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Sewage sludge (SS) is commonly used as agricultural fertilizer worldwide. However, the toxic metal(loid)s in SS raises concerns about soil contamination and the potential risks to human health. This study, conducted since 2007 on the North China Plain, examines the impact of SS use on crops. An experiment was designed with five treatments: conventional fertilization (CK) and four levels of SS application (W1, W2, W3, and W4: 4.5, 9.0, 18.0, and 36.0 t ha -1 , respectively). Soil concentrations of eight toxic metal(loid)s (Zn, Cu, Cr, Cd, Ni, Pb, As, and Hg) were analyzed to assess pollution risk using various indices. Health risks associated with maize and wheat grains were also evaluated. Additionally, the impact of long-term SS application on crop yield, soil quality, and human health within a wheat-maize rotation system was examined. SS application increased wheat and maize yields by 5.37 to 19.08 % and 6.97 to 17.94 %, respectively, across treatments W2 to W4. Despite the toxic metal(loid)s in the grains remaining within safe limits, their concentrations showed an upward trend, especially under the W4 treatment. Moreover, SS application significantly increased the soil Zn, Cu, Cr, Cd, Pb, and Hg levels (P < 0.05) without exceeding the national standards. The geo-accumulation index values revealed rising pollution levels for Zn, Cu, Cd, and Hg, which shifted from no contamination to moderate contamination and then to moderate-to-high contamination, yet the overall pollution level remained safe. Soil ecological risks increased from moderate to serious, with Hg posing the greatest risk, particularly under the W4 treatment. Long-term crop intake from the area significantly exposed children and adults to As, contributing 42.12 % and 34.62 % to hazard index (HI), respectively. The HI values for toxic metal(loid)s in these grains surpassed one in both age groups, suggesting health risks from long-term SS cultivated crops., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Carnosic acid could disrupt the β-catenin/BCL9 protein-protein interaction and inhibit β-catenin dependent transcription, thereby reduce the incidence of colorectal cancer induced by abnormal activation of Wnt/β-catenin signalling pathway. However, its activity was weak (IC 50 for SW480: 28.2 ± 2.05 μM) and total synthesis was difficult. During the structural simplification of natural products, S0 was revealed to be the basic pharmacophore of carnosic acid. Subsequent structural optimization of S0 led to the discovery of S11 as a possible anticancer agent with prominent proliferation inhibition effect (IC 50 for SW480: 9.56 ± 0.91 μM) and best selectivity index (SI = 3.0) against Wnt hyperactive cancer cells. Futher mechanism investigation through TOP/FOP dual luciferase reporter assay, immunofluorescence, co-immunoprecipitation, microscale thermophoresis, downstream oncoprotein expression and cell apoptosis showed that compound S11 could significantly inhibit the proliferation of SW480 cells via obvioudsly decreasing the nucleus translocation of β-catenin and effectively disrupting β-catenin/BCL9 protein-protein interaction. Additionally, cell migration, molecule docking, in vitro stability and solubility assays were also conducted. Overall, S11 was worthy of in-depth study as a potential inhibitor for the Wnt/β-catenin pathway and its discovery also proved that the structural simplification of natural products was still one of the effective methods to find new lead compounds or candidate drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Excess phosphorus (P) leached from high fertiliser input cropping systems in northern China is having detrimental effects on water quality. Before improved management can be directed at specific soils and cropping system types estimates of P leached loss apportionment and mitigation potentials across the main soil (fluvo-aquic soil, FAS; cinnamon soil, CS; black soil, BS) areas and cropping systems (protected vegetable fields, PVFs; open vegetable fields, OVFs; cereal fields, CFs) are needed. The present study designed and implemented conventional fertilisation and low input system trials at 75 sites inclusive of these main soils and cropping system types in northern China. At all sites, a uniform lysimeter design (to 0.9 m depth) enabled the collection and analysis of leachate samples from 7578 individual events between 2008 and 2018. In addition, site-specific static and dynamic activity data were recorded. Results showed that annual total phosphorus (TP) leached losses across the main soil areas and cropping systems were 4.99 × 10 6  kg in northern China. A major finding was PVFs contributed to 48.5% of the TP leached losses but only accounted for 5.7% of the total cropping areas. The CFs and OVFs accounted for 40.3% and 11.2% of the TP leached losses, respectively. Across northern China, the TP leached losses in PVFs and OVFs were greatest in FAS areas followed by CS and BS areas. The higher TP leached losses in FAS areas were closely correlated with greater P fertiliser inputs and irrigation practices. From a management perspective in PVFs and OVFs systems, a decrease of P inputs by 10-30% would not negatively affect yields while protecting water quality. The present study highlights the importance of decreasing P inputs in PVFs and OVFs and supporting soil P nutrient advocacy for farmers in China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The use of livestock manure as a substitution for synthetic nitrogen (N) fertilizers is recommended to improve the sustainable use of manure nutrients and alleviate the adverse impacts of synthetic N fertilizers on the environment. A thorough understanding of how such substitutions affect reactive N losses and greenhouse gas (GHG) emissions in cereal production systems in the North China Plain (a main livestock production region in China), is needed to achieve an environmental friendly and sustainable production. Based on a long-term field experiment, different manure/chemical fertilizer treatments were designed, i.e., non-fertilization control (CK), chemical fertilizers alone (NPK), and manure substitution for chemical N fertilizers (with equivalent N rate; NPKP, 50% N from pig manure; NPKC, 50% N from chicken manure). Crop yield, nitrogen use efficiency (NUE), soil fertility, N losses, and GHG emissions were chosen as prominent indicators to evaluate the consequences of manure substitutions for N-based fertilizers. The replacement of synthetic fertilizers by livestock manure decreased NO 3 -N leaching and NH 3 volatilization by 46.2% and 5.61-22.2%, respectively, while sustained the crop yields and improved NUE. However, both NPKP and NPKC treatments did not have any impact on N 2 O and CO 2 mitigation. Compared with NPK, NPKC and NPKP meaningfully increased SOC by 9.56% and 19.6%, respectively. More specifically, NPKC increased TN content by 14.7% (P < 0.05) compared to NPK treatment. The results showed that 50% substitution of manure for synthetic N fertilizers is a potential option in maize production systems to decrease N losses (including NH 3 , N 2 O emissions and N leaching) by approximately 45% (42.8-48.1%). However, only 1.81% of the total farmers surveyed (i.e., 16,595) have being applied livestock manure for maize cultivation in the North China Plain. Therefore, famers in this plain should be encouraged to use manure to improve ecological aspects of cereal cultivation and decrease the associated environmental pollutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The net anthropogenic phosphorus inputs (NAPI) model has been used extensively to assess changes in phosphorus (P) inputs and cycling in the environment. However, temporary populations have generally been unconsidered in these assessments. In this study, the NAPI model was used to estimate P loads from the 16 towns and villages in the Erhai Lake Basin (ELB), Southwest China and to evaluate the potential impact from temporary residents (tourism). The results showed that the average value P inputs in the basin (estimated at 2384 kg P km -2  year -1 ) were 5 times the national average level, and that temporary residents contributed 1%. Agriculture accounted for most of the net P, with chemical fertilizers (55% of the inputs) as the main source, followed by food and animal feed. Only 9.54% of the P inputs to the basin were exported. River water quality and NAPI were significantly correlated (P < 0.01). Tourism industry contributes significantly to regional economic growth and prosperity, but its beneficial effects on the economy does not equate with the adverse impact on environment. This study illustrates what is happening in Southwest China and provides scientific evidence that shows we need to find novel ways to reduce nutrients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The effects of long-term animal manure application and crop straw incorporation on the migration of carbon (C) and nitrogen (N) deep into the soil profile and the associated N leaching risk in particular have not been thoroughly elucidated to date. Soil profile samples were collected from depths of up to 200 cm from the following four treatments in a 27-year field experiment on the North China Plain: N + phosphorus (P) + potassium (K) fertilizers (NPK), NPK + 22.5 t ha -1 swine manure (NPKM), NPK + 33.7 t ha -1 swine manure (NPKM+) and NPK + straw incorporation (NPKS). The results revealed that long-term manure application and straw incorporation significantly enhanced the soil organic C (SOC) and total N (TN) contents in the upper 20 cm and that this effect was weaker in the deeper soil layers (P < 0.05). Residual nitrate-N (NO 3 - -N) contents at 0 to 40 cm and 120 to 200 cm in the NPKM and NPKM+ were 4-16 and 2-9 times higher than those in the NPK and NPKS, respectively. These results indicated a greater potential for N leaching from manure addition and a higher propensity for NO 3 - -N leaching out of the 40-100 cm soil layer. Pearson relationship analysis demonstrated that NO 3 - -N content was clearly affected by SOC and dissolved organic N (DON) contents along the soil profile (20-200 cm), implying that the higher residual NO 3 - -N contents in the deeper soil from manure addition were partially attributable to the mineralization and nitrification of the downward SOC and DON. Interestingly, a low level of residual NO 3 - -N combined with negative mineralization in the 120-200 cm soil layers of the NPKS treatment was observed, suggesting that straw incorporation promotes soil NO 3 - -N retention. Thus, we concluded that long-term manure application is beneficial for soil NO 3 - -N content retention, whereas long-term straw incorporation benefits NO 3 - -N retention., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The impacts of manure application on soil ammonia (NH 3 ) volatilization and greenhouse gas (GHG) emissions are of interest for both agronomic and environmental reasons. However, how the swine manure addition affects greenhouse gas and N emissions in North China Plain wheat fields is still unknown. A long-term fertilization experiment was carried out on a maize-wheat rotation system in Northern China (Zea mays L-Triticum aestivum L.) from 1990 to 2017. The experiment included four treatments: (1) No fertilizer (CK), (2) single application of chemical fertilizers (NPK), (3) NPK plus 22.5t/ha swine manure (NPKM), (4) NPK plus 33.7t/ha swine manure (NPKM+). A short-term fertilization experiment was conducted from 2016 to 2017 using the same treatments in a field that had been abandoned for decades. The emissions of NH 3 and GHGs were measured during the wheat season from 2016 to 2017. Results showed that after long-term fertilization the wheat yields for NPKM treatment were 7105kg/ha, which were higher than NPK (3880kg/ha) and NPKM+ treatments (5518kg/ha). The wheat yields were similar after short-term fertilization (6098-6887kg/ha). The NH 3 -N emission factors (EF amm ) for NPKM and NPKM+ treatments (1.1 and 1.1-1.4%, respectively) were lower than NPK treatment (2.2%) in both the long and short-term fertilization treatments. In the long- and short-term experiments the nitrous oxide (N 2 O) emission factors (EF nit ) for NPKM+ treatment were 4.2% and 3.7%, respectively, which were higher than for the NPK treatment (3.5% and 2.5%, respectively) and the NPKM treatment (3.6% and 2.2%, respectively). In addition, under long and short-term fertilization, the greenhouse gas intensities for the NPKM+ treatment were 33.7 and 27.0kg CO 2 -eq/kg yield, respectively, which were higher than for the NPKM treatment (22.8 and 21.1kg CO 2 -eq/kg yield, respectively). These results imply that excessive swine manure application does not increase yield but increases GHG emissions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Optimizing the nitrogen (N) application rate can increase crop yield while reducing the environmental risks. However, the optimal N rates vary substantially when different targets such as maximum yield or maximum economic benefit are considered. Taking the wheat-maize rotation cropping system on the North China Plain as a case study, we quantified the variation of N application rates when targeting constraints on yield, economic performance, N uptake and N utilization, by conducting field experiments between 2011 and 2013. Results showed that the optimal N application rate was highest when targeting N uptake (240kgha -1 for maize, and 326kgha -1 for wheat), followed by crop yield (208kgha -1 for maize, and 277kgha -1 for wheat) and economic income (191kgha -1 for maize, and 253kgha -1 for wheat). If environmental costs were considered, the optimal N application rates were further reduced by 20-30% compared to those when targeting maximum economic income. However, the optimal N rate, with environmental cost included, may result in soil nutrient mining under maize, and an extra input of 43kgNha -1 was needed to make the soil N balanced and maintain soil fertility in the long term. To obtain a win-win situation for both yield and environment, the optimal N rate should be controlled at 179kgha -1 for maize, which could achieve above 99.5% of maximum yield and have a favorable N balance, and at 202kgha -1 for wheat to achieve 97.4% of maximum yield, which was about 20kgNha -1 higher than that when N surplus was nil. Although these optimal N rates vary on spatial and temporal scales, they are still effective for the North China Plain where 32% of China's total maize and 45% of China's total wheat are produced. More experiments are still needed to determine the optimal N application rates in other regions. Use of these different optimal N rates would contribute to improving the sustainability of agricultural development in China., (Copyright © 2017 Elsevier B.V. All rights reserved.)