County-Level Atrazine Use and Gastroschisis.

Importance: The incidence of gastroschisis, a birth defect involving the herniation of the small bowel through the abdominal wall, has increased in the US since the 1960s. The pesticide atrazine is a hypothesized cause of gastroschisis; however, examination of the association between atrazine and gastroschisis has been limited. Objective: To evaluate national trends in gastroschisis incidence, maternal and infant characteristics associated with gastroschisis, and whether county-level atrazine use is associated with gastroschisis. Design, Setting, and Participants: This retrospective, repeated cross-sectional study examined birth certificate data of all live births in the US and data on atrazine use from the US Geological Survey from January 1, 2009, through December 31, 2019. The data analysis was performed between August 5, 2021, and May 26, 2023. Exposures: County-level atrazine use. Main Outcomes and Measures: The primary outcome was gastroschisis incidence. Covariates included maternal age, race and ethnicity, body mass index (measured by weight in kilograms divided by height in meters squared), parity, insurance type, Chlamydia infection during pregnancy, smoking, and rurality. Mixed-effects logistic regression models (year fixed effects and county random effects) were constructed using different county-level atrazine exposure variables (1-, 5-, and 10-year means). Results: Between 2009 and 2019, 39 282 566 live births were identified, with 10 527 infant diagnoses of gastroschisis. Infants with gastroschisis were more likely to have mothers who identified as non-Hispanic White (61% vs 54%; P < .001), had a lower body mass index (median [IQR], 23.4 [20.8-27.2] vs 25.4 [22.0-30.8]; P < .001), were more likely to be nulliparous (median [IQR], 0 [0-1] vs 1 [0-2]; P < .001), and were more commonly covered by Medicaid (63% vs 43%; P < .001). During the study period, the rate (per 1000 live births) of gastroschisis decreased from 0.31 (95% CI, 0.29-0.33) to 0.22 (95% CI, 0.21-0.24). The median (IQR) county-level atrazine use estimates were higher among infants with gastroschisis (1 year, 1389 [IQR, 198-10 162] vs 1023 [IQR, 167-6960] kg; 5 years, 1425 [IQR, 273-9895] vs 1057 [IQR, 199-6926] kg; 10 years, 1508 [IQR, 286-10 271] vs 1113 [IQR, 200-6650] kg; P < .001). In adjusted models, higher county levels of atrazine (each 100 000-kg increase) were associated with a higher incidence of gastroschisis (1 year: adjusted odds ratio [AOR], 1.12 [95% CI, 1.01-1.24]; 5 years: AOR, 1.15 [95% CI, 1.02-1.30]; 10 years: AOR, 1.21 [95% CI, 1.07-1.38]). Conclusions and Relevance: In this cross-sectional study, higher county levels of atrazine were associated with infant diagnoses of gastroschisis. While atrazine is the second-most used herbicide in the US, numerous countries around the world have banned it out of concern for adverse effects on human health. These findings suggest that exploring alternatives to atrazine in the US may be warranted.

The Association of Agent Orange Exposure with the progression of monoclonal gammopathy of undetermined significance to multiple myeloma: a population-based study of Vietnam War Era Veterans.

Herbicide and pesticide exposure [e.g., agent orange (AO)] is associated with an increased risk of multiple myeloma (MM) due to the contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, it is unclear whether TCDD/AO exposure (AO exposure hereafter) increases the risk of progression of monoclonal gammopathy of undetermined significance (MGUS) to MM. We sought to evaluate the association in a nationwide study of US Veterans. A natural language processing algorithm was used to confirm MGUS and progression to MM. We included Veterans who were diagnosed with MGUS from 10/1/1999 to 12/31/2021 and served during the Vietnam War Era from 1/9/1962 to 5/7/1975. AO exposure was stratified according to three TCDD exposure levels: high (1/9/1962-11/30/1965), medium (12/1/1965-12/31/1970), or low (1/1/1971-5/7/1975). The association between AO exposure and progression was analyzed using multivariable Fine-Gray subdistribution hazard model with death as a competing event. The analytic cohort included 10,847 Veterans with MGUS, of whom 26.3% had AO exposure and 7.4% progressed to MM over a median follow-up of 5.2 years. In multivariable analysis, high exposure was associated with an increased progression rate (multivariable-adjusted hazard ratio 1.48; 95% confidence interval 1.02-2.16), compared to Veterans with no exposure. This information is critical to inform progression risk in patients diagnosed with MGUS and prior AO exposure. It is also applicable to MGUS patients with occupational TCDD exposure from herbicides and pesticides.

Urinary glyphosate levels and association with mortality in the 2013-16 National Health and Nutrition Examination Survey.

OBJECTIVES: Glyphosate is the most commonly used herbicide in the USA; however, its safety is still under debate. We assessed glyphosate levels and their association with overall mortality in a representative sample of the US adult population from the 2013 to 2016 National Health and Nutrition Examination Survey. METHODS: We extracted data on urinary glyphosate (N = 2910) measured by ion chromatography isotope-dilution tandem mass spectrometry. Associations between glyphosate concentrations and demographic, lifestyle and other exposures were analyzed. Data were linked to public-use Mortality Files for 2019. RESULTS: The mean (STD) glyphosate level was 0.53 (0.59) ng/ml, with 25.7% of the subjects having glyphosate levels at or below the detection limit. At multivariate analysis, age and creatinine were associated with glyphosate urinary levels (both P < 0.0001). There was a borderline association between glyphosate levels and mortality (HRadj 1.33; 95% CI 0.99-1.77 P = 0.06). When 3,5,6-trichloropyridinol was excluded from the Cox model, glyphosate exhibits a significant association with mortality (HRadj 1.33; 95% CI 1.00-1.77; P = 0.0532). CONCLUSIONS: These nationally representative data suggest that recent exposure to glyphosate could be associated with increased mortality. More studies are necessary to understand population-level risk associated with the product, given its widespread use in agriculture.

Exposure to phenoxyacetic acids and glyphosate as risk factors for non-Hodgkin lymphoma- pooled analysis of three Swedish case-control studies including the sub-type hairy cell leukemia.

The association between pesticide exposure and non-Hodgkin lymphoma (NHL) including hairy cell leukemia (HCL) was analyzed in a pooled study of three case-control studies. Results on exposure to pesticides were based on 1,425 cases and 2,157 controls participating in the studies. Exposures were assessed by self-administered questionnaires completed as needed by phone. In the pooled univariate analyses adjusted by age, gender and year of diagnosis, exposure to herbicides of the phenoxyacetic acid type yielded statistically significant increased risk with odds ratio (OR) = 1.9, 95% confidence interval CI) = 1.4-2.5. The herbicide glyphosate gave OR = 2.2, 95% CI = 1.3-3.8. Impregnating agents increased the risk. No clear dose-response effect was seen. OR was highest in the >10-20 years latency group for herbicides and impregnating agents. In the multivariate analysis including main pesticide groups, statistically significant increased risk was found for herbicides, OR = 1.6, 95% CI = 1.2-2.1 and impregnating agents with OR = 1.4, 95% CI = 1.1-1.8. This analysis confirmed an association between NHL including HCL and exposure to certain herbicides.

Glyphosate exposure and urinary oxidative stress biomarkers in the Agricultural Health Study.

BACKGROUND: Glyphosate is the most widely applied herbicide worldwide, and its use has been associated with increased risks of certain hematopoietic cancers in epidemiologic studies. Animal and in vitro experiments suggest that glyphosate may induce oxidative stress, a key characteristic of carcinogens; however, evidence in human populations remains scarce. We investigated associations between glyphosate exposure and urinary oxidative stress biomarkers in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiologic subcohort in the Agricultural Health Study. METHODS: This analysis included 268 male farmers selected based on self-reported recent and lifetime occupational glyphosate use and 100 age- and geography-matched male nonfarmers. Concentrations of glyphosate and oxidative stress biomarkers (8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-iso-prostaglandin-F2α, and malondialdehyde [MDA]) were quantified in first-morning-void urine. We performed multivariable linear regression to evaluate associations of urinary glyphosate and self-reported glyphosate use with each oxidative stress biomarker. RESULTS: Urinary glyphosate concentrations were positively associated with levels of 8-OHdG (highest vs lowest glyphosate quartile; geometric mean ratio = 1.15, 95% confidence interval = 1.03 to 1.28; Ptrend = .02) and MDA (geometric mean ratio = 1.20, 95% confidence interval = 1.03 to 1.40; Ptrend = .06) overall. Among farmers reporting recent glyphosate use (last 7 days), use in the previous day was also associated with statistically significantly increased 8-OHdG and MDA levels. Compared with nonfarmers, we observed elevated 8-iso-prostaglandin-F2α levels among farmers with recent, high past 12-month, or high lifetime glyphosate use. CONCLUSIONS: Our findings contribute to the weight of evidence supporting an association between glyphosate exposure and oxidative stress in humans and may inform evaluations of the carcinogenic potential of this herbicide.

Normalized difference vegetation index for desiccation evaluation with glyphosate + 2, 4-D in magnetized spray solution / Índice de vegetação por diferença normalizada para avaliação de dessecação com glyphosate + 2, 4-D em calda magnetizada

Water magnetization and geoprocessing are increasingly utilized tools in weed management. Our objective was to study the influence of water magnetization on herbicide efficiency and to verify whether there is a relationship between control scores and the normalized difference vegetation index (NDVI). In the laboratory experiment, water was subjected to magnetization and evaluated with respect to four characteristics. In the field experiment, plots of Brachiaria grass were subjected to treatments in a factorial scheme (6 × 2 + 1). Six herbicidal factors (doses of glyphosate and glyphosate + 2,4-D) and the magnetization or absence of magnetization of the spray solution were evaluated and compared against the control treatment (without spraying). Weed control assessments were carried out six times. Images were obtained using an embedded multispectral camera to determine the NDVI values. Data related to water characteristics were analyzed using the t test. Weed control and NDVI data were subjected to analysis of variance and are presented in regression graphs. Dispersion analysis of NDVI data was performed according to the control scores. The magnetization process decreased the pH of the water and increased the surface tension, but it did not influence the control scores or the NDVI. As the glyphosate dose was increased, the control scores were higher and the NDVI values were lower. Magnetized water did not affect the biological efficiency of the herbicides, and there was a strong correlation between the control scores and the NDVI values.

A magnetização da água e o geoprocessamento são ferramentas cada vez mais utilizadas no manejo de ervas daninhas. Nosso objetivo foi estudar a influência da magnetização da água na eficiência do herbicida e verificar se existe uma relação entre os escores de controle e o índice de vegetação por diferença normalizada (NDVI). No experimento de laboratório, a água foi submetida à magnetização e avaliada em relação a quatro características. No experimento de campo, parcelas de capim-braquiária foram submetidas a tratamentos em esquema fatorial (6 × 2 + 1). Seis fatores herbicidas (doses de glyphosate e glyphosate + 2,4-D) e a magnetização ou ausência de magnetização da calda foram avaliados e comparados com o tratamento controle (sem pulverização). Avaliações de controle de plantas daninhas foram realizadas seis vezes. As imagens foram obtidas usando uma câmera multiespectral incorporada para determinar os valores de NDVI. Os dados relacionados às características da água foram analisados por meio do teste t. O controle de plantas daninhas e os dados de NDVI foram submetidos à análise de variância e são apresentados em gráficos de regressão. A análise de dispersão dos dados NDVI foi realizada de acordo com os escores de controle. O processo de magnetização diminuiu o pH da água e aumentou a tensão superficial, mas não influenciou nos escores de controle ou no NDVI. Conforme a dose de glyphosate foi aumentada, os escores de controle foram maiores e os valores de NDVI foram menores. A água magnetizada não afetou a eficiência biológica dos herbicidas, e houve uma forte correlação entre os escores de controle e os valores de NDVI.

Herbicide use in farming and other jobs in relation to non-Hodgkin's lymphoma (NHL) risk.

OBJECTIVES: Given mixed evidence for carcinogenicity of current-use herbicides, we studied the relationship between occupational herbicide use and risk of non-Hodgkin's lymphoma (NHL) in a large, pooled study. METHODS: We pooled data from 10 case-control studies participating in the International Lymphoma Epidemiology Consortium, including 9229 cases and 9626 controls from North America, the European Union and Australia. Herbicide use was coded from self-report or by expert assessment in the individual studies, for herbicide groups (eg, phenoxy herbicides) and active ingredients (eg, 2,4-dichlorophenoxyacetic acid (2,4-D), glyphosate). The association between each herbicide and NHL risk was estimated using logistic regression to produce ORs and 95% CIs, with adjustment for sociodemographic factors, farming and other pesticides. RESULTS: We found no substantial association of all NHL risk with ever-use of any herbicide (OR=1.10, 95% CI: 0.94 to 1.29), nor with herbicide groups or active ingredients. Elevations in risk were observed for NHL subtypes with longer duration of phenoxy herbicide use, such as for any phenoxy herbicide with multiple myeloma (>25.5 years, OR=1.78, 95% CI: 0.74 to 4.27), 2,4-D with diffuse large B-cell lymphoma (>25.5 years, OR=1.47, 95% CI: 0.67 to 3.21) and other (non-2,4-D) phenoxy herbicides with T-cell lymphoma (>6 years, lagged 10 years, OR=3.24, 95% CI: 1.03 to 10.2). An association between glyphosate and follicular lymphoma (lagged 10 years: OR=1.48, 95% CI: 0.98 to 2.25) was fairly consistent across analyses. CONCLUSIONS: Most of the herbicides examined were not associated with NHL risk. However, associations of phenoxy herbicides and glyphosate with particular NHL subtypes underscore the importance of estimating subtype-specific risks.

Leaching of saflufenacil in soils with different organic matter contents

Saflufenacil is a herbicide recommended for use in the main agricultural crops in Brazil to control eudicotyledonous weeds. However, the application of saflufenacil has been carried out without previous knowledge of this herbicide interactions with soil colloids, which may increase environmental contamination risks. In this study, the leaching of saflufenacil in soil samples was estimated with different organic matter contents. Therefore, PVC columns were filled with samples of Xanthic Ferralsol (XF) and Ferralsol (F), with different physical and chemical attributes. Twelve hours after herbicide (70 g i.a. ha-1) application, the PVC columns were subjected to a rainfall of 60 mm. For the evaluation of saflufenacil leaching, the columns were sectioned in ten parts with 5-cm each. Saflufenacil leached up to 50 and 40 cm deep in the samples, with the lowest contents of organic matter of XF and F, respectively. The increase in organic matter content of Ferralsol and Xanthic Ferralsol samples reduced saflufenacil leaching and the symptoms of intoxication in the indicator species. There was an inverse relation between the content of organic matter and the leaching of the herbicide in both soils studied. It was observed that the application of saflufenacil in soils with low organic matter contents may represent a significant environmental contamination risk of soils and watercourses.

Perinatal exposure to an aromatase inhibitor glyphosate-base herbicide reduced male and female social behavior in juvenile age and the sexual behavior at adult female rats / Exposição perinatal ao inibidor da aromatase a base de glifosato reduz o comportamento social de machos e fêmeas e o comportamento sexual de ratas

Objectives: The herbicide glyphosate, a pesticide used in agriculture to control weeds, both in food crops and in other agricultural areas, has been identified as an endocrine modulator through the inhibition of aromatase activity and the activation of estrogen receptors. The present study examined the effects of a glyphosate-based herbicide (Roundup® (GLY-BH) on sexual dimorphism of rats after perinatal exposure to low and high GLY-BH in males and females offspring. Methods: Two groups of pregnant rats were treated with two doses of GLY-BH (50 or 150 mg/kg) from day 15 of gestation (GD15) to postnatal day 7 (PND7). Play fighting behavior was observed at the juvenile stage and during social and sexual behaviors in adulthood. Results: Perinatal GLY-BH exposure reduced male and female body weight at 28, 75, and 90 days of age. The play fighting behavior was decreased in both sexes, but female rats were more affected. The sexual behaviors were reduced only in females. Conclusions: Perinatal exposure to both doses of GLY-BH promoted sexually dimorphic effects in both juvenile and adulthood stages. These effects were attributed to the inhibition of aromatase activity induced by exposure to GLY-BH in the perinatal period.(AU)

Objetivos: O glifosato é um herbicida não seletivo, usado em muitas culturas alimentares e não alimentares e em áreas não agrícolas, sendo que os produtos a base de glifosato atuam como moduladores das funções endócrinas por meio da inibição da atividade da aromatase e da ativação de receptores de estrógeno. O presente estudo avaliou os efeitos do herbicida Roundup® (GLY-BH) à base de glifosato, em comportamentos sexualmente dimórficos de ratos após exposição perinatal a doses baixas e altas de GLY-BH no período perinatal. Métodos: Ratas prenhas foram tratadas com 50 ou 150 mg/kg de GLY-BH do 15º dia de gestação (GD15) ao 7º dia de lactação (LD7). O comportamento de luta/brincar foi observado na fase juvenil e os comportamentos social e sexual na idade adulta. Resultados: a exposição perinatal a GLY-BH reduziu o peso corporal de machos e fêmeas aos 28, 75 e 90 dias de idade. O comportamento de luta/brincar diminuiu em ambos os sexos, sendo as ratas foram as mais afetadas. O comportamento sexual foi reduzido apenas nas fêmeas. Conclusões: A exposição perinatal a ambas as doses do GLY- BH promoveu tanto na idade juvenil como na idade adulta, efeitos sexualmente dimórficos. Esses efeitos foram atribuídos à inibição da atividade da aromatase induzida exposição perinatal ao GLY-BH.(AU)

Pleiotropic Outcomes of Glyphosate Exposure: From Organ Damage to Effects on Inflammation, Cancer, Reproduction and Development.

Glyphosate is widely used worldwide as a potent herbicide. Due to its ubiquitous use, it is detectable in air, water and foodstuffs and can accumulate in human biological fluids and tissues representing a severe human health risk. In plants, glyphosate acts as an inhibitor of the shikimate pathway, which is absent in vertebrates. Due to this, international scientific authorities have long-considered glyphosate as a compound that has no or weak toxicity in humans. However, increasing evidence has highlighted the toxicity of glyphosate and its formulations in animals and human cells and tissues. Thus, despite the extension of the authorization of the use of glyphosate in Europe until 2022, several countries have begun to take precautionary measures to reduce its diffusion. Glyphosate has been detected in urine, blood and maternal milk and has been found to induce the generation of reactive oxygen species (ROS) and several cytotoxic and genotoxic effects in vitro and in animal models directly or indirectly through its metabolite, aminomethylphosphonic acid (AMPA). This review aims to summarize the more relevant findings on the biological effects and underlying molecular mechanisms of glyphosate, with a particular focus on glyphosate's potential to induce inflammation, DNA damage and alterations in gene expression profiles as well as adverse effects on reproduction and development.

Thioredoxin-1 mediates neuroprotection of Schisanhenol against MPP+-induced apoptosis via suppression of ASK1-P38-NF-κB pathway in SH-SY5Y cells.

Oxidative stress-induced dopaminergic neuronal loss and apoptosis play a crucial role in the pathogenesis of Parkinson's disease (PD), and as a vital antioxidant protein, thioredoxin (Trx) exerts neuroprotection against PD. In this study, we investigated the effect of Schisanhenol (Sal), an active component from a traditional Chinese herb Schisandra rubriflora (Franch.), on MPP+-induced apoptosis and its association with thioredoxin-1 (Trx1) in SH-SY5Y cells. The protein levels of Trx1 and apoptosis-related proteins were detected by Western blot, the expression of Trx1 mRNA by real time qPCR, and apoptosis was detected by fluorescence microscopy and flow cytometry. Pretreatment with Sal (1 µM, 10 µM, and 50 µM) dose-dependently ameliorated MPP+-induced neuronal injury, confirmed by the improvement of the viability and morphological changes. Sal decreased the apoptosis rate of cells, suppressed the production of DNA ladder and sub-G1 peak, inhibited the Caspase-3 activity and the expression of apoptosis-related proteins. Sal enhanced the expression of Trx1 both in the protein and mRNA levels. However, the Trx1 inhibitor PX-12 suppressed the protective effects of Sal. In addition, Sal inhibited NF-κB translocation and activation. These results suggest that Sal has a protective effect against MPP+-induced apoptosis in SH-SY5Y cells via up-regulation of Trx1 expression and suppression of ASK1-P38-NF-κB pathway.

Naringenin alleviates paraquat-induced dopaminergic neuronal loss in SH-SY5Y cells and a rat model of Parkinson's disease.

Parkinson's disease (PD), a common neurodegenerative disease is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. The cause of dopaminergic loss in PD remains unknown for a long time, however, recent reports suggest oxidative stress plays a key role in the pathogenesis of PD. Paraquat (PQ), a widely used herbicide is an oxidative stress inducer that has been implicated as a potential risk factor for the development of PD. Flavonoids are naturally occurring polyphenolic compounds that display a variety of therapeutic properties against oxidative stress. Naringenin (NAR), a natural flavonoid, exhibits neuroprotection against PD-related pathology. However, studies on its neuroprotective role and the underlying mechanisms are scarce, therefore the present study explored the potential neuroprotective role of NAR in PQ-induced parkinsonism in SH-SY5Y cells and rat model. The effect of NAR on PQ-induced cellular toxicity was determined by measuring cell viability, oxidative stress, ATP levels and the same effect was determined by assessing behavioral, biochemical, immunohistochemical, qRT-PCR and Western blot in rat model. NAR treatment in SH-SY5Y cells resulted in increased cell viability, reduced oxidative stress, elevated mitochondrial membrane potential, and higher cellular ATP levels. In rats, NAR treatment resulted in significant neuroprotection against PQ-induced behavioral deficits, oxidative stress, mitochondrial dysfunction, and astrocytosis. NAR treatment significantly modulated PQ-induced mRNA expressions of DRD2, DAT, LRRK2, SNCA, ß-catenin, caspase-3, BDNF genes. NAR treatment increased TH protein expression and modulated its immunoreactivity in rat striatum. Also, GFAP decreased in response to NAR treatment. So, in the present study, NAR exhibits neuroprotection against PQ-induced neurotoxicity and neurodegeneration indicating its novel therapeutic potential against PD.

Systemic inflammation and oxidative stress induced by inhaled paraquat in rat improved by carvacrol, possible role of PPARγ receptors.

Control rats were exposed to saline aerosol, two groups were exposed to paraquat (PQ), 27 (PQ-L) and 54 (PQ-H) mg/m3 aerosols and six groups were treated with carvacrol, 20 (C-L) and 80 (C-H) mg/kg/day, pioglitazone, 5 (Pio-L) and 10 (Pio-H) mg/kg/day, C-L+Pio-L and dexamethasone, 0.03 mg/kg/day, for 16 days after the end of exposure to PQ-H. Different variables were measured after the end of treatment period. Total and differential white blood cells counts, nitrite, malondialdehyde, interleukin (IL)-10, and interferon-gamma levels were significant increased, but thiol, superoxide dismutase, catalase, IL-17, and tumor necrosis factor alpha were decreased in the blood due to both doses of PQ (p < 0.05-p < 0.001). Most measured parameters were significantly improved in treated groups with both doses of carvacrol, pioglitazone, the combination of C-L+Pio-L and dexamethasone compared to PQ-H group (p < 0.05-p < 0.001). Treatment with C-L+Pio-L showed significantly higher effects compared to each one alone (p < 0.05-p < 0.001). Systemic oxidative stress and inflammation due to inhaled PQ were improved by carvacrol and pioglitazone. Higher effects of C-L+Pio-L than each one alone suggests carvacrol modulating PPAR-γ receptors.

A Review and Update with Perspective of Evidence that the Herbicide Glyphosate (Roundup) is a Cause of Non-Hodgkin Lymphoma.

Glyphosate-based formulations (GBFs), such as Roundup, are the most heavily used herbicides in the world. In 2015, the International Agency for Research on Cancer (IARC) concluded that glyphosate and GBFs are probably carcinogenic to humans (group 2A), mainly for non-Hodgkin lymphoma (NHL). However, this finding has been controversial, and most pesticide regulatory agencies have not followed their lead. The purpose of this review was to examine the scientific literature linking exposure to glyphosate and GBFs to the development of NHL, with emphasis on new findings since publication of the IARC report. The epidemiologic studies provide ample evidence for an association between exposure to GBFs and an increased risk of NHL. Animal studies have shown that glyphosate is carcinogenic in rodents and causes NHL in mice. Mechanistic studies have demonstrated that glyphosate and GBFs are genotoxic to human lymphocytes, the normal cell of origin of NHL, both in vitro and in vivo. Genotoxic and other biological effects have also been shown in various animal and cell models with these agents even at low doses. A novel mechanism underlying the specificity of glyphosate for NHL, that is upregulation of the B-cell genome mutator enzyme activation-induced cytidine deaminase, has recently been demonstrated. These findings were evaluated holistically using the guidelines for evaluation of general causation set forth by Bradford Hill. This evaluation provides coherent and compelling evidence that glyphosate and GBFs are a cause of NHL in humans exposed to these agents. These findings should prompt new reviews by pesticide regulatory agencies around the world.

Environmental and economic concerns surrounding restrictions on glyphosate use in corn.

Since the commercialization of transgenic glyphosate-tolerant (GT) crops in the mid-1990s, glyphosate has become the dominant herbicide to control weeds in corn, soybean, and other crops in the United States and elsewhere. However, recent public concerns over its potential carcinogenicity in humans have generated calls for glyphosate-restricting policies. Should a policy to restrict glyphosate use, such as a glyphosate tax, be implemented? The decision involves two types of tradeoffs: human health and environmental (HH-E) impacts versus market economic impacts, and the use of glyphosate versus alternative herbicides, where the alternatives potentially have more serious adverse HH-E effects. Accounting for farmers' weed management choices, we provide empirical evaluation of the HH-E welfare and market economic welfare effects of a glyphosate use restriction policy on US corn production. Under a glyphosate tax, farmers would substitute glyphosate for a combination of other herbicides. Should a 10% glyphosate tax be imposed, then the most conservative welfare estimate is a net HH-E welfare gain with a monetized value of US$6 million per annum but also a net market economic loss of US$98 million per annum in the United States, which translates into a net loss in social welfare. This result of overall welfare loss is robust to a wide range of tax rates considered, from 10 to 50%, and to multiple scenarios of glyphosate's HH-E effects, which are the primary sources of uncertainties about glyphosate's effects.

Chloroplast-derived photo-oxidative stress causes changes in H2O2 and EGSH in other subcellular compartments.

Metabolic fluctuations in chloroplasts and mitochondria can trigger retrograde signals to modify nuclear gene expression. Mobile signals likely to be involved are reactive oxygen species (ROS), which can operate protein redox switches by oxidation of specific cysteine residues. Redox buffers, such as the highly reduced glutathione pool, serve as reservoirs of reducing power for several ROS-scavenging and ROS-induced damage repair pathways. Formation of glutathione disulfide and a shift of the glutathione redox potential (EGSH) toward less negative values is considered as hallmark of several stress conditions. Here we used the herbicide methyl viologen (MV) to generate ROS locally in chloroplasts of intact Arabidopsis (Arabidopsis thaliana) seedlings and recorded dynamic changes in EGSH and H2O2 levels with the genetically encoded biosensors Grx1-roGFP2 (for EGSH) and roGFP2-Orp1 (for H2O2) targeted to chloroplasts, the cytosol, or mitochondria. Treatment of seedlings with MV caused rapid oxidation in chloroplasts and, subsequently, in the cytosol and mitochondria. MV-induced oxidation was significantly boosted by illumination with actinic light, and largely abolished by inhibitors of photosynthetic electron transport. MV also induced autonomous oxidation in the mitochondrial matrix in an electron transport chain activity-dependent manner that was milder than the oxidation triggered in chloroplasts by the combination of MV and light. In vivo redox biosensing resolves the spatiotemporal dynamics of compartmental responses to local ROS generation and provides a basis for understanding how compartment-specific redox dynamics might operate in retrograde signaling and stress acclimation in plants.

Cloning and Characterization of 5-enopy ruvylshikimate-3-phosphate Synthase from Fragaria vesca

Abstract To discover and isolate a glyphosate-resistant gene from Fragaria vesca through gene mining. An open reading frame (ORF) of 1563 bp encoding EPSPSwas amplified from Fragaria vesca (FvEPSPS). FvEPSPS (Genebank: XP004306932.1) encodes a polypeptide of 520 amino acids and it has hightly homologous with EPSPS from other plants. qRT-PCR analysis showed that the FvEPSPS was expressed extensively in all tissues including leaves, roots and stems, with higher expression in leaves. Furthermore, transgenic Arabidopsis Thaliana exhibited 10 mM glyphosate to resistance. Therefore, this research offers a new glyphosate-resistant gene for development of transgenic crops.

New Lead Discovery of Herbicide Safener for Metolachlor Based on a Scaffold-Hopping Strategy.

The use of herbicide safeners can significantly alleviate herbicide injury to protect crop plants and expand the application scope of the existing herbicides in the field. Sanshools, which are well known as spices, are N-alkyl substituted compounds extracted from the Zanthoxylum species and have several essential physiological and pharmacological functions. Sanshools display excellent safener activity for the herbicide metolachlor in rice seedlings. However, the high cost of sanshools extraction and difficulties in the synthesis of their complicated chemical structures limit their utilization in agricultural fields. Thus, the present study designed and synthesized various N-alkyl amide derivatives via the scaffold-hopping strategy to solve the challenge of complicated structures and find novel potential safeners for the herbicide metolachlor. In total, 33 N-alkyl amide derivatives (2a-k, 3a-k, and 4a-k) were synthesized using amines and saturated and unsaturated fatty acids as starting materials through acylation and condensation. The identity of all the target compounds was well confirmed by 1H-NMR, 13C-NMR, and high-resolution mass spectrometry (HRMS). The primary evaluation of safener activities for the compounds by the agar method indicated that most of the target compounds could protect rice seedlings from injury caused by metolachlor. Notably, compounds 2k and 4k displayed excellent herbicide safener activities on plant height and demonstrated relatively similar activities to the commercialized compound dichlormid. Moreover, we showed that compounds 2k and 4k had higher glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and polyphenol oxidase (PPO) activities in rice seedlings, compared to the metolachlor treatment. In particular, 2k and 4k are safer for aquatic organisms than dichlormid. Results from the current work exhibit that compounds 2k and 4k have excellent crop safener activities toward rice and can, thus, be promising candidates for further structural optimization in rice protection.

Hydrogen sulfide alleviates oxidative stress injury and reduces apoptosis induced by MPP+ in Parkinson's disease cell model.

Hydrogen sulfide (H2S), an endogenously produced gas, is a cardioprotective agent against neurotoxin-induced neurodegeneration in Parkinson's disease (PD). However, the roles of H2S in 1-methyl-4-phenylpyridinium ion (MPP+)-treated SH-SY5Y cells with the involvement of reactive oxygen species-nitric oxide (ROS-NO) signaling pathway in PD remain unclear. For this study, a MPP+-treated SH-SY5Y cell model was established to explore the regulatory role of H2S in oxidative stress injury and cell apoptosis. With the cell viability, apoptosis, cytotoxicity, levels of reactive oxygen species (ROS) and nitric oxide (NO), mitochondrial transmembrane potential (Δψm), contents of oxidative stress injury-related markers (glutathione, superoxide dismutase, malondialdehyde), levels of apoptosis-related proteins (Caspase 3, Bax, Bcl-2) and inducible nitric oxide synthase (iNOS) determined, this study demonstrated that NaHS (an H2S donor) treatment could alleviated the reduction of cell viability and cytotoxicity, cell apoptosis, Δψm loss, contents of ROS and NO, and oxidative stress injury induced by MPP+. The present study showed that H2S may protect SH-SY5Y cells from MPP+-induced injury in PD cell model via the inhibition of ROS-NO signaling pathway and provide insight into the potential of H2S for PD therapy.

Pterostilbene as a protective antioxidant attenuates diquat-induced liver injury and oxidative stress in 21-day-old broiler chickens.

This study investigated the effects of pterostilbene (PT) supplementation on growth performance, hepatic injury, and antioxidant variables in a broiler chicken model with diquat (DQ)-induced oxidative stress. There were 192 one-day-old male Ross 308 broiler chicks randomly allocated to one of two treatment groups: 1) broilers fed a basal diet and 2) broilers fed a diet supplemented with 400 mg/kg PT. At 20 D of age, half of the broilers in each group were intraperitoneally injected with DQ (20 mg per kg BW), whereas the other half were injected with an equivalent amount of sterile saline. Diquat induced a rapid loss of BW (P < 0.001) 24 h post-injection, but dietary PT supplementation improved the BW change of broilers (P = 0.014). Compared with unchallenged controls, the livers of DQ-treated broilers were in severe cellular damage and oxidative stress, with the presence of higher plasma transaminase activities (P < 0.05), a greater number of apoptotic hepatocytes (P < 0.001), and an increased malondialdehyde content (P = 0.007). Pterostilbene supplementation prevented the increases in plasma aspartate aminotransferase activity (P = 0.001), the percentage of hepatocyte apoptosis (P < 0.001), and the hepatic malondialdehyde accumulation (P = 0.011) of the DQ-treated broilers. Regarding the hepatic antioxidant function, PT significantly increased total antioxidant capacity (P = 0.007), superoxide dismutase activity (P = 0.016), reduced glutathione content (P = 0.011), and the ratio of reduced glutathione to oxidized glutathione (P = 0.003), whereas it reduced the concentration of oxidized glutathione (P = 0.017). Pterostilbene also boosted the expression levels of nuclear factor erythroid 2-related factor 2 (P = 0.010), heme oxygenase 1 (P = 0.037), superoxide dismutase 1 (P = 0.014), and the glutamate-cysteine ligase catalytic subunit (P = 0.001), irrespective of DQ challenge. In addition, PT alleviated DQ-induced adenosine triphosphate depletion (P = 0.010). In conclusion, PT attenuates DQ-induced hepatic injury and oxidative stress of broilers presumably by restoring hepatic antioxidant function.