All‐inorganic CsPbX3 (X=I, Br, Cl) perovskite quantum dots (PQDs) have been investigated because of their optical properties, such as tunable wavelength, narrow band, and high quantum efficiency. ...These features have been used in light emitting diode (LED) devices. LED on‐chip fabrication uses mixed green and red quantum dots with silicone gel. However, the ion‐exchange effect widens the narrow emission spectrum. Quantum dots cannot be mixed because of anion exchange. We address this issue with a mesoporous PQD nanocomposite that can prevent ion exchange and increase stability. We mixed green quantum‐dot‐containing mesoporous silica nanocomposites with red PQDs, which can prevent the anion‐exchange effect and increase thermal and photo stability. We applied the new PQD‐based LEDs for backlight displays. We also used PQDs in an on‐chip LED device. Our white LED device for backlight display passed through a color filter with an NTSC value of 113 % and Rec. 2020 of 85 %.
Points of light: Green CsPbBr3 perovskite quantum dots (PQDs), embedded in mesoporous silica (MP), were mixed with red CsPb(Br0.4I0.6)3 quantum dots in a silicone resin and placed on an InGaN blue chip. The green and red QDs were excited by blue light with λ=450 nm. The resulting PQD white light emitting diode (LED) exhibits a wide color gamut because of its narrow emission wavelength.
MicroRNA399-mediated regulation of the ubiquitin-conjugating enzyme UBC24/PHOSPHATE2 (PHO2) is crucial for Pi acquisition and translocation in plants. Because of a potential role for PHO2 in protein ...degradation and its association with membranes, an iTRAQ (for isobaric tags for relative and absolute quantitation)- based quantitative membrane proteomic method was employed to search for components downstream of PHO2. A total of 7491 proteins were identified from Arabidopsis thaliana roots by mass spectrometry, 35.2% of which were predicted to contain at least one transmembrane helix. Among the quantifiable proteins, five were significantly differentially expressed between the wild type and pho2 mutant under two growth conditions. Using immunoblot analysis, we validated the upregulation of several members in PHOSPHATE TRANSPORTER1 (PHT1) family and PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 (PHF1) in pho2 and demonstrated that PHO2 mediates the degradation of PHT1 proteins. Genetic evidence that loss of PHF1 or PHT1;1 alleviated Pi toxicity in pho2 further suggests that they play roles as downstream components of PHO2. Moreover, we showed that PHO2 interacts with PHT1s in the postendoplasmic reticulum compartments and mediates the ubiquitination of endomembrane-localized PHT1;1. This study not only uncovers a mechanism by which PHO2 modulates Pi acquisition by regulating the abundance of PHT1s in the secretory pathway destined for plasma membranes, but also provides a database of the membrane proteome that will be widely applicable in root biology research.
The distinction between different separate primary lung cancers (SPLCs) and intrapulmonary metastases (IPMs) is a challenging but clinically significant issue. Histopathology-based classification is ...the current practice; however, it is subjective and affected by interobserver variability. Recently, next-generation sequencing (NGS) panels have been used in lung cancer diagnostics. This study aimed to investigate the value of large-scale NGS panels for distinguishing between SPLCs and IPMs. A total of 32 patients with 69 lung adenocarcinomas were included. Comprehensive histopathologic assessments of multiple pulmonary adenocarcinomas were performed independently by 3 pathologists. The consensus of histopathologic classification was determined by a majority vote. Genomic analysis was performed using an amplicon-based large-scale NGS panel, targeting single-nucleotide variants and short insertions and deletions in 409 genes. Tumor pairs were classified as SPLCs or IPMs according to a predefined molecular classification algorithm. Using NGS and our molecular classification algorithm, 97.6% of the tumor pairs can be unambiguously classified as SPLCs or IPMs. The molecular classification was predictive of postoperative clinical outcomes in terms of overall survival (P = .015) and recurrence-free interval (P = .0012). There was a moderate interobserver agreement regarding histopathologic classification (κ = 0.524 at the tumor pair level). The concordance between histopathologic and molecular classification was 100% in cases where pathologists reached a complete agreement but only 53.3% where they did not. This study showed that large-scale NGS panels are a powerful modality that can help distinguish SPLCs from IPMs in patients with multiple lung adenocarcinomas and objectively provide accurate risk stratification.
Phytoplasma SAP11 effectors acquired fundamental activity in destabilizing TB/CYC-TCPs, the key factors controlling axillary meristem development, and serve as core virulence factors responsible for ...the witches' broom symptom.
Abstract
As key mediators linking developmental processes with plant immunity, TCP (TEOSINTE-BRANCHED, CYCLOIDEA, PROLIFERATION FACTOR 1 and 2) transcription factors have been increasingly shown to be targets of pathogenic effectors. We report here that TB/CYC (TEOSINTE-BRANCHED/CYCLOIDEA)-TCPs are destabilized by phytoplasma SAP11 effectors, leading to the proliferation of axillary meristems. Although a high degree of sequence diversity was observed among putative SAP11 effectors identified from evolutionarily distinct clusters of phytoplasmas, these effectors acquired fundamental activity in destabilizing TB/CYC-TCPs. In addition, we demonstrate that miR156/SPLs and miR172/AP2 modules, which represent key regulatory hubs involved in plant phase transition, were modulated by Aster Yellows phytoplasma strain Witches' Broom (AY-WB) protein SAP11. A late-flowering phenotype with significant changes in the expression of flowering-related genes was observed in transgenic Arabidopsis plants expressing SAP11AYWB. These morphological and molecular alterations were correlated with the ability of SAP11 effectors to destabilize CIN (CINCINNATA)-TCPs. Although not all putative SAP11 effectors display broad-spectrum activities in modulating morphological and physiological changes in host plants, they serve as core virulence factors responsible for the witches' broom symptom caused by phytoplasmas.
The Skeletal Oncology Research Group machine-learning algorithms (SORG-MLAs) estimate 90-day and 1-year survival in patients with long-bone metastases undergoing surgical treatment and have ...demonstrated good discriminatory ability on internal validation. However, the performance of a prediction model could potentially vary by race or region, and the SORG-MLA must be externally validated in an Asian cohort. Furthermore, the authors of the original developmental study did not consider the Eastern Cooperative Oncology Group (ECOG) performance status, a survival prognosticator repeatedly validated in other studies, in their algorithms because of missing data.
(1) Is the SORG-MLA generalizable to Taiwanese patients for predicting 90-day and 1-year mortality? (2) Is the ECOG score an independent factor associated with 90-day and 1-year mortality while controlling for SORG-MLA predictions?
All 356 patients who underwent surgery for long-bone metastases between 2014 and 2019 at one tertiary care center in Taiwan were included. Ninety-eight percent (349 of 356) of patients were of Han Chinese descent. The median (range) patient age was 61 years (25 to 95), 52% (184 of 356) were women, and the median BMI was 23 kg/m2 (13 to 39 kg/m2). The most common primary tumors were lung cancer (33% 116 of 356) and breast cancer (16% 58 of 356). Fifty-five percent (195 of 356) of patients presented with a complete pathologic fracture. Intramedullary nailing was the most commonly performed type of surgery (59% 210 of 356), followed by plate screw fixation (23% 81 of 356) and endoprosthetic reconstruction (18% 65 of 356). Six patients were lost to follow-up within 90 days; 30 were lost to follow-up within 1 year. Eighty-five percent (301 of 356) of patients were followed until death or for at least 2 years. Survival was 82% (287 of 350) at 90 days and 49% (159 of 326) at 1 year. The model's performance metrics included discrimination (concordance index c-index), calibration (intercept and slope), and Brier score. In general, a c-index of 0.5 indicates random guess and a c-index of 0.8 denotes excellent discrimination. Calibration refers to the agreement between the predicted outcomes and the actual outcomes, with a perfect calibration having an intercept of 0 and a slope of 1. The Brier score of a prediction model must be compared with and ideally should be smaller than the score of the null model. A decision curve analysis was then performed for the 90-day and 1-year prediction models to evaluate their net benefit across a range of different threshold probabilities. A multivariate logistic regression analysis was used to evaluate whether the ECOG score was an independent prognosticator while controlling for the SORG-MLA's predictions. We did not perform retraining/recalibration because we were not trying to update the SORG-MLA algorithm in this study.
The SORG-MLA had good discriminatory ability at both timepoints, with a c-index of 0.80 (95% confidence interval 0.74 to 0.86) for 90-day survival prediction and a c-index of 0.84 (95% CI 0.80 to 0.89) for 1-year survival prediction. However, the calibration analysis showed that the SORG-MLAs tended to underestimate Taiwanese patients' survival (90-day survival prediction: calibration intercept 0.78 95% CI 0.46 to 1.10, calibration slope 0.74 95% CI 0.53 to 0.96; 1-year survival prediction: calibration intercept 0.75 95% CI 0.49 to 1.00, calibration slope 1.22 95% CI 0.95 to 1.49). The Brier score of the 90-day and 1-year SORG-MLA prediction models was lower than their respective null model (0.12 versus 0.16 for 90-day prediction; 0.16 versus 0.25 for 1-year prediction), indicating good overall performance of SORG-MLAs at these two timepoints. Decision curve analysis showed SORG-MLAs provided net benefits when threshold probabilities ranged from 0.40 to 0.95 for 90-day survival prediction and from 0.15 to 1.0 for 1-year prediction. The ECOG score was an independent factor associated with 90-day mortality (odds ratio 1.94 95% CI 1.01 to 3.73) but not 1-year mortality (OR 1.07 95% CI 0.53 to 2.17) after controlling for SORG-MLA predictions for 90-day and 1-year survival, respectively.
SORG-MLAs retained good discriminatory ability in Taiwanese patients with long-bone metastases, although their actual survival time was slightly underestimated. More international validation and incremental value studies that address factors such as the ECOG score are warranted to refine the algorithms, which can be freely accessed online at https://sorg-apps.shinyapps.io/extremitymetssurvival/.
Level III, therapeutic study.
Micronodular thymoma with lymphoid stroma is a rare thymic neoplasm characterized by discrete nodules of epithelial tumor cells separated by abundant lymphoid stroma. The genetic features of ...micronodular thymoma with lymphoid stroma remain largely unexplored. Owing to the interference of abundant intratumoral, nonneoplastic lymphoid cells, a highly sensitive approach is necessary to study genetic changes in these tumors. In this study, we used a highly sensitive next-generation sequencing assay using the molecular barcoding Ion AmpliSeq HD technology to study the most commonly mutated genes in thymomas, including GTF2I, HRAS, NRAS, KRAS, and TP53. A total of 12 cases of micronodular thymomas with lymphoid stroma were tested, and 2 cases also had areas of type A thymoma in their tumor bed. Two micronodular thymic carcinomas with lymphoid stroma, a histological mimic of micronodular thymoma, were also included for comparison. Recurrent p.L424H mutations in GTF2I were found in all the cases of micronodular thymoma with lymphoid stroma but not in the cases of micronodular thymic carcinomas. In addition, 3 cases of micronodular thymoma with lymphoid stroma also had concomitant HRAS and/or KRAS mutations. Our study showed that p.L424H mutations in GTF2I is a constant genetic feature of micronodular thymoma with lymphoid stroma. This finding strongly suggests that micronodular thymoma with lymphoid stroma is closely related to type A and AB thymomas because they all share p.L424H mutations in GTF2I.
Sclerosing pneumocytoma is a rare and distinct lung neoplasm whose histogenesis and molecular alterations are the subject of ongoing research. Our recent study revealed that AKT1 internal tandem ...duplications (ITD), point mutations, and short indels were present in almost all tested sclerosing pneumocytomas, suggesting that AKT1 mutations are a major driving oncogenic event in this tumor. Although the pathogenic role of AKT1 point mutations is well established, the significance of AKT1 ITD in oncogenesis remains largely unexplored. We conducted comprehensive genomic and transcriptomic analyses of sclerosing pneumocytoma to address this knowledge gap. RNA-sequencing data from 23 tumors and whole-exome sequencing data from 44 tumors were used to obtain insights into their genetic and transcriptomic profiles. Our analysis revealed a high degree of genetic and transcriptomic similarity between tumors carrying AKT1 ITD and those with AKT1 point mutations. Mutational signature analysis revealed COSMIC signatures 1 and 5 as the prevailing signatures of sclerosing pneumocytoma, associated with the spontaneous deamination of 5-methylcytosine and an unknown etiology, respectively. RNA-sequencing data analysis revealed that the sclerosing pneumocytoma gene expression profile is characterized by activation of the PI3K/AKT/mTOR pathway, which exhibits significant similarity between tumors harboring AKT1 ITD and those with AKT1 point mutations. Notably, an upregulation of SOX9, a transcription factor known for its involvement in fetal lung development, was observed in sclerosing pneumocytoma. Specifically, SOX9 expression was prominent in the round cell component, whereas it was relatively lower in the surface cell component of the tumor. To the best of our knowledge, this is the first comprehensive investigation of the genomic and transcriptomic characteristics of sclerosing pneumocytoma. Results of the present study provide insights into the molecular attributes of sclerosing pneumocytoma and a basis for future studies of this enigmatic tumor.
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