Advance of Metformin in Liver Disease.

Metformin is a first-line drug for the treatment of type 2 diabetes with a good safety profile and relatively low cost. In recent years, many other effects of metformin have been discovered. In this review, we provide the research advances in metformin in liver disease. High-dose metformin can activate AMPK by inhibiting mitochondrial complex 1. In addition, low-dose metformin could activate lysosomal AMPK through PEN2. Activated AMPK can reduce fatty acid synthesis, inhibit tumor proliferation and metastasis, and reshape the tumor microenvironment. In addition, metformin can reduce ROS production by inhibiting mitochondrial complex 1, which can reduce liver damage. Therefore, metformin has been found to alleviate nonalcoholic fatty liver disease and cirrhosis, relieve liver damage, and reduce the incidence of hepatocellular carcinoma and cholangiocarcinoma. This information suggests that metformin may represent a new possibility for the prevention and treatment of liver diseases.

An automatic progressive chromosome segmentation approach using deep learning with traditional image processing.

The fully automatic chromosome analysis system plays an important role in the detection of genetic diseases, which in turn can reduce the diagnosis burden for cytogenetic experts. Chromosome segmentation is a critical step for such a system. However, due to the non-rigid structure of chromosomes, chromosomes may curve in any direction, and two or more chromosomes may touch or overlap to form unpredictable chromosome clusters in metaphase chromosome images, leading to automatic chromosome segmentation as a challenge. In this paper, we propose an automatic progressive segmentation approach to perform the entire metaphase chromosome image segmentation using deep learning with traditional image processing. It follows three stages. In the first stage, thresholding-based and geometric-based methods are employed to divide all chromosomes as single ones and chromosome clusters. To tackle the segmentation for unpredictable chromosome clusters, we first present a new chromosome cluster identification network named CCI-Net to classify all chromosome clusters into different types in the second stage, and then in the third stage, we combine traditional image processing with deep CNNs to accomplish chromosome instance segmentation from different types of clusters. Evaluation results on a clinical dataset of 1148 metaphase chromosome images show that the proposed automatic progressive segmentation method achieves 94.60% chromosome cluster identification accuracy and 99.15% instance segmentation accuracy. The experimental results exhibit that our proposed approach can effectively identify chromosome clusters and successfully perform fully automatic chromosome segmentation.

Bi2O2Se-Based Bimode Noise Generator for the Application of Generative Adversarial Networks.

In the emerging technology, the generative aversive networks (GANs), randomness, and unpredictability of inputting noises are the keys to the uniqueness, diversity, robustness, and security of the generated images. Compared with deterministic software-based noise generation, hardware-based noise generation introduces physical entropy sources, such as electronic and photonic noises, to add unpredictability. In this study, bimode Bi2O2Se-based noise generators have been demonstrated for the application of GANs. Harnessing its ultrahigh carrier mobility, excellent air stability, marvelous optoelectronic performance, as well as the unique surface resistive switching effect and defect locations in the energy diagram, Bi2O2Se provides a good material platform to easily integrate with multiple device architectures for generating noises in different physical sources. The noise of the black current mode in a photodetector architecture and the random telegraph noise in a memristor mode were measured, characterized, compared, and analyzed. A method of Markov chain equipped with K-means clustering was carried out to calculate the discrete noise states and the transition probability matrix between them. To evaluate the generated properties of the GANs based on the hardware noise source, the inception score and Fréchet inception distance were evaluated.

Mixed exposure to phenol, parabens, pesticides, and phthalates and insulin resistance in NHANES: A mixture approach.

PURPOSE: The effects of environmental chemicals on insulin resistance have attracted extensive attention. Previous studies typically focused on the single chemical effects. This study adopted three different models to analyze the mixed effects of nine common chemicals (one phenol, two parabens, two chlorophenols and four phthalates) on insulin resistance. METHODS: Urinary concentrations of chemicals were extracted from National Health and Nutrition Examination Survey (NHANES) 2009-2016. Insulin resistance was assessed using homeostatic model assessment (HOMA) and defined as HOMA-IR >2.6. The generalized linear regression (GLM), weighted quantile sum regression (WQS) and Bayesian kernel machine regression models (BKMR) were applied to assess the relationship between chemical mixture and HOMA-IR or insulin resistance. RESULTS: Of the 2067 participants included, 872 (42.19 %) were identified as insulin resistant. In single-chemical GLM model, di-2-ethylhexyl phthalate (DEHP) had the highest parameter (ß/OR, 95 % CIs) of 0.21 (quartile 4, 0.12- 0.29) and 1.95 (quartile 4, 1.39- 2.74). Similar results were observed in the multi-chemical models, with DEHP (quartile 4) showing the positive relationship with HOMA-IR (0.18, 0.08- 0.28) and insulin resistance (1.76, 1.17- 2.64). According to WQS models, the WQS indices were significantly positively correlated with both HOMA-IR (ß: 0.07, 95 % CI: 0.03- 0.12) and insulin resistance (OR: 1.25, 95 % CI: 1.03- 1.53). DEHP was the top-weighted chemical positively correlated with both HOMA-IR and insulin resistance. In the BKMR model, the joint effect was also positively correlated with both outcomes. DEHP remained the main contributor to the joint effect, consistent with WQS analysis. CONCLUSION: Our findings suggested that these chemical mixtures had the positive joint effects on both HOMA-IR and insulin resistance, with DEHP being the potentially predominant driver. The inter-validation of the three models may indicate that reducing the DEHP concentration could improve glucose homeostasis and reduce the risk of insulin resistance. However, further studies are recommended to deepen our findings and elucidate the mechanisms of insulin resistance and chemical mixture.

Mechanisms of Scaling Effect for Emerging Nanoscale Interconnect Materials.

The resistivity of Cu interconnects increases rapidly with continuously scaling down due to scatterings, causing a major challenge for future nodes in M0 and M1 layers. Here, A Boltzmann-transport-equation-based Monte Carlo simulator, including all the major scattering mechanisms of interconnects, is developed for the evaluation of electron transport behaviors. Good agreements between our simulation and the experimental results are achieved for Cu, Ru, Co, and W, from bulk down to 10 nm interconnects. The line resistance values of the four materials with the inclusion of liner and barrier thicknesses are calculated in the same footprint for a fair comparison. The impact of high aspect ratio on resistivity is analyzed for promising buried power rail materials, such as Ru and W. Our results show that grain boundary scattering plays the most important role in nano-scale interconnects, followed by surface roughness and plasma excimer scattering. Surface roughness scattering is the origin of the resistivity decrease for high-aspect-ratio conductive rails. In addition, the grain sizes for the technical nodes of different materials are extracted and the impact of grain size on resistivity is analyzed.

Combined exposure to multiple metals on serum uric acid in NHANES under three statistical models.

BACKGROUND: There are rare researches on the correlations between metals exposure and serum uric acid (SUA), and existing research has only investigated the single metal effect. This study aimed to investigate the combined effects of metal mixtures on SUA and hyperuricemia using three statistical models. METHODS: In this study, the data were extracted from three cycle years of the National Health and Nutrition Examination Survey (NHANES). Subsequently, generalized linear regression, weighted quantile regression (WQS) and Bayesian kernel machine regression (BKMR) models were fitted to evaluate the correlations between metal mixtures and both SUA and hyperuricemia. RESULTS: Of 3926 participants included, 19.13% participants had hyperuricemia. It was found using multi-metals generalized linear regression models that there were positive correlations of arsenic and cadmium with both outcomes. The negative correlations were identified in cobalt, iodine, and manganese with SUA concentration, whereas only cobalt was negatively correlated with hyperuricemia. Based on the WQS regression model fitted in positive direction, it was suggested that the WQS indices were significantly correlated with SUA (ß = 6.64, 95% CI: 3.14-10.13) and hyperuricemia (OR = 1.25, 95% CI: 1.08-1.44); however, the result achieved by using the model fitted in negative direction indicated that the WQS indices were only significantly correlated with SUA (ß = -5.29, 95%CI: 8.02 âˆ¼ -2.56). With the use of the BKMR model, a significant increasing trend between metal mixtures and hyperuricemia was found, while no significant overall effect of metal mixtures on SUA was identified. The predominant roles of arsenic, cadmium, and cobalt in the change of SUA and hyperuricemia risk were found using all three models. CONCLUSION: The finding of this study revealed that metal mixtures might have a positive combined effect on hyperuricemia. The mutual verification of two outcomes using the three different models provided strong public health implications for protecting people from heavy metal pollution and preventing hyperuricemia.

Demographics of road injuries and micromobility injuries among China, India, Japan, and the United States population: evidence from an age-period-cohort analysis.

BACKGROUND: Micromobility sharing platforms have involved skyrocketing numbers of users in multiple countries since 2010. However, few studies have examined the overall impact of the growing micromobility market on road injuries. METHOD: We use road injury data from the Global Burden of Disease Study database to examine the effect of age, period, and cohort on micromobility injury-related deaths and incidence. We compared four countries that vary in demographic background and road infrastructure. By comparing the countries, we analyzed the relationship between the trends in road injuries and these factors. RESULTS: We found an overall upward trend in micromobility injuries. A higher risk of micromobility-related injuries was witnessed in China and the US in 2015-2019, and people older than 45 showed a growing micromobility-related mortality and incidence rate in China, India, and the US. Cohorts after 1960 showed higher micromobility injury incidence risks in China and India, but the population born after 1990 in India showed a slightly lower risk compared to those before it. CONCLUSIONS: The boosted usage of micromobility devices explains these increasing trends. Road infrastructure and separated traffic ease the collisions from micromobility devices. The overall situation calls for improvement in legislation as well as road infrastructure.

Time Trends in Stroke and Subtypes Mortality Attributable to Household Air Pollution in Chinese and Indian Adults: An Age-Period-Cohort Analysis Using the Global Burden of Disease Study 2019.

Household air pollution (HAP) exposure is recognized as a major health concern in areas relied on residential burning of solid fuels for cooking and heating. However, previous study has focused on mortality across time and reported changes in age-specific mortality globally but failed to distinguish cohort from period effects. Therefore, this study aimed to differentiate the relative contributions of period and cohort effects to overall time trends of HAP-attributable stroke mortality between the most presentative East and South Asia countries. Data were obtained from the Global Burden of Disease (GBD) database. The age, period, and cohort effects were estimated using the age-period-cohort (APC) model. The overall age-standardized mortality rates (ASMRs) of stroke in China decreased by 39.8% compared with 35.8% in India, while stroke subtypes in both the sexes and countries showed consecutive significant declines from 1990 to 2019. The age-specific and cohort-specific HAP-attributable stroke mortality declined over time in China and India. By APC analysis, substantially increasing age effects were presented for stroke and subtypes from 25 to 84 years. China had a rapid reduction in the independent period and cohort effects. Also, the risk of death for subarachnoid hemorrhage (SAH) had the most striking decline for both sexes in period and cohort effects. Reductions of India were less favorable than China, but the independent period and cohort effects progressively decreased during the entire period for both the sexes. Males experienced a slightly higher mortality risk than females in both countries. Although prominent reductions were observed in HAP-attributable stroke and subtypes mortality during the past 30 years, China and India still suffered uneven HAP-attributable stroke burden. Thus, it is of high significance to introduce advanced solid fuels replace technology and knowledge regarding clean fuel use.

Age-Period-Cohort Analysis of Long Trend of Mortality for Stroke and Subtypes Attributed to High SBP in Chinese Adults.

Stroke has been found as the leading cause of death in China, and high systolic blood pressure (SBP) has been indicated as a critical risk factor of stroke mortality. Accordingly, in this article, the aims were to investigate the long-term trends of mortality in terms of stroke and subtypes arising from high SBP stratified by age and gender among Chinese adults. The data of this article originated from the global burden of disease (GBD) study database. The age, period, and cohort effects were examined with the age-period-cohort model (APC). The age-standardized mortality of stroke attributed to high SBP in China has been significantly declining from 1990 to 2019. As indicated by the result of APC analysis, substantially rising age effects have been exerted on stroke and subtypes from 25 to 84 years of both genders, whereas the age effect on women increased less rapidly than that on men. As opposed to the above result, the period and cohort effects were reported to show similar monotonous decrease trends, and stroke of women more significantly declined than that of men (significantly with p < 0.05 for all). All types of stroke mortality arising from high SBP were indicated to change. The risk of death was identified to be most remarkably reduced in high SBP-attributable subarachnoid hemorrhage (SAH), whereas intracerebral hemorrhage (ICH) and ischemic stroke (IS) decreased at approximately the same rate. People born in the later birth cohorts or living in recent periods had a lower risk of stroke death, whereas men and elder groups were considered as the high-risk populations for stroke mortality due to high SBP. Although the stroke mortality relating to high SBP in China was declining, ICH and IS would continue to be the first and second lethal subtypes of stroke. In contrast to the above finding, SAH accounted for the minimum proportion of deaths and the maximum reduction in period and cohort effects. Thus, it is of high significance to introduce advanced hypertension control technology and knowledge regarding healthy lifestyles.

Bi2O2Se-Based True Random Number Generator for Security Applications.

The fast development of the Internet of things (IoT) promises to deliver convenience to human life. However, a huge amount of the data is constantly generated, transmitted, processed, and stored, posing significant security challenges. The currently available security protocols and encryption techniques are mostly based on software algorithms and pseudorandom number generators that are vulnerable to attacks. A true random number generator (TRNG) based on devices using stochastically physical phenomena has been proposed for auditory data encryption and trusted communication. In the current study, a Bi2O2Se-based memristive TRNG is demonstrated for security applications. Compared with traditional metal-insulator-metal based memristors, or other two-dimensional material-based memristors, the Bi2O2Se layer as electrode with non-van der Waals interface, high carrier mobility, air stability, extreme low thermal conductivity, as well as vertical surface resistive switching shows intrinsic stochasticity and complexity in a memristive true analogue/digital random number generation. Moreover, those analogue/digital random number generation processes are proved to be resilient for machine learning prediction.

Investigation on Transparent, Conductive ZnO:Al Films Deposited by Atomic Layer Deposition Process.

Transparent electrodes are a core component for transparent electron devices, photoelectric devices, and advanced displays. In this work, we fabricate fully-transparent, highly-conductive Al-doped ZnO (AZO) films using an atomic layer deposition (ALD) system method of repeatedly stacking ZnO and Al2O3 layers. The influences of Al cycle ratio (0, 2, 3, and 4%) on optical property, conductivity, crystallinity, surface morphology, and material components of the AZO films are examined, and current conduction mechanisms of the AZO films are analyzed. We found that Al doping increases electron concentration and optical bandgap width, allowing the AZO films to excellently combine low resistivity with high transmittance. Besides, Al doping induces preferred-growth-orientation transition from (002) to (100), which improves surface property and enhances current conduction across the AZO films. Interestingly, the AZO films with an Al cycle ratio of 3% show preferable film properties. Transparent ZnO thin film transistors (TFTs) with AZO electrodes are fabricated, and the ZnO TFTs exhibit superior transparency and high performance. This work accelerates the practical application of the ALD process in fabricating transparent electrodes.

What matters: non-pharmaceutical interventions for COVID-19 in Europe.

OBJECTIVES: The purpose of this study is to describe the situation of COVID-19 in European countries and to identify important factors related to prevention and control. METHODS: We obtained data from World Health Statistics 2020 and the Institute for Health Metrics and Evaluation (IHME). We calculated the Rt values of 51 countries in Europe under different prevention and control measures. We used lasso regression to screen factors associated with morbidity and mortality. For the selected variables, we used quantile regression to analyse the relevant influencing factors in countries with different levels of morbidity or mortality. RESULTS: The government has a great influence on the change in Rt value through prevention and control measures. The most important factors for personal and group prevention and control are the mobility index, testing, the closure of educational facilities, restrictions on large-scale gatherings, and commercial restrictions. The number of ICU beds and doctors in medical resources are also key factors. Basic sanitation facilities, such as the proportion of safe drinking water, also have an impact on the COVID-19 epidemic. CONCLUSIONS: We described the current status of COVID-19 in European countries. Our findings demonstrated key factors in individual and group prevention measures.

Secular trends in chronic respiratory diseases mortality in Brazil, Russia, China, and South Africa: a comparative study across main BRICS countries from 1990 to 2019.

BACKGROUND: As the emerging economies, the BRICS (Brazil, Russia, India, China, and South Africa) shared 61.58% of the global chronic respiratory diseases (CRD) deaths in 2017. This study aimed to assess the secular trends in CRD mortality and explore the effects of age, period, and cohort across main BRICS countries. METHODS: Data were obtained from the Global Burden of Disease Study (GBD) 2019 and analyzed using the age-period-cohort (APC) model to estimate period and cohort effects between 1990 and 2019. The net drifts, local drifts, longitudinal age curves, period/cohort rate ratios (RRs) were obtained through the APC model. RESULTS: In 2019, the CRD deaths across the BRICS were 2.39 (95%UI 1.95 to 2.84) million, accounting for 60.07% of global CRD deaths. Chronic obstructive pulmonary disease (COPD) and asthma remained the leading causes of CRD deaths. The age-standardized mortality rates (ASMR) have declined across the BRICS since 1990, with the most apparent decline in China. Meanwhile, the downward trends in CRD death counts were observed in China and Russia. The overall net drifts per year were obvious in China (-5.89%; -6.06% to -5.71%), and the local drift values were all below zero in all age groups for both sexes. The age effect of CRD presented increase with age, and the period and cohort RRs were following downward trends over time across countries. Similar trends were observed in COPD and asthma. The improvement of CRD mortality was the most obvious in China, especially in period and cohort effects. While South Africa showed the most rapid increase with age across all CRD categories, and the period and cohort effects were flat. CONCLUSIONS: BRICS accounted for a large proportion of CRD deaths, with China and India alone contributing more than half of the global CRD deaths. However, the declines in ASMR and improvements of period and cohort effects have been observed in both sexes and all age groups across main BRICS countries. China stands out for its remarkable reduction in CRD mortality and its experience may help reduce the burden of CRD in developing countries.

Effect of pupil matching of cold shield on the fringe contrast of long-wave infrared spatial heterodyne spectroscopy.

Matching the cold shield with the exit pupil of the fringe-imaging system of long-wave infrared (LWIR) spatial heterodyne spectroscopy (SHS) damages illumination uniformity of the interferogram and affects the fringe contrast, which is a significant parameter for LWIR SHS. The optical models of the fringe-imaging system considering and not considering the pupil matching of the cold shield are built to illustrate the effect on the fringe contrast. Simulations based on the optical design software ASAP are conducted to verify the fringe contrast loss for field-widened LWIR SHS. The result shows that the pupil matching of the cold shield decreases the fringe contrast of LWIR SHS and field-widened LWIR SHS by 0.049% and 0.053%, respectively, and the fringe contrast loss increases with the degree of deviation from the telecentric condition of the fringe-imaging system.

The effects of Methanococcus maripaludis on the corrosion behavior of EH40 steel in seawater.

The corrosion behavior of EH40 steel in seawater enriched with Methanococcus maripaludis was investigated through electrochemical methods and surface analysis techniques. The results revealed that the hydrogenotrophic M. maripaludis strain can utilize acetate as an alternative energy source. Corrosion of EH40 steel is initially inhibited, but prolonged exposure with the methanogen leads to an eventual corrosion propagation. During the early stage of immersion in M. maripaludis culture medium, the formation of a protective corrosion products film inhibits EH40 steel corrosion. The presence of M. maripaludis promotes both anodic and cathodic reactions of EH40 steel in the late stage of exposure. Surface analyses revealed that pitting corrosion is closely related to uneven distribution of M. maripaludis biofilm on EH40 steel surface.

Bi2O2Se-Based Memristor-Aided Logic.

The implementation of two-dimensional materials into memristor architectures has recently been a new research focus by taking advantage of their atomic thickness, unique lattice, and physical and electronic properties. Among the van der Waals family, Bi2O2Se is an emerging ternary two-dimensional layered material with ambient stability, suitable band structure, and high conductivity that exhibits high potential for use in electronic applications. In this work, we propose and experimentally demonstrate a Bi2O2Se-based memristor-aided logic. By carefully tuning the electric field polarity of Bi2O2Se through a Pd contact, a reconfigurable NAND gate with zero static power consumption is realized. To provide more knowledge on NAND operation, a kinetic Monte Carlo simulation is carried out. Because the NAND gate is a universal logic gate, cascading additional NAND gates can exhibit versatile logic functions. Therefore, the proposed Bi2O2Se-based MAGIC can be a promising building block for developing next-generation in-memory logic computers with multiple functions.

Higher HEI-2015 Score Is Associated with Reduced Risk of Depression: Result from NHANES 2005-2016.

Globally, the total estimated number of people living with depression increased by 18.4% between 2005 and 2015, with the prevalence being 4.8% in 2015. Many nutrient and diet patterns are proven to be correlated to depression, so we conducted this analysis to explore whether the Healthy Eating Index 2015 (HEI-2015) score is associated with depression, and possibly to provide dietary measures to reduce the risk of depression. Data came from the National Health and Nutrition Examination Survey (2005-2016), a cross-sectional and nationally representative database. The analytic sample was limited to adults: (1) age ≥20 with complete information of HEI-2015 and depression; (2) no missing data of demographics, BMI, drinking, smoking, and fasting plasma glucose. HEI-2015 was calculated using the Dietary Interview: Total Nutrient Intakes, First Day data file. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Weighted logistic regression models were used to explore the relationship between the HEI-2015 score and depression. The final study sample included 10,349 adults, with 51.4% of them being men, representing a population of about 167.8 million non-institutionalized U.S. adults. After multivariable adjustment, average HEI status (OR: 0.848, 95% CI: 0.846-0.849) and optimal HEI status (OR: 0.455, 95% CI: 0.453-0.456) were associated with reduced odds of depression. Poor diet quality is significantly associated with elevated depressive symptoms in U.S. adults. Aligning with the Dietary Guidelines for Americans reduces the risk of depression.

A water-stable zinc(ii)-organic framework as a multiresponsive luminescent sensor for toxic heavy metal cations, oxyanions and organochlorine pesticides in aqueous solution.

A novel metal-organic framework with the formula [Zn3(DDB)(DPE)]·H2O (1) (H5DDB = 3,5-di(2',4'-dicarboxylphenyl)benzoic acid and DPE = 1,2-di(4-pyridyl)ethylene) has been solvothermally synthesized by employing a rigid carboxylate ligand H5DDB to assemble with Zn(ii) ions in the presence of a flexible bis(pyridyl) linker DPE. The Zn-MOF is a 3D framework with six-nuclear clusters and possesses remarkable water stability and pH stability. Interestingly, complex 1 can sensitively and selectively sense Fe(iii), Cr(iii), Cr(vi), Mn(vii) and the pesticide 2,6-Dich-4-NA with low detection limits in aqueous solution. Moreover, complex 1 also exhibits selectivity for 2,6-Dich-4-NA detection in real samples including carrot, grape and nectarine extracts, and its detection ability is almost unchanged in the presence of the surfactant sodium dodecyl sulfate (SDS). The possible mechanisms of luminescence quenching have been explained by the weak affinity of nitrogen atoms, resonance energy transfer, and photoinduced electron transfer. To our knowledge, this is the first example of a MOF-based multiresponsive fluorescent probe for the simultaneous detection of Fe(iii), Cr(iii/vi), Mn(vii) and the pesticide 2,6-Dich-4-NA in aqueous solution.

Two novel metal-organic frameworks based on pyridyl-imidazole-carboxyl multifunctional ligand: selective CO2 capture and multiresponsive luminescence sensor.

Two novel metal-organic frameworks, formulated as [Mn(CIP-)2] (1) and [Ag(CIP-)] (2) (HCIP = 4-(4-carboxylphenyl)-2,6-di(4-imidazol-1-yl)phenyl)pyridine), were solvothermally synthesized based on a pyridyl-imidazole-carboxyl multifunctional ligand. The single-crystal X-ray diffraction analysis shows that complex 1 is a 3D microporous framework with uncoordinated imidazole groups, and complex 2 is a 2D + 2D → 2D 3-fold parallel interpenetrated network. Complex 1 exhibited excellent CO2 selective absorption over N2 and CH4. IAST calculations revealed that the selectivities of 1 for the CO2/CH4 (50 : 50) and CO2/N2 (15 : 85) mixtures were 8.0 and 117 at 273 K under 1 bar, respectively. Moreover, the luminescence investigations displayed that complex 2 is an excellent MOF-based multiresponsive fluorescent probe for Fe3+, CrO42-/Cr2O72- and the pesticide 2,6-Dich-4-nitroaniline, with high selectivity and sensitivity. Notably, complex 2 exhibited a highly sensitive sensing ability (5.2 × 104 M-1) and a low detection limit (1.7 × 10-7 M) for 2,6-Dich-4-nitroaniline. To the best of our knowledge, this is the first Ag-MOF-based fluorescent sensor that can simultaneously detect metal ions, inorganic anions and pesticides.