Frizzled receptors (FZDs) are class-F G-protein-coupled receptors (GPCRs) that function in Wnt signalling and are essential for developing and adult organisms. As central mediators in this complex signalling pathway, FZDs serve as gatekeeping proteins both for drug intervention and for the development of probes in basic and in therapeutic research. Here we present an atomic-resolution structure of the human Frizzled 4 receptor (FZD4) transmembrane domain in the absence of a bound ligand. The structure reveals an unusual transmembrane architecture in which helix VI is short and tightly packed, and is distinct from all other GPCR structures reported so far. Within this unique transmembrane fold is an extremely narrow and highly hydrophilic pocket that is not amenable to the binding of traditional GPCR ligands. We show that such a pocket is conserved across all FZDs, which may explain the long-standing difficulties in the development of ligands for these receptors. Molecular dynamics simulations on the microsecond timescale and mutational analysis uncovered two coupled, dynamic kinks located at helix VII that are involved in FZD4 activation. The stability of the structure in its ligand-free form, an unfavourable pocket for ligand binding and the two unusual kinks on helix VII suggest that FZDs may have evolved a novel ligand-recognition and activation mechanism that is distinct from that of other GPCRs.

The development of highly sensitive and selective uranyl ion (UO22+) probes has attracted significant attention owing to the threat to human health caused by high toxicity, radioactivity, and long half‐life. Herein, the development of aggregation‐induced emission (AIE) active polymer dots (Pdots) is described for an accurate UO22+ monitoring using a portable electrochemiluminescence (ECL) system. An AIE‐active polymer containing tetraphenylethene and boron ketoiminate moieties is prepared into Pdots and modified with ssDNA to capture UO22+, which can amplify the ECL signal of the Pdots through a resonance energy transfer mechanism. This probe provides an ultralow detection limit of 10.6 pm/2.5 ppt, which is at least two orders of magnitude lower than the known UO22+ luminescent probes. Only UO22+ can provide an obvious ECL enhancement among the various metal ions, indicating the excellent selectivity of this probe. Furthermore, a portable ECL analyzer is designed to realize UO22+ measurements in the wild. The anodic ECL mechanism of UO22+ is discovered and ECL technology is first applied in monitoring radioactive substances. This study provides a novel strategy for the development of accurate UO22+ probes and a practical UO22+ monitoring method, indicating its potential application in the environmental and energy fields.

For the first time, functional microporous conjugated polymers were synthesized for the efficient separation of uranium from simulated radioactive effluents.

It is strategically important to recycle uranium from radioactive liquid wastes for future uranium supply of nuclear energy. However, it is still a challenge to adsorb uranium selectively from highly acidic and radioactive waste. In this paper, we report a novel strategy for effective uranium removal from highly acidic and radioactive media by surface ion-imprinted mesoporous silica sorbent. The sorbent was successfully synthesized by a co-condensation method with uranyl as the template ion and diethylphosphatoethyltriethoxysilane as the functional ligands. The pseudo-second-order model and Langmuir model showed better correlation with the sorption kinetic and isotherm data, and the sorption equilibrium could be reached within 40 min, the maximum adsorption capacity from Langmuir model was 80 mg/g in 1 mol/L nitric acid (HNO) solution at 298.15 K. The sorbent showed faster kinetics and higher selectivity toward uranium over other ions compared with nonimprinted mesoporous and other previous sorbents. Furthermore, the ion-imprinted materials exhibited remarkable radioresistance stability and could be regenerated efficiently after five cycles. This work may provide a new approach for highly efficient sorption of uranium from strong HNO and radioactive media.

Archaeal DNA replication machinery represents a core version of that found in eukaryotes. However, the proteins essential for the coordination of origin selection and the functioning of DNA polymerase have not yet been characterized in archaea, and they are still being investigated in eukaryotes. In the current study, the Orc1/Cdc6 (SsoCdc6) proteins from the crenarchaeon Sulfolobus solfataricus were found to physically interact with its DNA polymerase B1 (SsoPolB1). These SsoCdc6 proteins stimulated the DNA-binding ability of SsoPolB1 and differentially regulated both its polymerase and nuclease activities. Furthermore, the proteins also mutually regulated their interactions with SsoPolB1. In addition, SsoPolB1c467, a nuclease domain-deleted mutant of SsoPolB1 defective in DNA binding, retains the ability to physically interact with SsoCdc6 proteins. Its DNA polymerase activity could be stimulated by these proteins. We report on a linkage between the initiator protein Orc1/Cdc6 and DNA polymerase in the archaeon. Our present and previous findings indicate that archaeal Orc1/Cdc6 proteins could potentially play critical roles in the coordination of origin selection and cell-cycle control of replication.