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Epialleles, the heritable epigenetic variants that are not caused by changes in DNA sequences, can broaden genetic and phenotypic diversity and benefit to crop breeding, but very few epialleles related to agricultural traits have been identified in maize. Here, we cloned a small kernel mutant, smk-wl10, from maize, which encoded a tubulin-folding cofactor B (ZmTFCB) protein. Expression of the ZmTFCB gene decreased in the smk-wl10 mutant, which arrested embryo, endosperm and basal endosperm transfer layer developments. Overexpression of ZmTFCB could complement the defective phenotype of smk-wl10. No nucleotide sequence variation in ZmTFCB could be found between smk-wl10 and wild type (WT). Instead, we detected hypermethylation of nucleotide CHG (where H is A, C or T nucleotide) sequence contexts and increased level of histone H3K9me2 methylation in the upstream sequence of ZmTFCB in smk-wl10 compared with WT, which might respond to the attenuating transcription of ZmTFCB. In addition, yeast two-hybrid and bimolecular fluorescence complementation assays identified a strong interaction between ZmTFCB and its homolog ZmTFCE. Thus, our work identifies a novel epiallele of the maize ZmTFCB gene, which might represent a common phenomenon in the epigenetic regulation of important traits such as kernel development in maize.

Background: IBI322 is an anti-CD47/PD-L1 bispecific antibody that blocks both the PD-1/PD-L1 and CD47/SIRP-α pathways. By an “imbalanced” design with a lower binding affinity to CD47 and a higher binding affinity to PD-L1, preclinical models showed IBI322 blocks CD47 on CD47+/PD-L1+ tumors more selectively than a regular CD47 monoclonal antibody does, with minimal impact on RBCs. We conducted first-in-human, phase I study of IBI322 monotherapy in patients with advanced solid tumors. Here, we report the results from early dose escalation/expansion part of the study. Methods: Eligible patients (18-75 years of age, ECOG PS 0-1) had locally advanced, recurrent, or metastatic solid tumors without available therapies to confer clinical benefit. The dose escalation (0.01 to 45 mg/kg, QW/Q2W/Q3W, IV) followed an accelerated titration and a standard 3+3 design. Dose expansion part was conducted at 10-30mg/kg Q2-3W groups. The primary objectives of this study were to evaluate the safety, tolerability and preliminary anti-tumor activity (per RECIST v1.1) of IBI322. Results: As the data cut-off date on October 12, 2021, 58 patients were enrolled (age: 53±11.7 years, 37 [63.8%] males, ECOG PS 1: n=38 [65.5%], previously ICI treated: n=15 [25.9%]). Only one DLT of grade 4 reversible thrombocytopenia was observed at 20mg/kg Q2W group. Treatment-related adverse events (TRAEs) of any grade occurred in 43 (74.1%) patients. The most frequent TRAEs including anemia (31.0%), thrombocytopenia (22.4%), and pyrexia (15.5%). Grade ≥3 TRAEs occurred in 13 (22.4%) patients, the most frequent Grade ≥3 TRAE was thrombocytopenia (12.1%). All thrombocytopenia was asymptomatic, transient, and reversible within 10 days. No thrombocytopenia led to any hemorrhage. Investigator-determined immune-related adverse events occurred in 10 (17.2%) patients. Two (3.4%) patients experienced infusion reaction. Among 20 patients treated at active doses (≥10 mg/kg) and with at least one tumor assessment, 4 (20%) achieved PR, and 7 (35%) achieved SD. Among 9 patients with NSCLC (including 4 patients failed on prior ICI treatment) who were treated at active doses (≥10 mg/kg), 3 (33.3%) achieved PR, and 5 (55.6%) achieved SD. As of data cut-off date, all these 4 patients achieved PR mentioned above still remained on IBI322 monotherapy. Conclusion: IBI322 monotherapy showed a manageable safety profile with a promising anti-tumor activity in heavily treated patients with advanced malignancies. Study is ongoing to further evaluate IBI322 monotherapy and in combination with other regimen in various types of solid tumor. Clinical trial information: NCT04328831, NCT04912466 Citation Format: Jie Wang, Yuping Sun, Qian Chu, Jianchun Duan, Rui Wan, Zhijie Wang, Jun Zhao, Haoyuan Li, Yingmei Guo, Yuling Chen, Yan Wang. Phase I study of IBI322 (anti-CD47/PD-L1 bispecific antibody) monotherapy therapy in patients with advanced solid tumors in China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT513.

Combined with electron microbeam techniques such as scanning electron microscopy and electron-induced X-ray emission, a helium microbeam is used to study the effect of Ar+ ion bombardment on the surface of a binary alloy Ag37Cu63 by particle-induced X-ray emission and Rutherford backscattering. A pronounced change of the surface concentration and depth profile has been found at both Cu-enriched solid solution micro-region and Ag-enriched eutectic mixture micro-region on the alloy surface due to ion bombardment. The preferential sputtering of Ag and bombardment-induced surface segregation is suggested to be attributed to the composition change in the near-surface regions. A superposition of depth distributions determined from different micro-phase-regions is experimentally confirmed.