Decoding China's anthropogenic typical pollutant discharge patterns: Long-term dynamics and hotspot transitions driven by population, diet, and sanitation.

Human activities have led to an alarming increase in pollution, resulting in widespread water contamination. A comprehensive understanding of the quantitative relationship between anthropogenic pollutant discharges and the escalating anthropogenic disturbances and environmental efforts is crucial for effective water quality management. Here we establish a Model for Estimating Anthropogenic pollutaNts diScharges (MEANS) and simulate the long-term dynamics of various types of anthropogenic discharges in China based on an unprecedented spatio-temporal dynamic parameter dataset. Our findings reveal that from 1980 to 2020, anthropogenic discharges exhibited an overall trend of initially increasing and subsequently decreasing, with the peak occurring around 2005. During this period, the dominant pollution sources in China shifted from urban to rural areas, thereby driving the transition of hotspot pollutants from nitrogen to phosphorus in the eastern regions. The most significant drivers of anthropogenic pollutant discharges gradually shifted from population size and dietary structure to wastewater treatment and agricultural factors. Furthermore, we observed that a significant portion of China's regions still exceed the safety thresholds for pollutant discharges, with excessive levels of total phosphorus (TP) being particularly severe. These findings highlight the need for flexible management strategies in the future to address specific pollution levels and hotspots in different regions. Our study underscores the importance of considering the complex interplay between anthropogenic disturbances, environmental efforts, and long-term anthropogenic pollutant discharges for effective water pollution control.

Accumulation of Cr in different vegetables and derivation of soil Cr threshold using the species sensitivity distribution method.

Due to its high mobility and bioavailability, hexavalent chromium [Cr(VI)] in agricultural soil can be taken up by crops and pose threat to human being. In this study, two soils (Jiangxi red soil and Shandong fluvo-aquic soil) spiked with Cr(VI) and 8 common vegetable varieties were used to conduct the pot experiment. The bioconcentration factor (BCF) values based on the tetraacetic acid extractable Cr (EDTA-Cr) in soils were used to construct the species sensitivity distribution (SSD) curve. Afterwards, the soil Cr threshold was derived based on the critical BCF value and the permissible limit of Cr for vegetables. The results showed that when spiked with 5.6 mg kg-1 of Cr(Ⅵ), the soil EDTA-Cr concentrations were significantly increased compared with the control except Jiangxi red soil planted with carrot and radish, while the Cr concentrations in the edible parts of vegetables in both soils were below the permissible limit (0.5 mg kg-1 FW). However, there are dramatic differences in the accumulation of Cr by different varieties of vegetables. Apparent discrepancy was observed between the two soils for the bioconcentration of Cr by carrot. Among the leafy vegetables, lettuce and oilseed rape are the most and the least sensitive to Cr pollution, respectively. The safety threshold values of EDTA-Cr were 0.70 mg kg-1 for Shandong fluvo-aquic soil and 0.85 mg kg-1 for Jiangxi red soil, respectively. This study provides information on the safety production of vegetable products in Cr(Ⅵ) polluted soils and is helpful to the revision of soil quality standards of Cr.

A comprehensive assessment of heavy metal(loid) contamination in leafy vegetables grown in two mining areas in Yunnan, China-a focus on bioaccumulation of cadmium in Malabar spinach.

Contamination of leafy vegetables grown in heavy metal(loid)-polluted mining areas pose serious health risks. This study aimed to explore the heavy metal(loid) contamination of leafy vegetables near two mining areas, by collecting samples from 14 different leafy vegetable species in Yunnan Province, China. The lead (Pb), cadmium (Cd), arsenic (As), and copper (Cu) contents of the samples were determined, and risks to human health were calculated using the hazard quotient and hazard index (HI). Moreover, Malabar spinach was identified as a leafy vegetable that exhibits low accumulation of heavy metal(loid)s. The accumulation capacity of different Malabar spinach varieties was verified, and a Cd soil safety threshold was determined using a pot experiment. Overall, Pb and Cd were the main soil and vegetable contaminants found in both study sites. The HI values for all leafy vegetables, apart from Malabar spinach, were greater than 1, indicating the presence of risks to human health; moreover, the health risks were greater for children than adults. The Malabar spinach pot experiment results showed that only some Cd forms exceeded China's maximum permissible standards. Furthermore, Malabar spinach varieties A (instant Malabar spinach), C (extra-large leaf green vine Malabar spinach), and F (large leaf Malabar spinach) displayed the lowest Cd accumulation. We calculated Cd total and bioavailable soil safety thresholds of 4.75 and 0.77 mg kg-1, respectively. However, further research is required to validate soil heavy metal safety thresholds for different vegetables. Ultimately, the heavy metal(loid) contamination of leafy vegetables described here was more serious than anticipated. Finally, the results of this study can inform residents living near these mining areas of a low-risk leafy vegetable, which will reduce the harm caused by heavy metal(loid) contamination in the area.

An in vitro study of temperature variation of super-pulsed thulium fiber laser in ureter / 现代泌尿外科杂志

【Objective】 The thermal effects of super-pulsed thulium fiber laser (TFL) at different powers,lithotripsy modes and irrigation rates were studied using a 3D kidney model to simulate ureteral lithotripsy in vivo. 【Methods】 A thermal effect model was established in vitro. Under the same conditions of laboratory temperature and equipment,the temperature around the optical fiber was measured and compared when different optical fiber diameters,powers,lithotripsy modes and irrigation rates were used to simulate lithotripsy by TFL. 【Results】 There was significant difference in the temperature around the optical fiber caused by two fibers with different diameters under the same conditions (P<0.05). Under the same conditions,different lithotripsic modes produced different temperatures,and the temperature of "high energy and low frequency" was lower than that of "low energy and high frequency" (P<0.05). When the power was 10 W and the minimum irrigation rate was 10 mL/min,the plateau temperature did not reach the safety threshold (43 ℃). When the power was 20 W and the minimum irrigation rate was 10 mL/min,the platform temperature exceeded the safety threshold. When the irrigation rate was 20 mL/min,the platform temperature did not reach the safety threshold. 【Conclusion】 In the study of ureteral lithotripsy in vitro,the power,mode,irrigation rate and optical fiber diameter are factors affecting the thermal effects of TFL. No matter what kind of lithotripsy mode and fiber diameter,the temperature around the fiber is safe when the lithotripsy power is ≤10 W and the irrigation rate is ≥10 mL/min;when the lithotripsy power is ≤20 W and the irrigation rate is ≥20 mL/min,the temperature around the fiber is safe.

Determination of Soil Cadmium Safety Thresholds for Food Production in a Rice-Crayfish Coculture System.

Previous studies have mainly focused on cadmium (Cd) contamination in conventional rice monocultures, and no research on rice-crayfish coculture has been reported. In this study, a Cd-contaminated (0−30 mg kg−1) rice-crayfish co-culture system was established by adding exogenous Cd. The results showed that the Cd concentration in each tissue of rice and each organ of crayfish increased with increasing soil Cd concentration. Specifically, the Cd concentration in each rice tissue was as follows: root > stem > leaf ≈ panicle > grain > brown rice, and the jointing and heading stages were critical periods for the rapid enrichment of Cd in the aboveground tissues of rice. The Cd concentration in each organ of crayfish was as follows: hepatopancreas > gut > gill ≈ exoskeleton > abdominal muscle. Cd was gradually enriched in the abdominal muscle after 30 days of coculture between crayfish and rice. Pearson's correlation analysis showed that the soil's total Cd concentration, available Cd concentration, and water Cd concentration were positively correlated with Cd content in various tissues of rice and various organs of crayfish, whereas EC and TDS in water were markedly related to rice stems, leaves, stalks, and small crayfish. According to the maximum limit of Cd in grain (0.2 mg kg−1) and crustacean aquatic products (0.5 mg kg−1) in China, the safe threshold of soil Cd for rice and crayfish under the rice-crayfish coculture system is 3.67 and 14.62 mg kg−1, respectively. Therefore, when the soil Cd concentration in the rice-crayfish coculture system exceeds 3.67 mg kg−1, the safety risk to humans through the consumption of food from this coculture system will increase. This study provides a theoretical basis for safe food production in a rice-crayfish coculture system using the established Cd pollution model.

Delineation of basic farmland based on the quality and spatial stability: a case study of Yingtan City, China.

Delimiting basic farmland is essential to ensure food security and maintain social stability. Determining the quantity and spatial layout of the basic farmland is the main aspect of delimitation. For a long time, superiors in local governments have mainly assigned the basic farmland quantity, which is prone to regional imbalance. The determination of the spatial layout is mainly based on the quality and contiguity of the cultivated land; however, spatial stability is not considered. Therefore, in this study, Yingtan City was used as an example to determine the scale of basic farmland based on the food security and multi-source data, construct a Land Evaluation and Site Assessment System model, evaluate the quality of cultivated land, and integrate the degree of agglomeration and compatibility of cultivated land to characterize its spatial stability. The quality and spatial stability of the cultivated land were combined to construct a matrix. The cultivated land patches must be selected according to the "scale limitation, stability priority, and quality superiority" principle. Finally, basic farmland covering an area of 75,946.34 hm2 was delineated, whose average quality index and spatial stability increased by 0.02 and 0.04, respectively. The landscape structure is more stable than the originally planned structure, which is conducive to the sustainable development of the cultivated land ecosystem. That is, a good delimitation effect was achieved, providing a reference for actual delimitation work.

[Technological Classification of Cadmium Quality in the Rice Producing Areas of South China].

Classifying the quality of agricultural products is an important means of managing the arable land quality and guaranteeing the quality and safety of agricultural products. This work is planned to be completed in 2020. However, there is still no perfect method or technology for classifying the quality of arable lands. The species sensitivity distribution (SSD) has become commonly used for determining ecological safety thresholds since it takes into account differences in species sensitivity, the physical and chemical properties of soils, biological availability, and sources of pollutants. However, it has not yet been applied to the classification of arable land quality. Therefore, based on the routine monitoring data of rice production areas in southern China from the Agro-environmental Monitoring Center of China, this study proposes the use of species sensitivity distributions to classify the environmental quality of cadmium in rice production areas. The scientific rationale of this method was also discussed in order to provide an important reference for the construction and improvement of the classification system for arable land quality in China. The results showed that the pH, soil organic matter, and cation exchange capacity of the physical and chemical properties of soils significantly affected the enrichment of cadmium in rice, and this relationship was used to establish the cadmium transfer equation in the soil-rice system. It was found that there were obvious differences in the cadmium enrichment abilities of different rice varieties, which were mainly caused by the differences in their genotypes. According to the species sensitivity distributions, soil cadmium thresholds were obtained, which yielded a priority protection class of less than 0.26 mg·kg-1 and strict control class of greater than 1.67 mg·kg-1, between which are the safe use classes. The results were verified through independent datasets, and it was found that the application of species sensitivity distributions to classify the environmental quality of cadmium in rice producing areas reflected good scientific rationale and operability. This study may provide a foundation for the construction and improvement of the arable land quality classification system in China.

Effects of cadmium pollution on the safety of rice and fish in a rice-fish coculture system.

The rice-fish coculture system (RFS) is one of the most important and environmentally friendly agricultural systems in the world. With the increasing amounts of heavy metal contamination in the soil and water, the safe production of RFS has been greatly threatened. However, there are no reports on heavy metal uptake by rice and fish in a RFS. In this study, a model of cadmium (Cd)-contaminated RFS with the addition of 0-40.00 mg kg-1Cd was simulated in the field. The accumulation of Cd in the rice and fish increased as the level of Cd contamination increased. Regardless of the level of contamination, the order of Cd accumulation in the rice was root > stem ≈ leaf > rice grain > brown grain and in the fish was liver ≈ gut > kidney > gill > muscle. The dissolved oxygen (DO) and the transparency of water were significantly reduced after the fish were added. The tendency of the Cd to accumulate in the fish correlated with the change of the concentration of Cd in the water (P < 0.05). According to the maximum level of Cd in the brown grains (0.40 mg kg-1) and in the fish muscle (0.10 mg kg-1) of Codex Alimentarius Commission (CAC), the safety threshold of soil Cd for the rice and the fish was calculated to be 5.86 mg kg-1 and 31.47 mg kg-1, respectively, indicating that the safety risk to the rice was much greater in a Cd-contaminated RFS.

Ecological risk assessment of heavy metal pollution in the water of China's coastal shellfish culture areas.

In order to learn about the status of heavy metals and ecological risks in the water of thirteen China's costal shellfish culture areas, principal component analysis was applied to analyze the distributions of five kinds of heavy metal, while the safety threshold method was employed to evaluate the ecological risks. The results showed that among the 13 shellfish culture areas, the average metal concentrations were in the order of Zn > Cu > Pb > Hg > Cd, and all heavy metals were below the second standards for sea water quality of China. The distribution of heavy metals in 13 shellfish culture areas was reflected by two principal components with the contribution rates of F1(Cu) and F2(Zn, Pb) were 36.14% and 23.40%,respectively,which was less affected by economic and geographical differences. The ecological risks assessment of five kinds of heavy metals showed that MOS10 was more than one; the probabilities of five heavy metals affecting more than 10% of aquatic organisms were 49.52%, 24.11%, 17.49%, 22.05%, and 5.66%, respectively, the ecological risk of five main heavy metals was in order Cu > Zn > Cd > Pb > Hg. In the selected thirteen shellfish culture areas, the value of msPAF of seven culture areas was higher than 20%, indicating these areas are highly ecologically contaminated by heavy metals, and the other four shellfish culture areas with value of 0, indicating that these areas have no ecological risk of heavy metals pollution.

Deriving water quality criteria for China for the organophosphorus pesticides dichlorvos and malathion.

Organophosphorus pesticides are effective, cheap, and used extensively but can harm aquatic organism and human health. Here, water quality criteria (WQCs) for dichlorvos (DDVP) and malathion (MAL) were derived. Nine aquatic organisms native to China were used in toxicity tests. Published toxicity data for aquatic organisms native and non-native to China were also analyzed. DDVP and MAL WQCs were derived using (log-normal model) species sensitivity distributions. Species sensitivity distribution curves indicated native and non-native species have different sensitivities to DDVP. The sensitivities of native and non-native species to MAL were not different because non-native species data for fewer than eight genera were available, so further research is required. The results indicated that native species need to be considered when deriving WQCs. The criteria maximum concentration (CMC) and criteria continuous concentration (CCC) were 1.33 and 0.132 µg/L, respectively, for DDVP, and 0.100 and 0.008 µg/L, respectively, for MAL. The CMCs for DDVP and MAL derived using ETX 2.0 software and species sensitivity ranks were different from the CMCs obtained using the SSD method because of parameter uncertainties. The DDVP and MAL WQCs were significantly lower than Chinese surface water quality standard thresholds. The results provide basic data for revising these thresholds.

Dopamine receptor D2 gene polymorphism, urine fluoride, and intelligence impairment of children in China: A school-based cross-sectional study.

OBJECTIVE: We aimed to study the association of urine fluoride with intelligence quotient (IQ) in children with a careful consideration of up to 30 potential confounding factors as well as possible heterogeneity of the relation between urine fluoride levels and IQ scores across children with different dopamine receptor-2 (DRD2) Taq 1A genotypes (CC, CT, and TT). METHODS: A school-based cross-sectional study design was applied. A total of 323 children (2014-2015, 7-12 years old) were enrolled from four schools in both historical endemic and non-endemic areas of fluorosis in Tianjin of China using a cluster sampling method. Urine fluoride levels and age-specific IQ scores in children were measured at the enrollment. Polymerase chain reaction-restriction fragment length polymorphism methods were used to genotype DRD2 Taq 1A polymorphism with genomic DNA isolated from whole blood collected at the enrollment. Multiple linear regression models were applied to evaluate the relationship between urine fluoride levels and IQ scores overall and within the DRD2 Taq 1A SNP = CC/CT and TT subgroups. Model robustness was tested through bootstrap, sensitivity analysis, and cross-validation techniques. A safety threshold of urine fluoride levels for IQ impairment was determined in the subgroup TT. RESULTS: In overall participants, the DRD2 Taq 1A polymorphism itself was not related to IQ scores in children who had a high level of urine fluoride. In the CC/CT subgroup, urine fluoride levels and IQ scores in children were unrelated (adjusted ß (95% confidence interval (CI)) = - 1.59 (- 4.24, 1.05), p = 0.236). Among the participants carrying the TT genotype, there was a strong and robust negative linear relationship between log-urine fluoride and IQ scores in children (adjusted ß (95% CI) = - 12.31 (- 18.69, - 5.94), p < 0.001). Urine fluoride levels had a stronger association with IQ in children carrying the TT genotype (adjusted ß = - 12.31, bootstrapped standard error (SE) = 1.28), compared to that in overall participants (adjusted ß = - 2.47, bootstrapped SE = 3.75) (Z = 2.483 and bootstrapped p = 0.007). The safety threshold of urine fluoride levels in the subgroup TT was 1.73 mg/L (95% CI = (1.51, 1.97) (mg/L)). CONCLUSIONS: There is heterogeneity in the relation between urine fluoride and IQ across children carrying different DRD2 Taq 1A genotypes. Large-scale epidemiological studies are needed to confirm our findings.

Deriving freshwater safety thresholds for hexabromocyclododecane and comparison of toxicity of brominated flame retardants.

Hexabromocyclododecane (HBCD) is a brominated flame retardant used throughout the world. It has been detected in various environmental media and has been shown toxic to aquatic life. The toxic effects of HBCD to aquatic organisms in Chinese freshwater ecosystems are discussed here. Experiments were conducted with nine types of acute toxicity testing and three types of chronic toxicity testing. After comparing a range of species sensitivity distribution models, the optimal model of Bull III was used to derive the safety thresholds for HBCD. The acute safety threshold and the chronic safety threshold of HBCD for Chinese freshwater organisms were found to be 2.32mg/L and 0.128mg/L, respectively. Both values were verified by the methods of the Netherlands and the United States. HBCD was found to be less toxic compared to other widely used brominated flame retardants. The present results provide valuable information for revision of the water quality standard of HBCD in China.

PT, aPTT, TT and the hemostatic safety threshold of dabigatran and rivaroxaban.

The proposals of the Working group on perioperative hemostasis (Groupe d'intérêt en hémostase péri-opératoire (GIHP)) concerning the perioperative management of patients receiving the direct oral anticoagulants (DOACs) are based on the measure of their anticoagulant activities (anti-Xa for rivaroxaban and anti-IIa for dabigatran) with a safety threshold ≤ 30 ng/mL. If the dosage of the drug is not available, proposals are based on the combination of a PT ≥80% and an aPTT ≤1.20. The aim of our study was to evaluate the performance of PT, aPTT and thrombin time to predict values above or below the safety threshold. The measurement of DOACs concentration was carried out in 64 samples from patients treated with rivaroxaban and 48 samples from patients treated with dabigatran. The PT and aPTT were measured for all samples, while the TT was measured only for patients receiving dabigatran. The absence of agreement between the global hemostasis tests and the DOACs concentrations was observed for 10% of patients receiving dabigatran and 27% of patients with rivaroxaban treatment. Apart from dabigatran for which the predictive negative value of PT and aPTT or TT allows to exclude a concentration >30 ng/mL in 100% of cases, our results highlight the risk of misinterpretation when using global coagulation tests (PT and aPPT) for determination of the safety threshold for patients receiving the DOACs.

Assessing safety of extractables from materials and leachables in pharmaceuticals and biologics - Current challenges and approaches.

Leachables from pharmaceutical container closure systems can present potential safety risks to patients. Extractables studies may be performed as a risk mitigation activity to identify potential leachables for dosage forms with a high degree of concern associated with the route of administration. To address safety concerns, approaches to toxicological safety evaluation of extractables and leachables have been developed and applied by pharmaceutical and biologics manufacturers. Details of these approaches may differ depending on the nature of the final drug product. These may include application, the formulation, route of administration and length of use. Current regulatory guidelines and industry standards provide general guidance on compound specific safety assessments but do not provide a comprehensive approach to safety evaluations of leachables and/or extractables. This paper provides a perspective on approaches to safety evaluations by reviewing and applying general concepts and integrating key steps in the toxicological evaluation of individual extractables or leachables. These include application of structure activity relationship studies, development of permitted daily exposure (PDE) values, and use of safety threshold concepts. Case studies are provided. The concepts presented seek to encourage discussion in the scientific community, and are not intended to represent a final opinion or "guidelines."

Developing alerting thresholds for prospective drug safety monitoring.

BACKGROUND: Current methods for prospective drug safety monitoring focus on determining whether and when to generate safety alerts indicating that a new drug may be less safe than a comparator. Approaches are needed to develop safety thresholds that can be used to define whether a new drug is no less than or equally safe as the comparator. OBJECTIVES: Our aim is to develop a framework for determining which safety statements can be made about a new drug and when they can be made during prospective monitoring. METHODS: We developed a two-pronged approach to establish safety thresholds for active monitoring. First, we adapted concepts from setting margins in non-inferiority (NI) trials ("NI approach"). Second, we summarized NI margins used in published randomized trials and reviewed publicly available data from the US FDA's website to identify the type and magnitude of evidence used in regulatory decisions involving withdrawals and black box warnings between 2009 and 2013 ("benchmark approach"). We applied the framework to a case study of dabigatran versus warfarin and major bleed. RESULTS: We provide formulas on both risk ratio and risk difference scales for the NI approach that are analogous to threshold setting in NI trials but based on point estimates and using a maximum tolerable increase rather than a preservation factor. Using this approach, we established a safety threshold for the dabigatran case study that was within range of the findings from the benchmark approach (1.18 to 7.30). Comparing the safety threshold with post-approval studies of dabigatran versus warfarin indicated that no safety statement can be made. CONCLUSIONS: The proposed framework expands the safety statements that can be made in current prospective drug safety monitoring systems. Copyright © 2015 John Wiley & Sons, Ltd.

Environmental safety threshold of commonly encountered highly pathogenic microor-ganisms / 军事医学

Objective To study environmental safety reference standard values of commonly encountered pathogenic microorganisms, and provide the basis for environmental risk assessment of a high-level biosafety laboratory (BSL).Methods Using human exposure dose calculation methods as the basic principle in combination with microbial hazard evaluation methods , an infectious dose calculation model of human exposure to pathogenic microorganisms by breathing was proposed . Based on research on characteristics of commonly encountered pathogenic microorganisms at home and abroad , the environ-mental safety threshold reference standard and environmental risk protection zone for such microorganisms were obtained . Results An the environmental risk assessment standard calculation method for commonly encountered highly pathogenic microorganisms was proposed , and the minimum infectious dose and environmental safety threshold of seven commonly encountered pathogenic microorganisms were obtained , including SARS coronavirus , highly pathogenic avian influenza virus, Mycobacterium tuberculosis, Bacillus anthracis, Yersinia pestis,Francisella tularensis, and epidemic hemorrhagic fever virus.Conclusion The results can be used as a reference standard of infectious aerosols in a high-level BSL for environ-mental risk assessment , laboratory risk control and emergency management .