All four precancerous cell lines were highly sensitive to Wee1 inhibition by Adavosertib (AZD1775), while primary keratinocytes tolerated this inhibitor. Wee1 inhibition caused induction of DNA damage during S-phase followed by mitotic failure in (pre)cancer cells. In conclusion, we uncovered Wee1 inhibition as a promising chemopreventive strategy for precancerous cells, with comparable responses as fully transformed HNSCC cells.Protein-protein interactions are spatially regulated in living cells to realize high reaction efficiency, as seen in naturally existing electron-transfer chains. Nevertheless, arrangement of chemical/biochemical components at the artificial device interfaces does not possess the same level of control. Here we report a tetrahedral DNA framework-enabled bulk enzyme heterojunction (BEH) strategy to program the multi-enzyme catalytic cascade at the interface of electrochemical biosensors. The construction of interpenetrating network of BEH at the millimeter-scale electrode interface brings enzyme pairs within the critical coupling length (CCL) of ~10 nm, which in turn greatly improve the overall catalytic cascade efficiency by ~10-fold. We demonstrate the BEH generality with a range of enzyme pairs for electrochemically detecting clinically relevant molecular targets. As a proof of concept, a BEH-based sarcosine sensor enables single-step detection of the metabolic biomarker of sarcosine with ultrasensitivity, which hold the potential for precision diagnosis of early-stage prostate cancer.Androgen receptor (AR) signalling is essential in nearly all prostate cancers. Any alterations to AR-mediated transcription can have a profound effect on carcinogenesis and tumor growth. While mutations of the AR protein have been extensively studied, little is known about those somatic mutations that occur at the non-coding regions where AR binds DNA. Using clinical whole genome sequencing, we show that AR binding sites have a dramatically increased rate of mutations that is greater than any other transcription factor and specific to only prostate cancer. TTK21 cell line Demonstrating this may be common to lineage-specific transcription factors, estrogen receptor binding sites were also found to have elevated rate of mutations in breast cancer. We provide evidence that these mutations at AR binding sites, and likely other related transcription factors, are caused by faulty repair of abasic sites. Overall, this work demonstrates that non-coding AR binding sites are frequently mutated in prostate cancer and can impact enhancer activity.Following assembly, the anthrax protective antigen (PA) forms an oligomeric translocon that unfolds and translocates either its lethal factor (LF) or edema factor (EF) into the host cell. Here, we report the cryo-EM structures of heptameric PA channels with partially unfolded LF and EF at 4.6 and 3.1-Å resolution, respectively. The first α helix and β strand of LF and EF unfold and dock into a deep amphipathic cleft, called the α clamp, which resides at the interface of two PA monomers. The α-clamp-helix interactions exhibit structural plasticity when comparing the structures of lethal and edema toxins. EF undergoes a largescale conformational rearrangement when forming the complex with the channel. A critical loop in the PA binding interface is displaced for about 4 Å, leading to the weakening of the binding interface prior to translocation. These structures provide key insights into the molecular mechanisms of translocation-coupled protein unfolding and translocation.This paper presents a dataset obtained from hydraulic and sediment transport experiments performed in a full-scale urban drainage physical model of 36 m2. The study seeks to accurately measure sediment mobilization through the different parts of the model (surface, gully pots and pipe system), also obtaining a precise characterization of water flow and using realistic rainfall simulator to ensure the transferability of the results. Three different rain intensities and five sediment granulometries were tested in 6 hydraulic and 23 wash-off and sediment transport experiments. The following experimental data were produced surface elevations and 2D runoff velocities measured by visualization techniques; surface and in-pipe water depths; flow discharges, total suspended solids concentrations and particle size distribution at the entrance of the gully pots and at the pipe system outlet; and sediment mass balances. This data is optimal for developing and validating wash-off and sediment transport formulations in urban drainage models, towards better treatment and management techniques for minimizing the impact of urban surface pollutants on the environments of towns and cities.Combining polymers with small amounts of stiff carbon-based nanofillers such as graphene or graphene oxide is expected to yield low-density nanocomposites with exceptional mechanical properties. However, such nanocomposites have remained elusive because of incompatibilities between fillers and polymers that are further compounded by processing difficulties. Here we report a water-based process to obtain highly reinforced nanocomposite films by simple mixing of two liquid crystalline solutions a colloidal nematic phase comprised of graphene oxide platelets and a nematic phase formed by a rod-like high-performance aramid. Upon drying the resulting hybrid biaxial nematic phase, we obtain robust, structural nanocomposites reinforced with graphene oxide.The melon fly, Zeugodacus cucurbitae (Coquillett), is an important destructive pest worldwide. Functional studies of the genes associated with development and reproduction during different life stages are limited in Z. cucurbitae. There have yet to be comprehensive transcriptomic resources for genetic and functional genomic studies to identify the molecular mechanisms related to its development and reproduction. In this study, we comprehensively sequenced the transcriptomes of four different developmental stages egg, larva, pupa, and adults. Using the Illumina RNA-Seq technology, we constructed 52 libraries from 13 stages with four biological replicates in each and generated 435.61 Gb clean reads. We comprehensively characterized the transcriptomes with high-coverage mapping to the reference genome. A total of 13,760 genes were mapped to the reference genome, and another 4481 genes were characterized as new genes. Finally, 14,931 genes (81.85%) were functionally annotated against six annotation databases. This study provides the first comprehensive transcriptome data of all developmental stages of Z.