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Blending controlled-release urea (CRU) with conventional urea has the potential to be an effective option for improving nitrogen (N) use efficiency (NUE), although determination of optimal blends in combination with a reduced N application rate has not been well studied. A field experiment was conducted to compare the effects of CRU (a mixture of polymer-coated urea and urea with N ratios of 100:00, 75:25, and 50:50 at 144 kg N ha−1, hereafter denoted as CRU1, CRU2, and CRU3, respectively), urea at 180 (U1) and 144 kg N ha−1 (U2) and a control (no N fertilizer applied, CK) on grain yield, NUE, and economic benefits in a wheat–maize rotation system. The CRU treatments were one-time applied, while for the U treatments, fertilizer N was applied in a split application. The results suggest that a one-time application of CRU prior to sowing of both crops fulfilled the demand of crop plants for N across the entire growth period. Relative to U1, the CRU treatments achieved approximately the same grain yield and 4.7–26.6% greater NUE at 20% reduced N application. Moreover, under CRU2, the yield, NUE, and economic benefits were increased by 12.2%, 9.7%, and 19.1%, respectively, for wheat, and under CRU3, they were increased by 10.9%, 20.6%, and 17.3%, respectively, for maize, compared with the U2 treatment. These results demonstrate that a mixture of CRU and urea at a ratio of 75:25 for wheat and 50:50 for maize with a 20% reduction in N application rate can maintain productivity, while enhancing NUE in the North China Plain.

Yuping Zhao,1,* Yanna Zhao,1,* Qisan Ma,1 Bin Sun,1 Qingpeng Wang,1 Zhuang Ding,1 Huaizhen Zhang,2 Xiuling Chu,3 Min Liu,1 Zhengping Wang,1 Jun Han1 1Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng, Shandong 252059, People’s Republic of China; 2School of Environment and Planning, Liaocheng University, Liaocheng, Shandong 252059, People’s Republic of China; 3College of Agriculture, Liaocheng University, Liaocheng, Shandong 252059, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanna Zhao; Jun HanInstitute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, Shandong Province, People’s Republic of ChinaFax +86 635 8239136Email ynzhao2011@163.com; junhanmail@163.comBackground: The combination of chemo-photodynamic therapy based on nano-technology has emerged as a preferable and promising measure for synergetic antitumor therapy.Purpose: The aim of this study was expected to overcome most of the safety concerns from nano-carriers and improve the chemo-photodynamic synergistic antitumor efficacy.Methods: Herein, we reported a facile and effective approach based on the self-assembly of chemotherapeutic agent 10-hydroxycamptothecin (HCPT) and photosensitizer chlorin e6 (Ce6) for preparing stably dual-functional nanorods (NRs).Results: The chemical thermodynamic parameters obtained from isothermal titration calorimeter (ITC) and the microcosmic configuration snapshots acquired by molecular dynamics (MD) simulations verified that HCPT and Ce6 molecules tended to assemble with each other through various intermolecular forces. The as-prepared HCPT/Ce6 NRs possessed a relatively uniform size of around 165 nm and zeta potential of about −29 mV, together with good stability in aqueous solution and freeze-dried state. In addition, both the extra- and intracellular reactive oxygen species (ROS) generation capacity of the NRs under laser irradiation was significantly enhanced compared with Ce6 injections. Moreover, the dual-functional HCPT/Ce6 NRs exhibited a substantial in vitro/in vivo synergistic antitumor efficacy under laser irradiation due to the integration of the two therapeutic modalities into one drug delivery system. Besides, no obvious hepatic or renal toxicity was observed in the NRs treatment groups.Conclusion: Taken together, HCPT/Ce6 NRs demonstrated a powerful efficacy in chemo-photodynamic therapy for breast cancer. Therefore, the carrier-free dual-functional NRs prepared in a facile and effective strategy might give inspiration for the development of combined antitumor therapy.Keywords: carrier-free, self-assembly, chemo-photodynamic, dual-functional nanorods, combined antitumor therapy, synergistic antitumor efficacy