Shotgun proteomics has grown rapidly in recent decades, but a large fraction of tandem mass spectrometry (MS/MS) data in shotgun proteomics are not successfully identified. We have developed a novel database search algorithm, Open-pFind, to efficiently identify peptides even in an ultra-large search space which takes into account unexpected modifications, amino acid mutations, semi-or non-specific digestion and co-eluting peptides. Tested on two metabolically labeled MS/MS datasets, Open-pFind reported 50.5-117.0% more peptide-spectrum matches (PSMs) than the seven other advanced algorithms. More importantly, the Open-pFind results were more credible judged by the verification experiments using stable isotopic labeling. Tested on four additional large-scale datasets, 70-85% of the spectra were confidently identified, and high-quality spectra were nearly completely interpreted by Open-pFind. Further, Open-pFind was over 40 times faster than the other three open search algorithms and 2-3 times faster than three restricted search algorithms. Re-analysis of an entire human proteome dataset consisting of ~25 million spectra using Open-pFind identified a total of 14,064 proteins encoded by 12,723 genes by requiring at least two uniquely identified peptides. In this search results, Open-pFind also excelled in an independent test for false positives based on the presence or absence of olfactory receptors. Thus, a practical use of the open search strategy has been realized by Open-pFind for the truly global-scale proteomics experiments of today and in the future..

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Thick, wide-bandgap materials as photoactive layers in semi-transparent Pero-SCs realized >20% AVT and ∼10% PCE.

As a hole-transport layer (HTL) material, poly(3,4-ethylenedioxythiophene):polystyrene-sulfonate (PEDOT:PSS) was often criticized for its intrinsic acidity and hygroscopic effect that would in the long run affect the stability of perovskite solar cells (Pero-SCs). As alternatives, herein water-soluble two-dimensional (2D) transition metal dichalcogenides (TMDs), such as MoS and WS were used as HTLs in p-i-n Pero-SCs. It was found that the content of 1T phase in 2D TMDs HTLs is centrally important to the power conversion efficiencies (PCEs) of Pero-SCs, and the 1T-rich TMDs (as achieved from exfoliation and without postheating) lead to much higher PCEs. More importantly, as PEDOT:PSS was replaced by 2D TMDs, both the PCEs and stability of Pero-SCs were significantly improved. The highest PCEs of 14.35 and 15.00% were obtained for the Pero-SCs with MoS and WS, respectively, whereas the Pero-SCs with PEDOT:PSS showed a highest PCE of only 12.44%. These are up to date the highest PCEs using 2D TMDs as HTLs. After being stored in a glovebox for 56 days, PCEs of the Pero-SCs using MoS and WS HTLs remained 78 and 72%, respectively, whereas the PCEs of Pero-SCs with PEDOT:PSS almost dropped to 0 over 35 days. This study demonstrates that water-soluble 2D TMDs have great potential for application as new generation of HTLs aiming at high performance and long-term stable Pero-SCs.

Doping of semiconductors by introducing foreign atoms enables their widespread applications in microelectronics and optoelectronics. We show that this strategy can be applied to direct bandgap lead-halide perovskites, leading to the realization of ultrawide photoluminescence (PL) at new wavelengths enabled by doping bismuth (Bi) into lead-halide perovskites. Structural and photophysical characterization reveals that the PL stems from one class of Bi doping-induced optically active center, which is attributed to distorted [PbI6] units coupled with spatially localized bipolarons. Additionally, we find that compositional engineering of these semiconductors can be employed as an additional way to rationally tune the PL properties of doped perovskites. Finally, we accomplished the electroluminescence at cryogenic temperatures by using this system as an emissive layer, marking the first electrically driven devices using Bi-doped photonic materials. Our results suggest that low-cost, earth-abundant, solution-processable Bi-doped perovskite semiconductors could be promising candidate materials for developing optical sources operating at new wavelengths.

A facile annealing method of room-temperature mixed-solvent-vapor annealing (rtMSVA) was proposed to fabricate high crystallinity and ultra-smooth perovskite thin films, and the photovoltaic performance of perovskite solar cells was improved with the rtMSVA treatment.

Wuhan nodavirus (WhNV) is a newly identified member of the Nodaviridae family with a bipartite genome of positive-sense RNAs. A nonstructural protein encoded by subgenomic RNA3 of nodaviruses, B2, serves as a potent RNA silencing suppressor (RSS) by sequestering RNA duplexes. We have previously demonstrated that WhNV B2 blocks RNA silencing in cultured Drosophila cells. However, the molecular mechanism by which WhNV B2 functions remains unknown. Here, we successfully established an RNA silencing system in cells derived from Pieris rapae, a natural host of WhNV, by introducing into these cells double-stranded RNA (dsRNA)-expressing plasmids or chemically synthesized small interfering RNAs (siRNAs). Using this system, we revealed that the WhNV B2 protein inhibited Dicer-mediated dsRNA cleavage and the incorporation of siRNA into the RNA-induced silencing complex (RISC) by sequestering dsRNA and siRNA. Based on the modeled B2 3-dimensional structure, serial single alanine replacement mutations and N-terminal deletion analyses showed that the RNA-binding domain of B2 is formed by its helices ␣2 and ␣3, while helix ␣1 mediates B2 dimerization. Furthermore, positive feedback between RNA binding and B2 dimerization was uncovered by gel shift assay and far-Western blotting, revealing that B2 dimerization is required for its binding to RNA, whereas RNA binding to B2 in turn promotes its dimerization. All together, our findings uncovered a novel RNA-binding mode of WhNV B2 and provided evidence that the promotion effect of RNA binding on dimerization exists in a viral RSS protein.

A s a form of nucleic acid-based silencing, RNA interference (RNAi) plays essential roles in the cellular response to viral infection in plants and invertebrates (3,13,34,50). In virus-infected cells, aberrant accumulation of viral single-stranded RNA (ssRNA) triggers its conversion into viral replicative intermediate double-stranded RNA (vRI-dsRNA), which is processed by the dsRNA-specific endonuclease Dicer into 21-to 23-nucleotide (nt) small interfering RNAs (siRNAs). Next, the virus-derived siRNAs (viRNAs) are transferred from Dicer to Argonaute (AGO) proteins in the RNA-induced silencing complex (RISC), which then guides the specific degradation of homologous viral ssRNAs (1,8,11,50). In mammals, RNAi directed by viral and cellular microRNAs (miRNAs) also contributes to host innate immunity against viral infection (18,27,35).To combat RNAi-mediated immunity, many plant and animal viruses encode viral suppressors of RNA silencing (VSRs) that target different components in the RNAi machinery. By sequestering dsRNA and siRNA, plant VSRs like turnip crinkle virus (TCV) capsid protein and tombusvirus P19 protein inhibit the production of siRNAs and hinder the incorporation of siRNAs into RISC (25, 41, 52). Additionally, direct interaction with AGO protein is known as a common approach of many plant and insect VSRs, such as cucumber mosaic virus (CMV) 2b protein, TCV P38 protein, sweet potato mild mottle virus (SPMMV) P1 protein, and cricket paralysis virus (CrPV) 1A protein, for suppressing RISC-mediated mRNA cleavage (2,17,36,54).Although Dicer plays essential roles in RNAi immunity, the mechanism by which Dicer can be directly targeted by VSRs is still poorly understood. The core protein of hepatitis C virus (HCV) was previously reported to interact with Dicer; however, whether this interaction is required for the RNA silencing suppression activity of HCV core protein has not been determined (7, 51). Furthermore, several VSRs have been reported to be able to target both RNA and protein components in the RNAi machinery. For example, TCV P38 was shown to target both RNA duplexes and AGO1 (2, 33). A question that remains to be answered, however, is whether an interrelationship exists between diverse activities of VSRs that mediate RNA binding and interaction with RNAi protein components (51).The ideal model for studying viral pathogenesis and RNAi immunity is the persistent infection of Drosophila melanogaster cells with Flock House virus (FHV), the most extensively studied member of the Nodaviridae family, which encodes a well-defined VSR designated B2 (1,6,10,16,29). During the course of FHV infection, 5=-terminal vRI-dsRNA initiated by viral RNA-dependent RNA polymerase (RdRP) triggers RNAi immunity, which is suppressed by B2 protein because B2 associates with RdRP and binds to vRI-dsRNA, thereby leading to the inhibition of the production of siRNAs by Dicer-2 (Dcr-2) (1). Recently, an interaction of FHV B2 with the Piwi-Argonaut-Zwille (PAZ) domain of Dcr-2 was detected in vitro (45). Although whether this in...