Rapid assessment of soil accessible Cr(â ¥) in the field by a portable RGB color sensor.

Field rapid determination of soil accessible Cr(Ⅵ) is of great significance for on-site assessment and decision-making about the health risks of contaminated sites. When the thickness of solutions with various concentrations of Cr(Ⅵ) is constant, there would be a quantitative relationship between the chromogenic difference of Cr(Ⅵ) solutions and the concentration of Cr(Ⅵ). The chromogenic difference could be described by Red (R), Green (G), Blue (B) values. Based on the chromogenic reaction between 1,5-diphenylcarbazide and Cr(Ⅵ), this study first established the calibration curve between the chromogenic difference and the concentration of Cr(Ⅵ) in standard solution with or without 0.01 M CaCl2, using an RGB color sensor. This is the subsequent determination basis of the method for rapidly assessing accessible Cr(Ⅵ) in the field (M-RGB). Then, the concentration of accessible Cr(Ⅵ) of contaminated soil with "hand-shaking + standing" field extraction method was compared with "end-over-end shaking" laboratory extraction method. Finally, the accessible Cr(Ⅵ) of contaminated soil extractants was determined via M-RGB integrating the field extraction method. Results indicated there was a highly significant linear relationship between colorimetric difference value (∆E) and Cr(Ⅵ) concentration in the range of 0.1-3 mg/L (R2 > 0.99, P < 0.01), based on the Euclidean formula for calculating ∆E. The "hand-shaking + standing" field extraction method was effective in obtaining accessible Cr(Ⅵ) extractants with or without 0.01 M CaCl2, with the high extraction efficiency within 100±1%. The concentrations of accessible Cr(Ⅵ) in various polluted soils determined by M-RGB were consistent with that determined by the ultraviolet-visible spectrophotometry, with the relative error within ±5%, and the relative standard deviation ≤ 20%. The spiked recovery experiments showed that the recovery of M-RGB was between 95% and 105%, which means M-RGB could realize the trace analysis for accessible Cr(Ⅵ) in the field.

Using an inexpensive RGB color sensor for field quantitative assessment of soil accessible Cu(â ¡).

Field rapid determination of soil accessible Cu(Ⅱ) was important for environmental safety and human health risk assessment. In this study, an inexpensive red, green, and blue (RGB) color sensor was used for quantitative color difference analysis of the colored solution for soil accessible Cu(Ⅱ) with bis-cyclohexanone oxalydihydrazone as color reagent to develop a new method for analyzing soil accessible under field conditions. First, the calibration curve for RGB color sensor method was established in the standard solutions of Cu(II). Then the "hand shaking + standing" field extraction method for accessible Cu(Ⅱ) was developed. Finally, the method was applied in contaminated soils in the laboratory and in the field, and set the values determined by atomic absorption spectroscopy (AAS) as the standard ones. Results indicated that in the range of 0.1-5 mg L-1 Cu(II), the RGB Euclidean chromogenic difference values were directly linear correlated with the concentration of Cu(II) (R2 > 0.999). The interference of Fe(Ⅲ) and Mn(Ⅱ) could be eliminated by adding citric acid. The "hand shaking + standing" field extraction method could effectively extract the accessible Cu(Ⅱ) from soil with the high extraction rates. The concentrations of accessible Cu(II) in various polluted soils determined by RGB color sensor method were consistent with that determined by AAS, with the relative error within ±5%, the relative standard deviation ≤ 20%. The recovery of Cu(II) in RGB color sensor method was between 97% and 105%, which could meet the requirements of trace analysis of accessible Cu(Ⅱ) in the field. The high accuracy and precision of RGB color sensor method was reconfirmed in the rapid field quantitative assessment of soil accessible Cu(Ⅱ). Due to that the RGB color sensor was low cost, rechargeable, portable, mobile, ambient light resistant, the method would have a great potential for the determination of accessible Cu(Ⅱ) in contaminated soils.

Spatial Disparity of Meteorological Impacts on Carbon Monoxide Pollution in China during the COVID-19 Lockdown Period.

Lockdown due to the novel coronavirus disease 2019 (COVID-19) pandemic offers a unique opportunity to study the factors governing the variation in air pollution. A number of studies have investigated the cause underlying the occurrence of heavy haze pollution around the world during the lockdown period. However, information about spatiotemporal variations in gaseous pollutants and detailed quantifications of potential meteorological (METRO) impacts are limited. Ground measurements show that carbon monoxide (CO) pollution deteriorated in northern China despite strict control of human and industrial activities during the lockdown period in early 2020. In this study, a four-dimensional decomposition model was used to quantitatively extract the METRO impacts on the CO pollution over China. The results show that weakened winds elevated CO concentrations near Beijing and in northeastern China. Increased temperatures slightly elevated CO concentrations in northern and eastern China but reduced CO concentrations in northwestern China. Remarkable amounts of CO increases in northern China (e.g., by 0.21 mg/m3 within Beijing) were explained by anomalously high humidity, which could be associated with an enhanced interaction between aerosol and the boundary layer. After excluding the METRO impacts, the CO concentrations drastically declined across China (e.g., by 0.22 mg/m3 within Beijing), indicating that the lockdown indeed greatly lessened CO concentrations. However, the adverse METRO conditions counteracted the beneficial outcomes of emission reductions, leading to a deterioration of the CO pollution in northern China. These results indicate that the METRO factors can play a critical role in worsening air pollution despite a strict control of anthropogenic emissions.

Auditory and Somatosensory P3 Are Complementary for the Assessment of Patients with Disorders of Consciousness.

The evaluation of the level of consciousness in patients with disorders of consciousness (DOC) is primarily based on behavioural assessments. Patients with unresponsive wakefulness syndrome (UWS) do not show any sign of awareness of their environment, while minimally conscious state (MCS) patients show reproducible but fluctuating signs of awareness. Some patients, although with remaining cognitive abilities, are not able to exhibit overt voluntary responses at the bedside and may be misdiagnosed as UWS. Several studies investigated functional neuroimaging and neurophysiology as an additional tool to evaluate the level of consciousness and to detect covert command following in DOC. Most of these studies are based on auditory stimulation, neglecting patients suffering from decreased or absent hearing abilities. In the present study, we aim to assess the response to a P3-based paradigm in 40 patients with DOC and 12 healthy participants using auditory (AEP) and vibrotactile (VTP) stimulation. To this end, an EEG-based brain-computer interface was used at DOC patient's bedside. We compared the significance of the P3 performance (i.e., the interpretation of significance of the evoked P3 response) as obtained by 'direct processing' (i.e., theoretical-based significance threshold) and 'offline processing' (i.e., permutation-based single subject level threshold). We evaluated whether the P3 performances were dependent on clinical variables such as diagnosis (UWS and MCS), aetiology and time since injury. Last we tested the dependency of AEP and VTP performances at the single subject level. Direct processing tends to overestimate P3 performance. We did not find any difference in the presence of a P3 performance according to the level of consciousness (UWS vs. MCS) or the aetiology (traumatic vs. non-traumatic brain injury). The performance achieved at the AEP paradigm was independent from what was achieved at the VTP paradigm, indicating that some patients performed better on the AEP task while others performed better on the VTP task. Our results support the importance of using multimodal approaches in the assessment of DOC patients in order to optimise the evaluation of patient's abilities.

[Ecological Risk Assessment of Heavy Metals at Township Scale in the High Background of Heavy Metals, Southwestern, China].

Heavy metals (HMs) are naturally occurring elements that have high natural background levels in the environment. Therefore, it is important to conduct ecological risk assessment and identify potential sources of HMs. In the past, studies were conducted at the regional scale. The accuracy of those studies could not meet the needs of spatial planning and natural resource management. Therefore, it is necessary to conduct ecological risk assessment at the township scale. In this study, 1092 soil samples (from 0-20 cm depth) were collected in the town of Reshui, an area with high background levels of soil HMs with the parent material of carbonatite, which is commonly found in Southwest China. The town of Reshui is a multi-ecological risk superimposed area where the ecological risk is high. In this study, concentrations of HMs (Cd, Cr, As, Hg, Pb, Cu, Zn, and Ni) in the topsoil were analyzed, and statistical analysis (SA), geographic information system (GIS) modeling, and positive matrix factorization (PMF) analysis were performed. The geoaccumulation index (Igeo) and potential ecological risk index (PERI) were applied for the ecological risk assessment and quantification of the sources of the soil HMs. The mean values of HM concentrations in the topsoil were 18.1, 1.18, 174.1, 202.2, 0.09, 71.1, 34.9, and 167.2 mg ·kg-1for As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, respectively, which were considerably higher than the average background value (ABV) in soils in Yunnan Province except for As and Pb. The average concentrations of Cd, Cr, Cu, and Ni exceeded the screening values specified in the soil contamination risk in agricultural land (GB 15618-2018) by 5.82, 1.16, 4.04, and 1.02 times, respectively. The Igeo value shows that the major pollutant is Cu in the surface soil of the study area, followed by Cr, and Cd. Speciation analysis of HMs indicates that HMs (Cr, As, Pb, Cu, Zn, and Ni) mainly exist in the residual form, mostly from the geological background with low bioavailability. The potential effective components of Hg have higher levels, but the total amount of Hg and its pollution risk are lower. Cd has a high bioavailability ratio, is easy to enter the soil solution and be absorbed by crops, and is the HM with the highest pollution risk in the study area. The PERI shows that the proportions of low ecological risk, moderate risk, and high risk soil samples are 44.23%, 54.40%, and 1.37% of the total number of samples, respectively. Hg and Cd were the major sources of risk because of their high toxicity coefficient. The PMF analysis indicates that there are four major sources of HMs in the study area: human activity, natural sources, coal mining and traffic emissions, and agricultural sources with the risk contribution ratios of 9.29%, 53.67%, 11.23%, and 25.81%, respectively. The PMF analysis effectively quantified the ecological risk from these sources, providing a reference for further pollution control and prevention measures.

Homogeneous BTK Occupancy Assay for Pharmacodynamic Assessment of Tirabrutinib (GS-4059/ONO-4059) Target Engagement.

Bruton's tyrosine kinase (BTK) is a clinically validated target for B-cell leukemias and lymphomas with FDA-approved small-molecule inhibitors ibrutinib and acalabrutinib. Tirabrutinib (GS-4059/ONO-4059, Gilead Sciences, Inc., Foster City, CA) is a second-generation, potent, selective, irreversible BTK inhibitor in clinical development for lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL). An accurate pharmacodynamic assay to assess tirabrutinib target coverage in phase 1/2 clinical studies will inform dose and schedule selection for advanced clinical evaluation. We developed a novel duplex homogeneous BTK occupancy assay based on time-resolved fluorescence resonance energy transfer (TR-FRET) to measure free and total BTK levels in a multiplexed format. The dual-wavelength emission property of terbium-conjugated anti-BTK antibody served as the energy donor for two fluorescent energy acceptors with distinct excitation and emission spectra. The assay was characterized and qualified using full-length purified recombinant human BTK protein and peripheral blood mononuclear cells derived from healthy volunteers and patients with CLL. We demonstrated assay utility using cells derived from lymph node and bone marrow samples from patients with CLL and DLBCL. Our TR-FRET-based BTK occupancy assay provides accurate, quantitative assessment of BTK occupancy in the clinical trial program for tirabrutinib and is in use in ongoing clinical studies.

Functional assessment of CYP3A4 allelic variants on lidocaine metabolism in vitro.

AIM: Human cytochrome P450 3A4 is the most abundant isoform of P450 enzyme in the liver. It plays an important role in the metabolism of wide variety of xenobiotic and endogenous substrates. So far, there are few reports about the functional characterization of CYP3A4 variants in terms of specific substrates. The aim of this study was to systematically investigate the genetic polymorphisms of 23 CYP3A4 alleles and evaluate their catalytic activities on the metabolism of lidocaine in vitro. METHODS AND RESULTS: The wild-type and 22 CYP3A4 variants were expressed in Spodoptera frugiperda 21 insect cells. Then the insect microsomes were incubated with the CYP3A4-specific substrate lidocaine. Reactions were performed with 50-3,000 µM for 60 min at 37°C. Lidocaine and its metabolite monoethylglycinexylidide were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry system. Of the 23 CYP3A4 allelic variants tested, 2 variants (CYP3A4*17 and CYP3A4*30) had no detectable enzyme activity; and 5 variants (CYP3A4*2, CYP3A4*5, CYP3A4*9, CYP3A4*16 and CYP3A4*24) showed significantly decreased intrinsic clearance values compared with wild-type CYP3A4*1. CONCLUSION: As the first study of all these CYP3A4 alleles for lidocaine metabolism, our results in vitro assessment may provide novel insights into the allele-specific and substrate-specific activity of CYP3A4 and may also offer a reference to the personalized treatment of lidocaine in a clinical setting.

Assessment of CYP2B6 activity in rats: a cocktail study with bupropion alone and in combined with tolbutamide.

A "cocktail"of numerous probe drugs to assess the metabolic activity of the corresponding cytochrome P450 enzymes requires that there is no problem of interaction among them. Some interactions among probe drugs can appear and may affect the rate of biotransformation of other ones. To develop a useful "cocktail" of probe drugs, our presented work was aimed on the influence of tolbutamide on cytochrome P450-mediated metabolism of bupropion. The biotransformation rates of bupropion administered either separately or in combined with tolbutamide were compared in this new study. The results revealed that tolbutamide had significantly decreased the rate of bupropion hydroxylation. Thus, due to shift in cytochrome P450 enzyme metabolic activity some extent differential results in the rate of P450-mediated metabolism can be observed when comparing assessment using combination of two model drugs with the common way (single marker use).