Three RNA helicases – DDX42, DDX46 and DHX15 – are found to be associated with human U2 snRNP, but their roles and mechanisms in U2 snRNP and spliceosome assembly are insufficiently understood. Here we report the cryo-electron microscopy (cryo-EM) structures of the DDX42-SF3b complex and a putative assembly precursor of 17S U2 snRNP that contains DDX42 (DDX42-U2 complex). DDX42 is anchored on SF3B1 through N-terminal sequences, with its N-plug occupying the RNA path of SF3B1. The binding mode of DDX42 to SF3B1 is in striking analogy to that of DDX46. In the DDX42-U2 complex, the N-terminus of DDX42 remains anchored on SF3B1, but the helicase domain has been displaced by U2 snRNA and TAT-SF1. Through in vitro assays, we show DDX42 and DDX46 are mutually exclusive in terms of binding to SF3b. Cancer-driving mutations of SF3B1 target the residues in the RNA path that directly interact with DDX42 and DDX46. These findings reveal the distinct roles of DDX42 and DDX46 in assembly of 17S U2 snRNP and provide insights into the mechanisms of SF3B1 cancer mutations.

Cullin 4B (CUL4B), a scaffold protein that assembles CRL4B ubiquitin ligase complexes, was found to be overexpressed in many types of tumors. However, the expression pattern and role of CUL4B in non-small cell lung cancer (NSCLC) remain largely unknown. Therefore, in the present study, we investigated the role of CUL4B in NSCLC, and the underlying mechanism was also explored. Our results showed that CUL4B was highly expressed in NSCLC cell lines. Silencing CUL4B obviously inhibited proliferation and migration/invasion of NSCLC cells, and it also suppressed the epithelial‐mesenchymal transition (EMT) progress in NSCLC cells. Furthermore, knockdown of CUL4B significantly inhibited the expression of β-catenin, cyclin D1, and c-Myc in NSCLC cells. Taken together, these results suggest that knockdown of CUL4B inhibited the proliferation and invasion through suppressing the Wnt/β-catenin signaling pathway in NSCLC cells. Therefore, CUL4B may represent a novel therapeutic target for the treatment of NSCLC.

Nonvolatile memory devices based on filamentary resistance switching (RS) areamong the frontrunners to fuel future devices and sensors of the internet of things (IoT) era. The capability of many metal-insulator-metal cells to switch between two distinctive resistive states in response to an external electrical stimulus has been demonstrated. Through years of selection, cells based on the drift of metal ions, namely conductive-bridge memory devices, have shown a wide range of applications with nanosecond switching speeds, nanometer scalability,high-density, and low power-consumption. However, for low (sub-10-μA) current operation, a critical challenge is still represented by programming variability and by the stability of the conductive filament over time. Here, by introducing the concept of reverse filament growth (RFG), we managed to control the structural reconfiguration of the conductive filament inside a memory cell with significant enhancements of each of the aforementioned properties. A first-in-class Cu-based switching device is demonstrated, with a dedicated stack that enabled us to systematically trigger RFG, thus tuning the device’s properties. Along with nanosecond switching speeds, we achieved an endurance of up to 10⁶ cycles with a 10² read window, with outstanding disturb immunity and optimal stability of the filament over time. Furthermore, by tuning the filament’s shape, an excellent control of multi-level bit operations was achieved. Thus, this device offers high flexibility in memory applications.

This study focused on the effect of chlorine on disinfection by-product (DBPs) formation. The concentration of DBPs and total residual chlorine were measured at the same time in synthetic drinking water. Chlorine demand and DBPs increased with chlorine dose and contact time. The descending DBPs formation potential rank was: TCM > DCAA > TCAA > TCNM > BDCM. Furthermore, a linear relation between the concentrations of DBPs (HAAs, THMs or TNMs) and chlorine demand was discovered, and the coefficients did not correlate with chlorine dose. Emerging N-DBPs such as HANs did not follow those disciplines because of their special structures. These results have instructive meanings to the further control of DBPs.