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Bispecific antibodies provide an efficient tool for combinational clinical therapy. Here we have engineered a heterodimeric Fc for bispecific antibodies production by combining the knob-into-hole and electrostatic steering strategies where a bulky hydrophobic residue Phe405 of the IgG CH3 interface is mutated to a charged residue Lys and Lys409 of the corresponding CH3 domain is mutated to Ala. The crystal structure of this Fc heterodimer solved here at 2.7Å resolution revealed how these two mutations resulted a complementary binding interface and explained why F405K mutation could effectively inhibit Fc homodimer formation during protein expression. An anti-HER2 bispecific antibody derived from trastuzumab and pertuzumab was generated by this heterodimeric Fc. It showed comparable or improved efficacy than the combination of trastuzumab and pertuzumab in inhibiting proliferation of cancer cells in vitro and in vivo. Overall this study shows that the heterodimeric Fc engineered here provides an efficient platform for generating active bispecific antibody for cancer treatment.

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Cultivated land in Middle-lower Yangtze Plain has been greatly reduced over the last few decades due to rapid urban expansion and massive urban construction. Accurate and timely monitoring of cultivated land changes has significant for regional food security and the impact of national land policy on cultivated land dynamics. However, generating high-resolution spatial-temporal records of cultivated land dynamics in complex areas remains difficult due to the limitations of computing resources and the diversity of land cover over a complex region. In our study, the annual dynamics of cultivated land in Middle-lower Yangtze Plain were first produced at 30 m resolution with a one-year interval in 1990-2010.Changes of vegetation and cultivated land are examined with the breakpoints inter-annual Normalized Difference Vegetation Index (NDVI) trajectories and synthetic NDVI derived by the enhanced spatial and temporal adaptive reflectance fusion model (ESTRAFM), respectively. Last, cultivated land dynamics is extracted with a one-year interval by detecting phenological characteristic. The results indicate that the rate of reduction in cultivated land area has accelerated over the past two decades, and has intensified since 1997.The dynamics of cultivated land mainly occurred in the mountains, hills, lakes and around towns, and the change frequency of these area was mainly one or two times. In particular, the changes in cultivated land in Nanjing have been most intense, perhaps attributed to urban greening and infrastructure construction.