes (ß-HCH) as the sole carbon source were isolated from the soil substrate of constructed wetland under long-term ß-HCH stress, and they were named A1, J1, and M1. Strains A1 and M1 were identified as Ochrobactrum sp. and strain J1 was identified as Microbacterium oxydans sp. by 16S rRNA gene sequence analysis. The optimum conditions for degradation with these three strains, A1, J1, and M1, were pH = 7, 30 °C, and 5% inoculum amount, and the degradation rates of 50 µg/L ß-HCH under these conditions were 58.33%, 51.96%, and 50.28%, respectively. Degradation characteristics experiments showed that root exudates could increase the degradation effects of A1 and M1 on ß-HCH by 6.95% and 5.82%, respectively. In addition, the degradation bacteria A1 and J1 mixed in a ratio of 1:1 had the highest degradation rate of ß-HCH, which was 69.57%. An experiment on simulated soil remediation showed that the compound bacteria AJ had the best effect on promoting the degradation of ß-HCH in soil within 98 d, and the degradation rate of ß-HCH in soil without root exudates was 60.22%, whereas it reached 75.02% in the presence of root exudates. The addition of degradation bacteria or degradation bacteria-root exudates during soil remediation led to dramatic changes in the community structure of the soil microorganisms, as well as a significant increase in the proportion of aerobic and Gram-negative bacterial groups. This study can enrich the resources of ß-HCH degrading strains and provided a theoretical basis for the on-site engineering treatment of ß-HCH contamination.

P-doped biochar regulates nZVI nanocracks formation for superefficient persulfate activation.

In this study, a novel P-doped biochar loaded with nano zero-valent iron (nZVI) composite (nZVI@P-BC), with abundant nanocracks from inside to outside in nZVI particles, was designed for ultra-efficient persulfate (PS) activation and gamma-hexachlorocyclohexane (γ-HCH) degradation. Results showed that P-doping treatment significantly enhanced specific surface area, hydrophobicity and adsorption capacity of biochar. Systematic characterizations revealed that the additional electrostatic stress and continuously generated multiple new nucleation sites of P-doped biochar were the main mechanism for the formation of nanocracked structure. nZVI@P-BC with KH2PO4 as P precursor showed superefficient PS activation and γ-HCH degradation, by which 92.6 % of 10 mg/L γ-HCH was removed within 10 min using 1.25 g/L catalyst and 4 mM PS, being 10.5-fold greater than that of without P-doping. Electron spin resonance and radical quenching test showed that •OH and 1O2 were the dominant active species, and further revealed that the unique nanocracked nZVI, high adsorption capacity and abundant P sites in nZVI@P-BC enhanced their generation and mediated extra direct surface electron transfer. nZVI@P-BC also exhibited high tolerance to different anions, humic acid and wide pH conditions. This work provides a new strategy and mechanism insight for the rational design of nZVI and diversified application of biochar.

Cross-sectional associations of persistent organic pollutants measured in adipose tissue and metabolic syndrome in clinically diagnosed middle-aged adults.

INTRODUCTION: Although often overlooked in clinical settings, accumulation of persistent organic pollutants (POPs) in visceral adipose tissue (VAT) is thought to be a relevant risk factor for metabolic syndrome (MetS). METHODS: One hundred and seventeen patients undergoing non-oncological surgery were randomly recruited and classified as MetS + if presented 3 out of the 5 MetS components: waist circumference (WC), systolic and diastolic blood pressure (SBP and DBP, respectively), serum glucose, insulin, triglycerides (TG) and high-density lipoprotein (HDL) cholesterol levels, according International Diabetes Federation (IDF) criteria. Seventeen organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in adipose tissue samples. Linear, logistic and weighted quantile sum (WQS) regression models, adjusted for age and sex, were performed. RESULTS: One third of the participants were males (36.8%) with a median age of 44 years, showing clinical evidences of MetS (35.0%). Adjusted linear regression models showed that WC correlated positively with all OCP concentrations. Higher fasting serum glucose levels were related to higher HCB and γ-HCH concentrations. The remaining OCPs and PCBs were not associated with this MetS component. HCB was inversely associated with HDL cholesterol levels, while PCB-180 was positively associated. HCB and γ-HCH concentrations were also positively correlated with DBP and SBP levels. PCB-138 was also positively associated with SBP. Adjusted logistic models revealed that exposure to HCB and γ-HCH were associated with increased odds of MetS [ORs (95%CI) 1.53 (1.22-1.92) and 1.39 (1.10-1.76) respectively; p < 0.01]. No associations were observed for the remaining POPs. WQS models showed a positive and significant mixture effect of POPs on the odds of MetS (exp [beta] = 2.34; p < 0.001), with γ-HCH (52.9%), o,p'-DDT (26.9%) and HCB (19.7%) driving the association. CONCLUSIONS: Our findings support that POPs accumulated in VAT, specifically HCB and (gamma)-HCH, are associated with both isolated components and clinically diagnosed SMT.

Compound-specific stable isotope analysis for characterization of the transformation of γ-HCH induced by biochar.

The role of biochar as the redox catalyst in the removal of reductive pollutants from soil and water system has been extensively studied recently, but there is still a lack of qualitative description of its specific mechanisms in redox processes. In this study, the mechanism of biochar in the transformation process of γ-HCH under anoxic condition was revealed by the compound-specific isotope analysis. The concentration and carbon isotopic composition (δ13C) of γ-HCH were detected in the treatments with different initial concentrations of γ-HCH and biochar materials with different redox properties and varied doses. The surface functional groups and electrochemical properties of biochar before and after the reaction were also characterized. The addition amount of biochar could affect the reduction of γ-HCH concentration, which were 59.1%, 34.6% and 22.4% in treatments with the addition of 5%, 1% and 0.2% biochar, respectively. Meanwhile, the δ13C value of γ-HCH also increased from -26.6 ± 0.2‰ to -23.8 ± 0.2‰ with the addition amount of biochar, especially in the treatment with 5% biochar. As evidenced by X-ray diffraction analysis and electrochemical analysis, biochar promoted the adsorption and transformation of γ-HCH simultaneously, and the oxygen-containing functional groups on the surface of biochar played an important role in the redox process. The isotopic fractionation value (εC) of γ-HCH transformation by biochar was first reported as -3.4 ± 0.4‰. The results will enable the quantitative description of the transformation degree of organic pollutants induced by biochar, and provide a new approach for evaluating the in-situ remediation effects of biochar in a complex environment.