Simultaneous enhancement of out-coupling efficiency, internal quantum efficiency, and color purity in thermally activated delayed fluorescence (TADF) emitters is highly desired for the practical ...application of these materials. We designed and synthesized two isomeric TADF emitters, 2DPyM-mDTC and 3DPyM-pDTC, based on di(pyridinyl)methanone (DPyM) cores as the new electron-accepting units and di(tert-butyl)carbazole (DTC) as the electron-donating units. 3DPyM-pDTC, which is structurally nearly planar with a very small ΔE ST, shows higher color purity, horizontal ratio, and quantum yield than 2DPyM-mDTC, which has a more flexible structure. An electroluminescence device based on 3DPyM-pDTC as the dopant emitter can reach an extremely high external quantum efficiency of 31.9% with a pure blue emission. This work also demonstrates a way to design materials with a high portion of horizontal molecular orientation to realize a highly efficient pure-blue device based on TADF emitters.
Nonadditivity in fitness effects from two or more mutations, termed epistasis, can result in compensation of deleterious mutations or negation of beneficial mutations. Recent evidence shows the ...importance of epistasis in individual evolutionary pathways. However, an unresolved question in molecular evolution is how often and how significantly fitness effects change in alternative genetic backgrounds.
To answer this question, we quantified the effects of all single mutations and double mutations between all positions in the IgG-binding domain of protein G (GB1). By observing the first two steps of all possible evolutionary pathways using this fitness profile, we were able to characterize the extent and magnitude of pairwise epistasis throughout an entire protein molecule. Furthermore, we developed a novel approach to quantitatively determine the effects of single mutations on structural stability (ΔΔGU). This enabled determination of the importance of stability effects in functional epistasis.
Our results illustrate common biophysical mechanisms for occurrences of positive and negative epistasis. Our results show pervasive positive epistasis within a conformationally dynamic network of residues. The stability analysis shows that significant negative epistasis, which is more common than positive epistasis, mostly occurs between combinations of destabilizing mutations. Furthermore, we show that although significant positive epistasis is rare, many deleterious mutations are beneficial in at least one alternative mutational background. The distribution of conditionally beneficial mutations throughout the domain demonstrates that the functional portion of sequence space can be significantly expanded by epistasis.
•A double-mutant affinity screen enabled quantitation of ΔΔG folding•Strong negative epistasis mostly results from two destabilizing substitutions•A conformationally dynamic group of residues displays pervasive positive epistasis•Cryptically beneficial substitutions are found at 43 of 55 positions in GB1
Olson et al. analyzed how the first two steps of all mutational pathways alter the affinity of GB1 for IgG, thereby quantifying pairwise epistasis. While strong epistasis is rare, numerous cryptically beneficial substitutions are found in alternative mutational backgrounds. Thus, epistasis expands the fraction of sequence space that is functional.
Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients' treatment. The current heavy ...workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses.
Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany.
Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells.
This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.
Plastic waste is an emerging environmental issue for our society. Critical action to tackle this problem is to upcycle plastic waste as valuable feedstock. Thermochemical conversion of plastic waste ...has received growing attention. Although thermochemical conversion is promising for handling mixed plastic waste, it typically occurs at high temperatures (300–800 °C). Catalysts can play a critical role in improving the energy efficiency of thermochemical conversion, promoting targeted reactions, and improving product selectivity. This Review aims to summarize the state‐of‐the‐art of catalytic thermochemical conversions of various types of plastic waste. First, general trends and recent development of catalytic thermochemical conversions including pyrolysis, gasification, hydrothermal processes, and chemolysis of plastic waste into fuels, chemicals, and value‐added materials were reviewed. Second, the status quo for the commercial implementation of thermochemical conversion of plastic waste was summarized. Finally, the current challenges and future perspectives of catalytic thermochemical conversion of plastic waste including the design of sustainable and robust catalysts were discussed.
Thermochemical conversion: Plastic waste is one of the most critical issues in recent years. Upcycle plastic waste as valuable feedstock has attracted huge attention. This Review summarizes thermochemical conversion methods that can convert plastic waste into energy, chemicals, and value‐added materials. It also highlights the recent development of catalytic thermochemical conversions and the current challenges of catalytic thermochemical conversion of plastic waste.
This paper presents a non-ordinary state-based peridynamic formulation that can be applied to the metal machining analysis. The new formulation is first derived by utilizing the technique of mixed ...local/nonlocal gradient approximations to enforce the contact and essential boundary conditions associated in modeling the machining process. A stabilized peridynamic force vector state is then introduced to suppress the zero-energy modes which show up as the result of particle integration of the state-based peridynamic formulation. The introduction of the stabilized peridynamic force vector state eliminates the need of an estimation of the force–spring-like bond forces and leads to a consistent computation of peridynamic equations of motion using a general constitutive model. Finally, a continuum damage model is incorporated into the present state-based peridynamic formulation together with a decomposed stabilized approximate deformation gradient based on a neighbor particle reconstruction scheme to model the ductile metal failure and to maintain a well-defined geometric mapping in finite deformation. Three numerical benchmarks are analyzed to demonstrate the effectiveness and regularization of the present method for simulating the metal machining process.
The Amazon river basin receives ~2000 mm of precipitation annually and contributes ~17% of global river freshwater input to the oceans; its hydroclimatic variations can exert profound impacts on the ...marine ecosystem in the Amazon plume region (APR) and have potential far-reaching influences on hydroclimate over the tropical Atlantic. Here, we show that an amplified seasonal cycle of Amazonia precipitation, represented by the annual difference between maximum and minimum values, during the period 1979-2018, leads to enhanced seasonalities in both Amazon river discharge and APR ocean salinity. An atmospheric moisture budget analysis shows that these enhanced seasonal cycles are associated with similar amplifications in the atmospheric vertical and horizontal moisture advections. Hierarchical sensitivity experiments using global climate models quantify the relationships of these enhanced seasonalities. The results suggest that an intensified hydroclimatological cycle may develop in the Amazonia atmosphere-land-ocean coupled system, favouring more extreme terrestrial and marine conditions.
The effects and risks of endovascular thrombectomy 6 to 24 hours after stroke onset due to basilar-artery occlusion have not been extensively studied.
In a trial conducted over a 5-year period in ...China, we randomly assigned, in a 1:1 ratio, patients with basilar-artery stroke who presented between 6 to 24 hours after symptom onset to receive either medical therapy plus thrombectomy or medical therapy only (control). The original primary outcome, a score of 0 to 4 on the modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 4 moderately severe disability, and 6 death) at 90 days, was changed to a good functional status (a modified Rankin scale score of 0 to 3, with a score of 3 indicating moderate disability). Primary safety outcomes were symptomatic intracranial hemorrhage at 24 hours and 90-day mortality.
A total of 217 patients (110 in the thrombectomy group and 107 in the control group) were included in the analysis; randomization occurred at a median of 663 minutes after symptom onset. Enrollment was halted at a prespecified interim analysis because of the superiority of thrombectomy. Thrombolysis was used in 14% of the patients in the thrombectomy group and in 21% of those in the control group. A modified Rankin scale score of 0 to 3 (primary outcome) occurred in 51 patients (46%) in the thrombectomy group and in 26 (24%) in the control group (adjusted rate ratio, 1.81; 95% confidence interval CI, 1.26 to 2.60; P<0.001). The results for the original primary outcome of a modified Rankin scale score of 0 to 4 were 55% and 43%, respectively (adjusted rate ratio, 1.21; 95% CI, 0.95 to 1.54). Symptomatic intracranial hemorrhage occurred in 6 of 102 patients (6%) in the thrombectomy group and in 1 of 88 (1%) in the control group (risk ratio, 5.18; 95% CI, 0.64 to 42.18). Mortality at 90 days was 31% in the thrombectomy group and 42% in the control group (adjusted risk ratio, 0.75; 95% CI, 0.54 to 1.04). Procedural complications occurred in 11% of the patients who underwent thrombectomy.
Among patients with stroke due to basilar-artery occlusion who presented 6 to 24 hours after symptom onset, thrombectomy led to a higher percentage with good functional status at 90 days than medical therapy but was associated with procedural complications and more cerebral hemorrhages. (Funded by the Chinese National Ministry of Science and Technology; BAOCHE ClinicalTrials.gov number, NCT02737189.).
Silver chalcogenolate cluster assembled materials (SCAMs) are a category of promising light‐emitting materials the luminescence of which can be modulated by variation of their building blocks ...(cluster nodes and organic linkers). The transformation of a singly emissive Ag12(SBut)8(CF3COO)4(bpy)4n (Ag12bpy, bpy=4,4′‐bipyridine) into a dual‐emissive (Ag12(SBut)6(CF3COO)6(bpy)3)n (Ag12bpy‐2) via cluster‐node isomerization, the critical importance of which was highlighted in dictating the photoluminescence properties of SCAMs. Moreover, the newly obtained Ag12bpy‐2 served to construct visual thermochromic Ag12bpy‐2/NH2 by a mixed‐linker synthesis, together with dichromatic core–shell Ag12bpy‐2@Ag12bpy‐NH2‐2 via solvent‐assisted linker exchange. This work provides insight into the significance of metal arrangement on physical properties of nanoclusters.
Tandem varying of Ag cluster structure and tuning mixed linkers in a stepwise fashion are used to achieve dual‐emitting homogeneous and core–shell silver chalcogenolate cluster assembled materials. The arrangements of silver in the cluster are demonstrated to play a fundamentally important role in luminescence.
Convenient generation of stable superatomic silver clusters and their systematic site-specific tailoring and directional assembly present an enduring and significant challenge. In this work, we ...prepared a face-centered cubic (fcc) array of Ag14 superatoms protected by face-capping 1,2-dithiolate-o-carborane (C2B10H10S2) ligands, each produced from 1-thiol-o-carborane in crystallization with simultaneous reduction of Ag+ to Ag0. We find that the corner N-donor ligands contribute predominately to the stability and luminescence of the Ag14 superatom. As the first-formed nanocluster Ag14(C2B10H10S2)6(CH3CN)8·4CH3CN (NC-1) with labile vertex-coordinated CH3CN ligands is highly unstable, monodendate pyridine ligands were used to replace these CH3CN species site-specifically, giving Ag14(C2B10H10S2)6(pyridine/p-methylpyridine)8 (NCs-2,3) in gram scale with its core structure intact, which features ultrastability up to 150 °C in air. Moreover, using bidentate N-containing ligands to bridge the superatomic Ag14 building blocks, we constructed an unprecedented hierarchical series of 1D-to-3D superatomic silver cluster-assembled materials (SCAM-1,2,3,4), and SCAM-4 is air-stable up to 220 °C. Furthermore, this series of stable solid-state superatomic-nanocluster materials exhibit tunable dual emission with wide-range thermochromism. The present study constitutes a major step toward the development of ligand-modulation of the structure, stability, assembly, and functionality of superatomic silver nanoclusters.
Kiwifruit (Actinidia spp.) is a climacteric fruit with high sensitivity to ethylene, influenced by multiple ethylene-responsive structural genes and transcription factors. However, the roles of other ...post-transcriptional regulators (e.g. miRNAs) necessary for ripening remain elusive.
High-throughput sequencing sRNAome, degradome and transcriptome methods were used to identify further contributors to ripening control in the kiwifruit (A. deliciosa cv ‘Hayward’).
Two NAM/ATAF/CUC domain transcription factors (AdNAC6 and AdNAC7), both predicted targets for miR164, showed significant upregulation by exogenous ethylene. Gene expression analysis and luciferase reporter assays indicated that Ade-miR164 and one of its precursor miRNAs (Ade-MIR164b) were repressed by ethylene treatment and negatively correlated with AdNAC6/7 expression. Subsequent analysis indicated that both AdNAC6 and AdNAC7 proteins are transcriptional activators and physically bind the promoters of AdACS1 (1-aminocyclopropane-1-carboxylate synthase), AdACO1 (1-aminocyclopropane-1-carboxylic acid oxidase), AdMAN1 (endo-β-mannanase) and AaTPS1 (terpene synthase). Moreover, subcellular analysis indicated that the location of the AdNAC6/7 proteins was influenced by Ade-miR164.
Multiple omics-based approaches revealed a novel regulatory link for fruit ripening that involved ethylene-miR164-NAC. The regulatory pathway for miR164-NAC is present in various fruit (e.g. Rosaceae fruit, citrus, grape), with implications for fruit ripening regulation.