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Incomplete knowledge of the mechanisms at work continues to hamper efforts to maximize reprogramming efficiency. Here, we present a systematic genome-wide RNAi screen to determine the global regulators during the early stages of human reprogramming. Our screen identifies functional repressors and effectors that act to impede or promote the reprogramming process. Repressors and effectors form close interacting networks in pathways, including RNA processing, G protein signaling, protein ubiquitination, and chromatin modification. Combinatorial knockdown of five repressors (SMAD3, ZMYM2, SFRS11, SAE1, and ESET) synergistically resulted in ∼85% TRA-1-60-positive cells. Removal of the novel splicing factor SFRS11 during reprogramming is accompanied by rapid acquisition of pluripotency-specific spliced forms. Mechanistically, SFRS11 regulates exon skipping and mutually exclusive splicing of transcripts in genes involved in cell differentiation, mRNA splicing, and chromatin modification. Our study provides insights into the reprogramming process, which comprises comprehensive and multi-layered transcriptional, splicing, and epigenetic machineries.

The PBL (Perfobond Leiste) shear key has advantages such as high load capacity and high restraint capacity. However, at the same time, there are also problems such as insufficient deformation capacity and low stiffness along the weak axis direction. In addition, shear key performance degradation, ductility, and other problems are not yet clear under the reciprocal seismic action. To this end, a folded perfobond shear key is proposed in this paper to solve the problems of insufficient deformation capacity and uneven stiffness distribution of the traditional PBL shear key. At the same time, numerical analysis is carried out to investigate the seismic performance of the shear key under earthquakes, such as stiffness degradation, ductility, and energy dissipation. Through the push-out test, it is found that the steel plate outside the shear key deforms, showing a certain semi-rigid characteristic; concrete forms a trapezoidal constraint area centered on shear keys, and the constraint effect is significantly improved compared with the point constraint of studs. On the whole, under the condition of a similar shear section, the bearing capacity of the shear key is 1.5 times that of the stud. The ductility coefficient is above 3.0, showing good deformation ability. Through parameter analysis, it is found that the bearing capacity of shear keys increases with the increase of web width-thickness ratio, but the deformation capacity degenerates. The opening rate mainly affects the embedded effect of shear keys and concrete. Based on the fitting analysis, the variation laws of web width influence coefficient γB, web height influence coefficient γH, and embedded effect influence coefficient γD are obtained, and the calculation formula of shear key bearing capacity is proposed. Finally, based on the push-out test, the hysteretic behavior of the shear key is studied. It is found that the load-displacement hysteretic curve of the shear key is full, the ductility coefficient is 4.2, and the equivalent viscous damping coefficient is 0.27, which shows good seismic capacity. In summary, the new shear key realizes the good unity of bearing capacity and deformation and has high engineering application value.