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Defects are considered to be one of the most significant factors that compromise the power conversion efficiencies and long-term stability of perovskite solar cells. Therefore, it is urgent to have a profound understanding of their formation and influence mechanism, so as to take corresponding measures to suppress or even completely eliminate their adverse effects on device performance. Herein, the possible origins of the defects in metal halide perovskite films and their impacts on the device performance are analyzed, and then various methods to reduce defect density are introduced in detail. Starting from the internal and interfacial aspects of the metal halide perovskite films, several ways to improve device performance and long-term stability including additive engineering, surface passivation, and other physical treatments (annealing engineering), etc., are further elaborated. Finally, the further understanding of defects and the development trend of passivation strategies are prospected.In search of new environmentally friendly and effective antifungal agents, a series of 4-aminoquinolines bearing a 1,3-benzodioxole moiety were prepared and their structures were fully elucidated by spectroscopic analyses. The antifungal activities of all the target compounds against five phytopathogenic fungi were evaluated in vitro. The results revealed that most of the newly synthesized compounds exhibited obvious inhibitory activities at the concentration of 50 μg/mL. Among them, 6-(furan-2-yl)-N-(4-methylphenyl)-2H-[1,3]dioxolo[4,5-g]quinolin-8-amine hydrochloride (7m) displayed more promising antifungal potency with EC50 values of 10.3 and 14.0 μg/mL against C. lunata and A. alternate, respectively. read more Particularly, the EC50 value of 7m against C. lunata was 7.3-fold as potent as the standard azoxystrobin. There were some significant morphological alterations in the mycelia of C. lunata when treated with 7m at 50 μg/mL. Additionally, the preliminary structure-activity relationships (SARs) were also discussed. Thus, this study suggests that 4-aminoquinolines bearing a 1,3-benzodioxole moiety are interesting scaffolds for the development of novel antifungal agents.

The Multidimensional Pain Inventory (MPI) is frequently used in the assessment of chronic pain. Three subgroups have been derived from MPI adaptive coper (AC), dysfunctional (DYS), and interpersonally distressed (ID). The primary aim of this study was to examine whether outcome of Interdisciplinary Multimodal Pain Rehabilitation Programs (IMMRPs) differed across the MPI subgroups.

Patients with chronic pain (N=34,513), included in the Swedish Quality Registry for Pain Rehabilitation, were classified into MPI subgroups and a subset that participated in IMMRPs (N=13,419) was used to examine overall treatment outcomes using a previously established Multivariate Improvement Score (MIS) and 2 retrospective patient-evaluated benefits from treatment.

The subgroups differed on sociodemographic characteristics, pain duration, and spatial spreading of pain. DYS and ID had the best overall outcomes to MIS. AC had the best outcomes according to the 2 retrospective items. Transition into other subgroups following IMc pain and treatment outcome.The CRISPR/Cas9 system is an RNA-guided sequence-specific genome editing tool, which has been adopted for single or multiple gene editing in a wide range of organisms. When working with gene families with functional redundancy, knocking out multiple genes within the same family may be required to generate a phenotype. In this study, we tested the possibility of exploiting the known tolerance of Cas9 for mismatches between the single-guide RNA (sgRNA) and target site to simultaneously introduce indels in multiple homologous genes in the marine diatom Phaeodactylum tricornutum. As a proof of concept, we designed two sgRNAs that could potentially target the same six light-harvesting complex (LHC) genes belonging to the LHCF subgroup. Mutations in up to five genes were achieved simultaneously using a previously established CRISPR/Cas9 system for P. tricornutum. A visible colour change was observed in knockout mutants with multiple LHCF lesions. A combination of pigment, LHCF protein and growth analyses was used to further investigate the phenotypic differences between the multiple LHCF mutants and WT. Furthermore, we used the two same sgRNAs in combination with a variant of the existing Cas9 where four amino acids substitutions had been introduced that previously have been shown to increase Cas9 specificity. A significant reduction of off-target editing events was observed, indicating that the altered Cas9 functioned as a high-fidelity (HiFi) Cas9 nuclease.Umbrella trials are an innovative trial design where different treatments are matched with subtypes of a disease, with the matching typically based on a set of biomarkers. Consequently, when patients can be positive for more than one biomarker, they may be eligible for multiple treatment arms. In practice, different approaches could be applied to allocate patients who are positive for multiple biomarkers to treatments. However, to date there has been little exploration of how these approaches compare statistically. We conduct a simulation study to compare five approaches to handling treatment allocation in the presence of multiple biomarkers - equal randomisation; randomisation with fixed probability of allocation to control; Bayesian adaptive randomisation (BAR); constrained randomisation; and hierarchy of biomarkers. We evaluate these approaches under different scenarios in the context of a hypothetical phase II biomarker-guided umbrella trial. We define the pairings representing the pre-trial expectations on efficacy as linked pairs, and the other biomarker-treatment pairings as unlinked. The hierarchy and BAR approaches have the highest power to detect a treatment-biomarker linked interaction. However, the hierarchy procedure performs poorly if the pre-specified treatment-biomarker pairings are incorrect. The BAR method allocates a higher proportion of patients who are positive for multiple biomarkers to promising treatments when an unlinked interaction is present. In most scenarios, the constrained randomisation approach best balances allocation to all treatment arms. Pre-specification of an approach to deal with treatment allocation in the presence of multiple biomarkers is important, especially when overlapping subgroups are likely.

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