From bench to bedside - is there a role of IL-17 drugs in rheumatoid arthritis?

INTRODUCTION: IL-17 has been described as a pro-inflammatory cytokine that is relevant in the seronegative spondylarthritides with IL-17 targeted therapies being licensed for their treatment.There is evidence to demonstrate that IL-17 is found in RA joints and contributes to the pro-inflammatory cascade. This results in synovial hyperplasia and osteoclastogenesis thus causing joint destruction and bony erosions. AREAS COVERED: This review article summarizes trials that have studied the use of IL-17 targeted therapies in RA patients who have failed conventional synthetic disease-modifying therapy (C-DMARDS) and biologic DMARDS. EXPERT OPINION: The trials that have studied IL-17 inhibitors in RA patients have only shown a modest improvement in disease activity. In several trials, the primary endpoint was not achieved whilst in others, when comparing with existing licensed biologics for RA, did not demonstrate any superiority.Tissue Necrosis Factor-alpha (TNF-α) likely plays more of a pivotal role in the pathogenesis of RA with IL-17 having a synergistic effect. Therefore, in our opinion, IL-17 inhibitors as an independent therapy for RA are less likely to provide a cost-effective benefit. There may be scope to potentially combine it with TNF-α-inhibitors (TNF-i), but this requires further research especially with the potential concerns related to increased immunosuppression.

Low-cost BPO4 In Situ Synthetic Li3PO4 Coating and B/P-Doping to Boost 4.8 V Cyclability for Sulfide-Based All-Solid-State Lithium Batteries.

Structural damage of Ni-rich layered oxide cathodes such as LiNi0.8Co0.1Mn0.1O2 (NCM811) and serious interfacial side reactions and physical contact failures with sulfide electrolytes (SEs) are the main obstacles restricting ≥4.6 V high-voltage cyclability of all-solid-state lithium batteries (ASSLBs). To tackle this constraint, here, a modified NCM811 with Li3PO4 coating and B/P co-doping using inexpensive BPO4 as raw materials via the one-step in situ synthesis process is presented. Phosphates have good electrochemical stability and contain the same anion (O2-) and cation (P5+) as in cathode and SEs, respectively, thus Li3PO4 coating precludes interfacial anion exchange, lessening side reactivity. Based on the high bond energy of B─O and P─O, the lattice O and crystal texture of NCM811 can be stabilized by B3+/P5+ co-doping, thereby suppressing microcracks during high-voltage cycling. Therefore, when tested in combination with Li─In anode and Li6PS5Cl solid electrolytes (LPSCl), the modified NCM811 exhibits extraordinary performance, with 200.36 mAh g-1 initial discharge capacity (4.6 V), cycling 2300 cycles with decay rate as low as 0.01% per cycle (1C), and 208.26 mAh g-1 initial discharge capacity (4.8 V), cycling 1986 cycles with 0.02% per cycle decay rate. Simultaneously, it also has remarkable electrochemical abilities at both -20 °C and 60 °C.

A 20-year shift in China's sewage sludge heavy metals and its feasibility of nutrient recovery in land use.

Recycling resources from wastewater is even more important for developing a more sustainable society. Disposing sewage sludge, which accumulates most pollutants and resources in sewage, is the main challenge in wastewater pollution control and resource utilization. Heavy metals (HMs) are the greatest constraint limiting the application of sewage sludge to land as a sustainable use of this material. We conducted a meta-analysis of the concentrations of HMs in Chinese sewage sludge by combining data from studies published from 2000 to 2019 (N = 8477). Over this period, the reported concentrations of HMs in sewage sludge declined in three stages (a fluctuating stage, a slight decrease stage, and a rapid and stable decrease stage). The results revealed that economic development and environmental policy implementation were the main factors mitigating HM pollution in sewage sludge in China. Moreover, if environmental regulations were strengthened and HM pollution-mitigation strategies were made consistent, such that the proportion of sewage sludge applied to land in China could be increased from 18.6% to 48.0% (the proportion applied to land in the United States), the ecosystem services analysis showed that huge ecological-economic benefits could be realized (3.1 billion Chinese Yuan) and the use of fertilizers could be substantially reduced (the use of nitrogen fertilizers by 8.5% and the use of phosphate fertilizers by 18.1%). This review shows that China should formulate a unified policy and interdepartmental committee for sustainable application of sewage sludge to land and wastewater resource recycling management.

[Meteorological Impact Assessment of PM2.5 and O3 Complex Pollution in Key Regions of China Based on Meteorological Conditions Index].

Meteorological conditions play a key role in the occurrence and evolution of atmospheric complex pollution. Considering the different pollution formation mechanisms of PM2.5 and O3, statistical calculation and in-depth learning methods were used to construct the PM2.5 and O3 meteorological condition indexes based on long-term pollution meteorological observation data. A research method was developed to study the meteorological characteristics and impact contribution of atmospheric complex pollution by using the meteorological condition index, and quantitative analysis of the distribution and variation of pollution excluding the influence of regional meteorological differences was also conducted. The results showed that in the summer of 2021, the pollution meteorological conditions in the key regions in central and eastern China were generally worse in the north and better in the south(index:"2+26" cities>the border area of Jiangsu, Anhui, Shandong, and Henan>the Yangtze River Delta) and the worst in June and the best in July. The "double high" pollution began to appear when the PM2.5 meteorological condition index>30 and O3 meteorological condition index>100; meanwhile, the unfavorable meteorological conditions for O3 also promoted the increase in PM2.5 concentration, resulting in the frequency of "double high" increases with the increase in O3 meteorological condition index. Compared with that during the same period last year, ρ(PM2.5) of each region decreased by 3.9 µg·m-3, 3.3 µg·m-3, and 1.4 µg·m-3 due to the contribution of the improvement in the pollution meteorological conditions, which is nearly 58.5% on average of the total decrease in PM2.5 concentration. However, the change in O3 pollution meteorological conditions was better in the north and worse in the south, and the overall deterioration in the Yangtze River Delta Region led to approximately 2.8 µg·m-3 growth for the O3 concentration. The PM2.5 and O3 concentrations after excluding the impact of meteorological differences showed different distribution characteristics from the air quality monitoring, in which the high concentrations of PM2.5 were distributed along the Bohai Sea, the inter-provincial border, and the south of the region, whereas the high concentrations of O3 were concentrated along the Taihang Mountains, around Mount Tai, and in parts of the Yangtze River Delta. The daily concentration variations in a single city during a specific pollution control period could be used as a basis for evaluating the effectiveness of local supervision and control, which will provide a reference for the dynamic supervision and daily scheduling of local control management.

Epidemiology, clinical presentation, pathophysiology, and management of long COVID: an update.

The increasing number of coronavirus disease 2019 (COVID-19) infections have highlighted the long-term consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection called long COVID. Although the concept and definition of long COVID are described differently across countries and institutions, there is general agreement that it affects multiple systems, including the immune, respiratory, cardiovascular, gastrointestinal, neuropsychological, musculoskeletal, and other systems. This review aims to provide a synthesis of published epidemiology, symptoms, and risk factors of long COVID. We also summarize potential pathophysiological mechanisms and biomarkers for precise prevention, early diagnosis, and accurate treatment of long COVID. Furthermore, we suggest evidence-based guidelines for the comprehensive evaluation and management of long COVID, involving treatment, health systems, health finance, public attitudes, and international cooperation, which is proposed to improve the treatment strategies, preventive measures, and public health policy making of long COVID.

Assessment on binding characteristics of ethiprole and a model protein bovine serum albumin (BSA) through various spectroscopic techniques integrated with computer simulation.

To investigate the binding characteristics of pesticide ethiprole (ETP) with serum albumin is of great significance for pathological analysis of pesticide poisoning, gene mutation, and clinical detection. In present work, the binding characteristics of ETP with a model protein BSA has been estimated by means of multi-spectroscopic approaches integrated with computer simulation. The outcomes testified that the intrinsic fluorescence of BSA was mainly quenched by ETP in a static quenching mode and the stable ETP-BSA complex with the stoichiometry of 1:1 and the binding constant of 6.81 × 103 M-1 (298 K) was produced. The outcomes revealed that ETP combined preferentially to the subdomain IIA (Site I) of BSA and caused the decline in the content of α-helix of BSA and the enhancement in the hydrophobicity of environment centered on Trp residues. The outcomes of experimental and theoretical studies provide the sufficient evidence about the driving forces for the complexation of ETP with BSA, which included van der Waals forces (vdW), hydrogen bonding (H-bonding) interaction, and hydrophobicity. Simultaneously, the theoretical calculation results also confirmed the existence of the significant changes in the physicochemical natures of ETP including molecular conformation, dipole moment, frontier orbital energy, and the atomic charge distribution, which was a responsible for the complexation with BSA.Communicated by Ramaswamy H. Sarma.

Comparing the application of three thrombosis risk assessment models in patients with acute poisoning: A cross-sectional survey.

Background: Patients with acute toxic hemoperfusion are prone to deep vein thrombosis. However, there is no risk assessment model for thrombosis in patients with acute toxic hemoperfusion. Therefore, we compared three commonly used risk assessment models for deep vein thrombosis to determine the model most suitable for assessment of deep vein thrombosis in patients with acute toxic hemoperfusion. Methods: Caprini, Autar, and Padua thrombosis risk assessment models were used to assess the risk of deep vein thrombosis in patients with acute poisoning and hemoperfusion admitted to a grade A hospital in Shandong province from October 2017 to February 2019. The predictive values of the three models were compared using receiver operating characteristic (ROC) curve analysis. Results: The risk assessment model scores of Caprini, Autar, and Padua were 7.55 ± 1.76, 8.63 ± 2.36, and 3.92 ± 0.55, respectively. The Caprini risk assessment model was significantly different (p < 0.05) in high-risk patients in the thrombus and non-thrombotic groups; the difference between the other two models was not significant (p > 0.05). The areas under the ROC curve of the Caprini, Autar, and Padua risk assessment models were 0.673, 0.585, and 0.535, respectively. The difference in areas under the ROC curve between the Caprini risk assessment model and the Autar risk assessment model as well as the Padua risk assessment model was significant (p < 0.05), but the areas under the ROC curve of the Autar risk assessment model and the Padua risk assessment model were not statistically significant (p > 0.05). The Caprini risk assessment model had a sensitivity of 91.9%, specificity of 33.1%, and a Youden index of 0.249. The sensitivity and specificity of Autar's risk assessment model were 37.0 and 77.2%, respectively, and the Youden index was 0.141. The Padua risk assessment model had a sensitivity of 91.3%, specificity of 15.0%, and a Youden index of 0.063. Conclusion: The three thrombosis risk assessment models were not suitable for patients with acute poisoning and hemoperfusion.

Assessment of the temporal variability and health risk of atmospheric particle-phase polycyclic aromatic hydrocarbons in a northeastern city in China.

In this study, we examined the sources and temporal variability of 16 polycyclic aromatic hydrocarbons (PAHs) found in fine particulate matter (PM2.5) in a typical industrial city in northern China. We also evaluated the incremental lifetime cancer risk (ILCR) from the inhalation of these PAHs. Atmospheric PM2.5 samples were collected for 7 consecutive days each month from 2014 to 2019, and the 16 PAHs were measured using multiplex gas chromatography-tandem mass spectrometry. The carcinogenic risk of PAH exposure was assessed using the inhalation unit risk (IUR) and cancer slope factor (CSF) methods. The annual average concentrations of PM2.5 for each year from 2014 to 2019 were 102.87±55.25, 86.92±60.43, 69.17±37.74, 58.20±59.15, 56.01±34.52, and 52.54±58.15 µg m-3, and the annual average ΣPAH concentrations were 56.03±81.09, 47.99±79.30, 40.41±57.31, 33.57±51.79, 43.23±74.80, and 25.20±50.91 ng m-3, respectively. Source identification, using diagnostic ratio analysis, indicated that the major PAH sources were coal/biomass combustion, fuel combustion, and traffic emissions. A health risk assessment showed that the ILCR from PAH inhalation decreased throughout the study period and varied with age. The IUR and CSF methods both showed that the adult ILCR exceeded 1.0×10-6. These findings demonstrate the importance of addressing the carcinogenic risk of PM2.5-bound PAHs, particularly in adults.

Social Interaction With Relapsed Partner Facilitates Cocaine Relapse in Rats.

Social factors strongly contribute to drug use and relapse, and epidemiological studies have found that members of peer groups influence each other to use drugs. However, previous animal models mostly failed to incorporate social factors and demonstrate the effects of social partners on drug addiction and relapse. In the present study, we investigated the transfer of relapse to cocaine seeking between drug-addicted partners in rats. Male Sprague-Dawley rats were pair-housed and subjected to training and extinction of cocaine self-administration and conditioned place preference (CPP). 24 h after extinction test, the targeted rats interacted with a cocaine-primed (relapsed) partner or stranger, or saline-injected (unrelapsed) partner for 30 min, after which the targeted rats were tested for drug seeking behavior. We found that social interaction with a relapsed partner increased drug seeking behavior in cocaine self-administration and CPP models in rats, while social interaction with an unrelapsed partner or relapsed stranger had no effect on cocaine seeking. Moreover, the effect of social interaction on cocaine seeking could last for at least 1 day. Our findings demonstrate a facilitation effect of relapsed social partners on drug relapse in rats and provide a novel animal model for social transfer of drug relapse.

Does Industrial Agglomeration or Foreign Direct Investment Matter for Environment Pollution of Public Health? Evidence From China.

This article focuses on the interaction between China's industrial agglomeration, foreign direct investment (FDI) and environmental pollution of public health in the past 15 years. By conducting theoretical and empirical research, we try to reveal the relationship and mechanism between the economic growth and public health from the perspective of environmental pollution. By constructing an embedded theoretical model of industrial agglomeration and FDI, this article combines other environmental pollution influencing factors, expounds the impact mechanism of industrial agglomeration on environmental pollution. Based on the provincial-level panel data of China on environmental pollution and industrial agglomeration, the empirical test is carried out through the threshold panel regression model. According to the results, industrial agglomeration can significantly rectify the regional environmental pollution, thereby benefiting public health. FDI has a phased impact on the relationship between industrial agglomeration and environmental pollution. Specifically, when the level of FDI is low, the positive improvement effect of industrial agglomeration on environmental pollution is relatively strong. This is mainly because industrial agglomeration can promote economic growth, technological progress, and enhance environmental awareness. When the level of FDI exceeds the first threshold and continues to rise, the positive improvement effect of industrial agglomeration is maximized. Before the level of FDI exceeds the second threshold, this effect gradually weakens. The population concentration and excessive expansion of city scale brought about by industrial agglomeration will lead to the increase of regional resource and energy consumption, thus aggravating environmental pollution. The policy implication is that while the government and enterprises are vigorously increasing the level of foreign investment, they must pay equal attention to economic growth and public health, and the level of industrial agglomeration should match the level of foreign investment so as to give full play to the positive improvement effect of industrial agglomeration on environmental pollution, and realize the coordinated development of the regional economy, environment and population health.

[Levels and Risk Assessment of Short and Medium-Chain Chlorinated Paraffins in Soil from Paper Mill Area].

Short-chain chlorinated paraffins are persistent organic pollutants, and chlorinated paraffins were widely used as sizing agent in the paper industry. In order to investigate the levels and risk assessment of short-chain and medium-chain chlorinated paraffins in the paper mill plant, the surface soil and soil of different depths were collected.The concentrations, congener group profiles of short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) in soil were determined by two-dimensional gas chromatography coupled with electron capture-negative ion mass spectrometry. The SCCPs and MCCPs concentrations were 42-3853 ng·g-1 and 34-2091 ng·g-1. The chlorine contents were 59.9%-61.9% and 48.7%-52.8%. The concentrations of SCCPs and MCCPs were different in the soil collected in different sampling site. The concentration of SCCPs and MCCPs were relatively higher in soil of sewage treatment area and coating area. The CP levels in soil from the paper mill plant were at a high level compared with those in other regions. C10Cl6-7 and C14-15Cl5 were the main congener groups in most soil samples. The results of principal component analysis showed that the CP52 commercial products may be sources of SCCPs and MCCPs in the soil. The risk quotient (RQ) for SCCPs and MCCPs were assessed in soil of paper mill plant. The results showed that the RQ values for SCCPs in soil ranged from 0.01 to 0.73 which are the medium risk, and the RQ values for MCCPs in soil ranged from 0 to 0.07, which are the low risk. The human exposure values of children and adults are lower than TDI[10 µg·(kg·d)-1] in both cases. The health risks caused by non-dietary exposure under paper mill area are low.

[Quantitative Assessment of Human Health Risks Based on Soil Heavy Metals and PAHs Sources:Take a Polluted Industrial Site of Beijing As an Example].

In this study, 130 surface soil samples were collected at an industrial pollution site in Beijing and the contents of As, Be, Cd, Cu, Cr, Hg, Ni, Pb, Sb, Ti, Zn, and 16 PAHs were determined. The positive matrix factorization (PMF) model was used to analyze the sources of heavy metals and PAHs, and the contributions of these sources to carcinogenic risk and hazard index in the study area were calculated. The results showed that the contents of Cd, Cu, Pb, Hg, As, Zn, and Cr in the soil exceeded the background values in different degrees; Cd, Hg, Pb, Zn, and Cu exceeded the background values by>50%. Low molecular weight PAHs (two and three rings) and high molecular weight PAHs (four to six rings) accounted for 39.6% and 60.4% of the total content of 16 PAHs. The PAH content at 77% of the sampling points at the target site was more than 1000 µg ·kg-1, which suggests severe PAH pollution at the site. Heavy metals Be, Ti, As, and Ni mainly originated from natural sources. There are three major sources of 7 heavy metals and 16 PAHs at the site: coal combustion (Hg and ∑16PAHs), smelting (Cu, Cr, Pb, and Zn), and traffic (Sb and Cd). The contribution rates of these sources to the total average contents of seven heavy metals and sixteen PAHs at 130 sampling sites were 8.46% (coal combustion), 90.61% (smelting), and 0.94% (traffic). Human health risk assessment results showed that the carcinogenic risk of seven heavy metals and ∑16PAHs ranged from 4.17×10-6 to 39.38×10-4, and the hazard index ranged from 0 to 32.23. The maximum carcinogenic risk and hazard index values were calculated near the coking plant. Benzo[α]pyrene was the PAH that posed the highest carcinogenic risk and Zn was the heavy metal that had the highest hazard index value. The average carcinogenic risk of coal combustion was 2.16×10-4, accounting for 50.26% of the total average carcinogenic risk. The average hazard index of smelting was 0.834, accounting for 56.43% of the total average non-carcinogenic risk. These two pollution sources are responsible for the high levels of heavy metals and PAHs in the soil of the steel smelting sites that pose the most severe health risks. The results of this study can provide reference for soil remediation and process optimization at other heavily polluted industrial sites.

Assessment on the binding affinity between ritonavir with model transport protein: a combined multi-spectroscopic approaches with computer simulation.

The binding affinity between ritonavir (RTV) and model transport protein, BSA was assessed through multi-spectroscopic approaches and computer simulation. The findings revealed RTV statically quenched the fluorescence of BSA and formed the 1:1 RTV-BSA complex with the binding constant (Kb) of 1.06 × 103 ∼ 5.08 × 103 M-1 under the studied temperatures (298 ∼ 310 K). During the interaction of RTV with BSA, the hydrogen bonds and van der Waals forces acted as predominant function while the hydrophobicity played an assistant function. Molecular modeling further verified the result obtained from the competitive binding experiments, RTV preferentially fit into in the sub-domain IIIA of BSA. The perturbation in the secondary structures of BSA upon acting with RTV was observed from IR results, whereas synchronous and 3D fluorescence spectral findings unraveled the slight change in the hydrophobicity surrounding Tyr and Trp residues.Communicated by Ramaswamy H. Sarma.

Assessment on the binding characteristics of dasatinib, a tyrosine kinase inhibitor to calf thymus DNA: insights from multi-spectroscopic methodologies and molecular docking as well as DFT calculation.

The binding characteristics of calf thymus DNA (ct-DNA) with dasatinib (DSTN), a tyrosine kinase inhibitor was assessed through multi-spectroscopic methodologies and viscosity measurement combined with molecular docking as well as DFT calculation to understand the binding mechanism, affinity of DSTN onto ct-DNA, effect of DSTN on ct-DNA conformation, and among others. The results confirmed DSTN bound onto ct-DNA, leading to forming the DSTN-ct-DNA complex with the binding constant of 4.82 × 103 M-1 at 310 K. DSTN preferentially inserted to the minor groove of ct-DNA with rich A-T region, that was the binding mode of DSTN onto ct-DNA was groove binding. The enthalpic change (ΔH0) and entropic change (ΔS0) during the binding process of DSTN with ct-DNA were 128.9 kJ mol-1 and 489.2 J mol-1 K-1, respectively, confirming clearly that the association of DSTN with ct-DNA was an endothermic process and the dominative driven-force was hydrophobic interaction. Meanwhile, the results also indicated that there was a certain extent of electrostatic force and hydrogen bonding, but they maybe play an auxiliary role. The CD measurement results confirmed the alteration in the helical configuration of ct-DNA but almost no change in the base stacking after binding DSTN. The results revealed that there was the obvious change in the conformation, the dipole moment, and the atomic charge distribution of DSTN in the B-DNA complexes, compared with free DSTN, to satisfy the conformational adaptation. From the obtained fronitier molecular orbitals of DSTN, it can be inferred that the nature of DSTN alters with the change of the environment around DSTN. Communicated by Ramaswamy H. Sarma.

[Heavy Metal Pollution Characteristics and Ecological and Health Risk Assessment of Atmospheric PM2.5 in a Living Area of Zhengzhou City].

To study the pollution characteristics of atmospheric heavy metal elements in a living area of Zhengzhou City, assess the potential ecological risks, and determine risks to resident health in this city, the Wuhan Tianhong TH-16A Airborne Particles Intelligent Sampler was used to collect atmospheric PM2.5 in Zhengzhou City. The mass concentrations of 17 metal elements were analyzed by ambient air determination of inorganic elements by ambient particle matter wavelength dispersive X-ray fluorescence spectrometry. The source of heavy metals was analyzed by the enrichment factor method and principal component analysis. The ecological risk index method and the US Environmental Protection Agency's health risk assessment method were used to evaluate the potential ecological risks and residents' health risks from Cr, Cd, Cu, Zn, Ni, Pb, As, and other elements. The results showed that metals with higher enrichment factor values were Cd, Sb, Pb, and As, and Cd had the highest enrichment factor value. The sources of metal elements in a living area of Zhengzhou City were mainly crust/burning coal, fuel, garbage burning, metallurgical dust, and vehicle emission. The single factor potential ecological hazard index values of Cd, Pb, Zn, As, Cu, Ni, and Cr were 70420.2, 255.3, 204.6, 71.5, 36.9, 24.0, and 5.1, respectively. Cd, As, and Cr in a living area of Zhengzhou City posed a cancer risk, and Cd was the most harmful. Mn had a non-carcinogenic risk.

[Emission Characteristics Analysis and Health Risk Assessment of Unorganized VOCs in the Carbon Industry, Zhengzhou].

The three typical carbon enterprises in Zhengzhou were selected as research targets, and the emission characteristics of volatile organic compounds (VOCs) and their ozone formation potential (OFP) in different functional areas were studied. The US Environmental Protection Agency (EPA) health risk assessment model was used to evaluate the health risks of VOCs emitted by the carbon industry. The results showed that the concentration of VOCs in the production areas of the three research enterprises was between 89.77-964.60 µg·m-3, and the management area was between 51.46-121.59 µg·m-3. Naphthalene and carbon disulfide were at the highest concentrations in the carbon plants. The ozone formation potential of VOCs in the production area was between 75.42-1416.73 µg·m-3, and in the management area was between 65.32-202.42 µg·m-3, mainly from the contribution of aromatic hydrocarbons and olefins. The carcinogenic health risk (Risk) of VOCs in the production area was 3.5×10-5-2.8×10-3, and in the management area was 2.0×10-5-9.4×10-5, which was higher than the maximum acceptable level recommended by the EPA (10-6). The non-carcinogenic health risk index (HI) of the VOCs in the production area was 3.2-1.4×102, and in the management area was 4.3×10-1-3.8, except for the management area of the first enterprise, which was greater than 1, which may expose the workers. These health factors cause cancer and non-carcinogenic hazards.

[Spatial Distribution and Pollution Assessment of As at a Small Scale in Agricultural Soils of the Karst Region].

The karst landforms in Guizhou are widely distributed, and the problem of soil arsenic (As) pollution is prominent in these areas because of the high environmental background levels. In order to study the distribution characteristics of As contents in agricultural soils with high background values of As, representative As polluted regions (typical karst region, semi-karst region) in southwestern Xingyi City of Guizhou Province were selected as the research objects, and the non-karst region served as the control group. Geostatistical analyses were then combined with GIS data to study the spatial variability and pollution conditions of As in agricultural soils. Furthermore, Moran's I statistic was used to analyze the spatial autocorrelation and directional characteristics of As at a small scale in the soil. The results showed that As contents in soils from different geomorphological regions were ranked as follows:typical karst region > semi-karst region > non-karst region. The arithmetic mean value and geometric mean value of As in agricultural soils in the typical karst region were 47.9 mg·kg-1 and 43.3 mg·kg-1, respectively. Meanwhile, the arithmetic mean value and geometric mean value of As in agricultural soils in the semi-karst region were 36.8 mg·kg-1 and 30.1 mg·kg-1, respectively. The As content in agricultural soils from these two regions was significantly higher than the background values of As in Guizhou. In addition, the standard exceedance rates of As in those two regions were 98.5% and 96.7%, respectively, thus demonstrating a high degree of As accumulation. In contrast, the standard exceedance rate of As in the non-karst region was only 6.7%. Among these three afore-mentioned landform types, the results of independent sample T tests showed that there were no significant differences in the content of As between agricultural soil and (natural) soil (P>0.05). The Moran's I coefficient of the As content in agricultural soil was 0.45, and the Z value was 11.61, thus suggesting that there was a significant positive spatial autocorrelation at the small scale (P<0.05), especially in the northeast-southwest direction, and the structural variation was dominant. The As polluted agricultural soils were generally at the slight pollution and mild pollution levels, which accounted for 27.10% and 29.02% of the samples, respectively. However, some regions were at the level of moderate pollution. The non-polluted samples accounted for 41.94% of the samples.

[Cd Accumulation and Risk Assessment for Arable Soils in the Karst Region of Northern Luodian, Guizhou].

Background levels of cadmium (Cd) in carbonate rock areas of Guizhou Province are high. In order to understand the characteristics of Cd in arable soils in these karst areas, the soils in the northern county of Luodian were selected as the study object. By comparing soils in non-karst areas, the distribution characteristics of soil Cd were studied by combining geostatistical analysis and GIS, and the potential ecological risk index and health risk were used to evaluate the potential level of risk to adults and children. The results show that the arable soil Cd content in this karst area is significantly higher than that in non-karst areas (P<0.05), with a geometric mean of 1.33mg·kg-1 and 0.27 mg·kg-1, respectively. In comparison, the geometric mean of soil Cd content in forested land in the same areas is 1.57mg·kg-1 and 0.22 mg·kg-1, respectively. Based on "soil pollution risk control standards", the Cd content of 90% and 22% of arable soil samples was higher than the risk screening value and the risk control value for karst and non-karst areas, respectively. The areas with medium and high Cd values were mainly distributed in the karst areas, presenting medium to strong ecological risks and extremely strong ecological risks, respectively. In contrast, the areas with the lowest Cd concentrations were distributed in the non-karst areas of Jiaoyan, presenting low potential ecological risk. The health risk assessment showed that the non-carcinogenic risk and carcinogenic risk of the three exposure pathways for adults and children in the karst areas are significantly higher than those in the non-karst areas, but the Cd content in the soil does not present non-carcinogenic and carcinogenic risks to local residents. Overall, the problem of Cd pollution in arable soils in the karst area of northern Luodian, Guizhou, is prominent. Therefore, the study of the risks posed by Cd pollution to the soil-plant-human system should be strengthened, and appropriate measures should be taken to prevent and control Cd pollution in the areas at risk.

External quality assessment (EQA) program for the immunohistochemical detection of ER, PR and Ki-67 in breast cancer: results of an interlaboratory reproducibility ring study in China.

BACKGROUND: An External Quality Assessment (EQA) program was developed to investigate the status of estrogen receptor (ER), progesterone receptor (PR), and Ki-67 immunohistochemical (IHC) detection in breast cancer and to evaluate the reproducibility of staining and interpretation in 44 pathology laboratories in China. METHODS: This program was implemented through three specific steps. In study I, three revising centres defined the reference value for 11 sections. In study II, 41 participating centres (PC) stained and interpreted 11 sections by their own daily practice IHC protocols. In study III, all cases received second interpretation opinions. RESULTS: The stained slides of 44 laboratories were up to the interpretation standard. The overall interpretation concordance rate of this study was over 90%. A perfect agreement was reached among the PCs for the cases with ER+ and PR+ > 50% and Ki-67 > 30%, whereas a moderate agreement was observed for intermediate categories. After second interpretations, the misclassification rates for ER were reduced by 12.20%, for PR were reduced by 17.07%, and for Ki-67 were reduced by 4.88%. Up to 31 PCs observed a benefit from the second opinion strategy. CONCLUSIONS: This project is the first EQA study performed on a national scale for assessment of ER, PR and Ki-67 status by IHC in China. In the whole IHC evaluation process, the intermediate categories were less reproducible than those with high expression rates. Second opinions can significantly improve the diagnostic agreement of pathologists' interpretations.

Promoting subjective preferences in simple economic choices during nap.

Sleep is known to benefit consolidation of memories, especially those of motivational relevance. Yet, it remains largely unknown the extent to which sleep influences reward-associated behavior, in particular, whether and how sleep modulates reward evaluation that critically underlies value-based decisions. Here, we show that neural processing during sleep can selectively bias preferences in simple economic choices when the sleeper is stimulated by covert, reward-associated cues. Specifically, presenting the spoken name of a familiar, valued snack item during midday nap significantly improves the preference for that item relative to items not externally cued. The cueing-specific preference enhancement is sleep-dependent and can be predicted by cue-induced neurophysiological signals at the subject and item level. Computational modeling further suggests that sleep cueing accelerates evidence accumulation for cued options during the post-sleep choice process in a manner consistent with the preference shift. These findings suggest that neurocognitive processing during sleep contributes to the fine-tuning of subjective preferences in a flexible, selective manner.