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Idiopathic pulmonary fibrosis (IPF) is marked with the replacement of normal alveolar tissue by thicker and harder fibrous material, damaged exchange ability. Currently, nintedanib and pirfenidone, are the only FDA-approved drugs with limited efficacy for IPF, which indicated an urgent need to explore new therapies. Disulfiram (DSF), an acetaldehyde dehydrogenase inhibitor, used as anti-alcohol treatment. Despite reported with anti-hepatic fibrosis effect of DSF, the underlying mechanism remains unclear. In our study, DSF exhibited regulative impact on abnormal proliferation, EMT and ECM production in cell models of IPF including primary DHLF-IPF cells and TGF-β1-stimulated A549 cells. The absence of COX-2 was restored by DSF treatment, together with elevated prostaglandin biosynthesis both in vitro and in vivo models of IPF. Furthermore, the anti-fibrotic effect of DSF was impeded with COX-2 knockdown or pharmacological inhibition in TGF-β1-stimulated A549 cells, however, exogenous PGE2 reclaimed with anti-EMT function. In established animal model of IPF, DSF ameliorated declined lung function and histopathological changes, and restrained the lung hydroxyproline content. Together, these findings suggest that the anti-fibrotic effect of DSF was achieved through re-activation of COX-2 mediated PGE2 biosynthesis. The above results suggest that DSF can be applied therapeutically in fibrotic conditions.

Recent advances in the development of surface plasmons (SPs) enhanced LED have provided a great opportunity to enhance either the internal quantum efficiency (IQE) or the spontaneous emission rate (SE) by employing specific metal structures. However, it is still challenging to simultaneously achieve high IQE and Purcell factor (Fp), which demonstrates the SE enhancement, without sacrificing the electrical performance of LEDs. Herein, we designed and investigated a conic metal structure applied to LEDs by comprehensively considering the electrical, optical, and data transmission performance of devices. Conic structures with various heights were implemented to investigate the variation trends of IQE and Fp with the structure design, accompanied by the planar structures as references. A more than five times increase in IQE and almost five times increase in Fp were demonstrated experimentally even with a coupling distance of 100 nm, by employing this conic structure. The theoretical analysis was verified by the experimental results and revealed the mechanism of high Fp and IQE toward high SP–photon coupling efficiency and initial IQE. This study provides a universal strategy to enhance the performance of luminous efficiency and modulation speed of LEDs without sacrificing electrical properties, making them viable for the integration of lighting, display, and communication.

It has been demonstrated in previous studies that lncPART1 is dysregulated in non-small cell lung cancer (NSCLC). However, the function of lncPART1 in NSCLC is unclear. Therefore, this experimental design was based on LncPART1 to explore the pathogenesis of NSCLC. Real-time polymerase chain reaction was used to detect the expression of lncPART1 and miR-17-5p in NSCLC. Cell Counting Kit -8, colony formation, and transwell assays were used to examine the effects of lncPART1 and miR-17-5p on NSCLC cell proliferation and migration invasiveness. Target gene prediction, luciferase reporter assays were used to validate downstream target genes for lncPART1 and miR-17-5p. Western blot analysis was used to detect the expression of TGFBETAR2. LncPART1 was highly expressed in NSCLC. LncPART1 significantly promoted cell proliferation of NSCLC cells. miR-17-5p was down-expressed in NSCLC. miR-17-5p overexpression inhibited cell proliferation and migration invasion in NSCLC cells. LncPART1 was able to inhibit miR-17-5p expression and upregulate the expression level of TGFBETAR2. The results of in vivo animal models confirmed that lncPART1 promoted NSCLC progression by miR-17-5p/TGFBETAR2 axis. LncPART1 promoted the progression of NSCLC by miR-17-5p/TGFBETAR2 axis.

Background and Purpose：As important components of lung tissue, endothelial cells (ECs) are associated with many lung diseases. The role of ECs dysfunction in idiopathic pulmonary fibrosis (IPF) and how to improve alveolar capillary barrier (ACB) to treat IPF is incompletely understood. Therefore we investigated the involvment of endothelial Sphingosine-1-phosphate receptor 1 (S1pr1) in PF and therapeutic effect of selective S1pr1 agonist IMMH002. Experimental approach：Databases of IPF patients and individuals without fibrosis were mined by Seurat. We generated an endothelial-conditional S1pr1 knockout (S1pr1+/−) mice and we also examined a bleomycin-induced model of pulmonary fibrosis (PF). We performed qRT-PCR,Western blot, Immunofluorescence staining and EC permeability experiments. Key results：Expression of S1pr1 in ECs was reduced markedly in IPF patients. Mice with endothelial-specific S1pr1 deficiency exhibited severer inflammation and fibrosis upon challenge with bleomycin. Significant accumulation of alpha-smooth muscle actin (α-SMA) was observed near vessels after S1pr1 deficiency, which indicated a potential connection between ACB injury and fibrosis. S1pr1 activation by a selective agonist IMMH002 could ameliorate PF by improving tight junctions in ECs and protects the ACB. Conclusion and Implications: Our results suggest that S1pr1 plays a significant role in ACB and it could be a potential target for IPF. Activation of S1pr1 with IMMH002 elicits a potent therapeutic effect in bleomycin-induced fibrosis by increasing tight junctions in endothelial cells and protecting the integrity of ACB therefore improve survial rate and lung function.

Background The management of ground‐glass opacities (GGOs) depends mainly on personal experience. In clinical practice, benign GGOs are not rare in resected specimens, for which operations may be avoided. We retrospectively compared the clinical features of resected GGOs to identify differential diagnostic characteristics. Methods Among 1456 patients with suspected malignant GGOs who underwent surgical resection, 105 patients (35 with benign GGOs and 70 matched controls with malignant GGOs) were included. Clinical characteristics, including demographics and radiologic, surgical and pathologic characteristics, were collected. Results The smoking index (P = 0.044), frequency of coughing (P = 0.026), GGO size (P = 0.003), size change during follow‐up (P = 0.011), location (P = 0.022), presence of air bronchogram sign (P = 0.004), distance to the pleura (P = 0.021) and positron emission tomography/computed tomography (PET/CT) appearance (P = 0.003) showed significant differences between the benign and malignant groups. Pathologically, the resected benign GGOs included focal fibrosis (17), inflammation or infection (seven), lymphoproliferative disorder (one), hamartoma (three), inflammatory myofibroblastic tumor (two), hemangioma or vascular malformation (two), endometriosis (two) and pulmonary cyst (one). Conclusions A higher smoking index, coughing, larger size, similar or increased size during follow‐up, location in the upper and middle lobes, air bronchogram sign on CT, lesion margin to pleura distance over 1 cm, and malignant tendency on PET/CT reports were associated with malignant GGOs. Relatively active surgical interventions could be considered for GGOs highly suspected of malignancy., A total of 105 patients (35 cases with benign GGOs and 70 matched controls with malignant GGOs) were enrolled to identify characteristics that would help the differential diagnosis. It is shown that a higher smoking index, cough, larger size, similar or increased size during follow‐up, location in the upper and middle lobes, air bronchogram sign on CT, lesion margin to pleura distance over 1 cm, and malignant tendency on PET/CT reports are associated with malignancy. Pathological patterns of benign GGOs are also provided.

NSCLC is the most common type of lung cancers. The purpose of this study is to screen cancer-related mutations in early LUAD in China through NGS technology, determine their correlation with clinical characteristics and provide basis for treatment decisions. In this study, we performed a 583 gene panel to detect the mutational spectrum of the tumors which were collected from 98 LUAD patients. The sequencing data and clinical characteristics were analyzed. Mutations were identified in 94.9% of patients. EGFR had the highest mutation frequency which was detected in 66% of the patients and was significantly associated with female gender and non-smoking history. Other genes with high mutation frequency were TP53 (37%), ERBB2 (24%), BCOR (22%), ZFHX3 (19%), BTG1 (17%), ATR (16%), WWTR1 (15%), etc. TP53 mutations were significantly associated with medium and low differentiation of tumors; BCOR and BLM mutations with gender; WWTR1 mutations with age; and ATR mutations with visceral pleura invasion were observed. 61% of the patients harbored at less one actionable alteration associated with FDA-recognized or investigational drugs. Multiple mutations in LUAD patients in this study have not previously been reported in NSCLC. Moreover, mutations in driver genes including EGFR, TP53, BCOR, BLM, WWTR1, and ATR were significantly related to clinical features. The panel used in this study is an effective approach for molecular analysis and can be applied in personalized treatment decision-making and drug development.

We have fabricated a tubular whispering gallery mode laser based on InGaN/GaN quantum wells and transferred it onto a flexible substrate. Compared with those without the transferring processes, the threshold energy density was reduced by 60%, at about 25.55 µJ/cm2, while a high-quality factor of &gt, 15,000 was obtained. Finite-difference time-domain simulation demonstrated that such a low threshold energy density can be attributed to the decreased mode volume, from 1.32 × 10−3 μm3 to 6.92 × 10−4 μm3. The wavelength dependences on strain were found to be 5.83 nm, 1.38 nm, and 2.39 nm per stretching unit ε in the X, Y, and Z directions, respectively. Such strain sensitivity was attributed to the deformation of the GaN microtube and the change in the refractive index of the PDMS.

We investigated the excitation-dependent spatially resolved luminescence properties of InGaN/GaN light-emitting diodes (LEDs) with air-cavity arrays using scanning near-field optical microscopy (SNOM), and quantified the effect of the air-cavity structure on the spatial distributions of light-extraction efficiency, internal quantum efficiency, and external quantum efficiency through experiments and numerical simulations. We found that higher light-extraction efficiency and less stress were always observed in the air-cavity areas. Compared to flat areas, the average light-extraction efficiency of the air-cavity areas was improved by 65%, and the residual stress of the air-cavity center was reduced by 89 MPa, which resulted in increased PL intensity, reduced wavelength shift, and narrowed full width at half maximum. The highest external quantum efficiency and aggravated efficiency droop were found in the air-cavity center. At 3.1 W/cm2, the external quantum efficiency and internal quantum efficiency of the air-cavity center were enhanced by 255% and 223%, respectively.

Background Early-stage lung cancers radiologically manifested as ground-glass opacities (GGOs) have been increasingly identified, among which pure GGO (pGGO) has a good prognosis after local resection. However, the optimal surgical margin is still under debate. Precancerous lesions exist in tumor-adjacent tissues beyond the histological margin. However, potential precancerous epigenetic variation patterns beyond the histological margin of pGGO are yet to be discovered and described. Results A genome-wide high-resolution DNA methylation analysis was performed on samples collected from 15 pGGO at tumor core (TC), tumor edge (TE), para-tumor tissues at the 5 mm, 10 mm, 15 mm, 20 mm beyond the tumor, and peripheral normal (PN) tissue. TC and TE were tested with the same genetic alterations, which were also observed in histologically normal tissue at 5 mm in two patients with lower mutation allele frequency. According to the difference of methylation profiles between PN samples, 2284 methylation haplotype blocks (MHBs), 1657 differentially methylated CpG sites (DMCs), and 713 differentially methylated regions (DMRs) were identified using reduced representation bisulfite sequencing (RRBS). Two different patterns of methylation markers were observed: Steep (S) markers sharply changed at 5 mm beyond the histological margin, and Gradual (G) markers changed gradually from TC to PN. S markers composed 86.2% of the tumor-related methylation markers, and G markers composed the other 13.8%. S-marker-associated genes enriched in GO terms that were related to the hallmarks of cancer, and G-markers-associated genes enriched in pathways of stem cell pluripotency and transcriptional misregulation in cancer. Significant difference in DNA methylation score was observed between peripheral normal tissue and tumor-adjacent tissues 5 mm further from the histological margin (p p > 0.05 in all markers). Conclusions According to the methylation pattern observed in our study, it was implied that methylation alterations were not significantly different between tissues at or beyond P10 and distal normal tissues. This finding explained for the excellent prognosis from radical resections with surgical margins of more than 15 mm. The inclusion of epigenetic characteristics into surgical margin analysis may yield a more sensitive and accurate assessment of remnant cancerous and precancerous cells in the surgical margins.

A 3D ITO nanowire network with high quality by using polystyrene as an assisted material has been prepared, demonstrating superior optoelectronic performances with a sheet resistance of 193 Ω/sq at 96% transmission. Both remarkable flexibility tested under bending stress and excellent adhesion applied on special terrain substrate have been achieved. This method has led to a full coverage of micro-holes at a depth of 18 µm and a bottom spacing of only 1 µm, as well as a perfect gap-free coverage for micro-tubes and pyramid array. It has been proved that this 3D ITO nanowire network can be used as a transparent conductive layer for optoelectronic devices with any topography surface. Through the application on the micro-holes, -tubes and -pyramid array, some new characteristics of the 3D ITO nanowires in solar cells, sensors, micro-lasers and flexible LEDs have been found. Such 3D ITO nanowire networks could be fabricated directly on micro-irregular substrates, which will greatly promote the application of the heterotypic devices.

BackgroundPulmonary large-cell neuroendocrine carcinoma (pLCNEC) is a very rare malignancy originating from the lung and bronchus, and its biological behaviour, clinical diagnosis, treatment and prognosis are poorly understood. Thus, the clinical characteristics and surgical treatment-related prognostic factors of this rare disorder must be explored.ResultsThe clinical data of 59 patients (48 males and 11 females) who were treated by surgery and diagnosed with pLCNEC by postoperative pathology at Peking Union Medical College Hospital from April 2004 to April 2019 were analysed retrospectively. The median patient age was 62 years (38–79 years), and the median duration of disease was 2 months (0.5–18 months). Compared with other lung malignancies, pLCNEC lacks specific clinical symptoms and imaging features, and preoperative biopsy pathology is often insufficient to confirm the diagnosis. The corresponding numbers of patients who were classified into stages I, II, III and IV according to the postoperative pathological tumour-nodal-metastasis stage were 25, 12, 15 and 7, respectively. The median overall survival was 36 months (0.9–61.1 months). The 1-year, 3-year and 5-year survival rates were 76.3%, 49% and 44.7%, respectively. The tumour stage exerted a significant effect on survival (Cox multivariate analysis p ConclusionsFor patients with resectable pLCNEC, multidisciplinary therapy based on surgery may have good survival benefits, and tumour stage is an independent risk factor for the prognosis of pLCNEC.

We design, fabricate and analyze plasmon-enhanced LEDs with the tapered Ag structure that significantly increases plasmonic coupling efficiency at a coupling distance far beyond the penetration depth. The electroluminescence intensity showed a 16-fold increase compared with planar LEDs with a coupling distance of 100 nm. The enhanced coupling efficiency with large distance is originated from the accumulated SP energy at the metal conical tip and the missing momentum provided by the corrugated surface. Therefore, the SP-enhanced LED with tapered Ag structure can maintain a high luminous efficiency and a stable working state even with thick p-GaN layer, which also guarantees a high electrical performance. Our study paves the way for a practical implementation of SP-enhanced LEDs with excellent optical and electrical properties.

Background: Our current study was performed with an attempt to detect the expression of microRNA-22-3p (miR-22-3p) in lung adenocarcinoma, as well as to analyze its role in clinical practice. In addition, its relationship with vascular endothelial growth factor (VEGF) and metastasis related indexes was focused. Material and Method: The trials in which 62 cases of lung adenocarcinoma were received to collect tumor tissue (study group) and normal lung tissue (control group) were eligible for this study. The expression of miR-22-3p in the two groups was detected through RT-PCR. Immunohistochemical method was used to detect the expression of VEGF and leukocyte differentiation antigen 31 (CD31) marked microvessel density (MVD) in lung adenocarcinoma. The expressions of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-7 (MMP-7) in lung adenocarcinoma were also detected through the use of Western Blot. Results: The present study revealed significant difference in the expression of miR-22-3p between the two groups. No significant difference in the expression of gender, age, neural invasion and the number of lesions were observed between groups. There was significant difference in the expression of miR-22-3p in the maximum diameter of tumor, pleural recidivism, vascular recidivism, lymph node metastasis and different TNM stages. Based on survival analysis, miR-22-3p was linked to survival time. Correlation analysis indicated that there was negative correlation between miR-22-3p and VEGF, miR-22-3p and MVD, miR-22-3p and MMP-3, and miR-22-3p and MMP-7 in lung adenocarcinoma. Conclusion: Our findings provide evidence that miR-22-3p is low expressed in lung adenocarcinoma tissues and the low expression of miR-22-3p is closely associated with clinicopathological characteristics and the prognosis. MiR-22-3p may be involved in the tumor progression of lung adenocarcinoma and may serve as a biomarker for the diagnosis and prognosis of lung adenocarcinoma.

Lung cancer is the deadliest type of cancer worldwide and late detection is the major factor for the low survival rate of patients. Low dose computed tomography has been suggested as a potential screening tool but manual screening is costly and time-consuming. This has fuelled the development of automatic methods for the detection, segmentation and characterisation of pulmonary nodules. In spite of promising results, the application of automatic methods to clinical routine is not straightforward and only a limited number of studies have addressed the problem in a holistic way. With the goal of advancing the state of the art, the Lung Nodule Database (LNDb) Challenge on automatic lung cancer patient management was organized. The LNDb Challenge addressed lung nodule detection, segmentation and characterization as well as prediction of patient follow-up according to the 2017 Fleischner society pulmonary nodule guidelines. 294 CT scans were thus collected retrospectively at the Centro Hospitalar e Universitrio de So Joo in Porto, Portugal and each CT was annotated by at least one radiologist. Annotations comprised nodule centroids, segmentations and subjective characterization. 58 CTs and the corresponding annotations were withheld as a separate test set. A total of 947 users registered for the challenge and 11 successful submissions for at least one of the sub-challenges were received. For patient follow-up prediction, a maximum quadratic weighted Cohen's kappa of 0.580 was obtained. In terms of nodule detection, a sensitivity below 0.4 (and 0.7) at 1 false positive per scan was obtained for nodules identified by at least one (and two) radiologist(s). For nodule segmentation, a maximum Jaccard score of 0.567 was obtained, surpassing the interobserver variability. In terms of nodule texture characterization, a maximum quadratic weighted Cohen's kappa of 0.733 was obtained, with part solid nodules being particularly challenging to classify correctly. Detailed analysis of the proposed methods and the differences in performance allow to identify the major challenges remaining and future directions - data collection, augmentation/generation and evaluation of under-represented classes, the incorporation of scan-level information for better decision-making and the development of tools and challenges with clinical-oriented goals. The LNDb Challenge and associated data remain publicly available so that future methods can be tested and benchmarked, promoting the development of new algorithms in lung cancer medical image analysis and patient follow-up recommendation.

Background: Small-cell lung cancer (SCLC) patients are generally not considered to be candidates for surgical intervention. The role of surgery in the multidisciplinary treatment of SCLC remains controversial. The study aims to summarize and analyse the clinical characteristics and prognosis of SCLC patients after surgical treatment and identify the related prognostic factors.Methods: The clinical data of 130 SCLC patients (99 males and 31 females) who were treated by surgery and confirmed by postoperative pathological examination in Peking Union Medical College Hospital from April 2004 to April 2019 were analysed retrospectively.Results: The median age was 60 years (30-83 years), and the median disease duration was 2 months (0.5-48 months). The patients did not have specific clinical or imaging manifestations. Postoperative pathological examination revealed that 36 patients had stage I, 22 patients had stage II, 65 patients had stage III, and seven patients had stage IV SCLC. The median overall survival time was 50 months (95% confidence interval, 10.8-89.2 months). The median survival time of stage I, II, III, and IV SCLC patients were 148 months, 42 months, 32 months, and 10 months, respectively. In patients who underwent surgical treatment, postoperative adjuvant therapy and tumour stage were two significant influencing factors of survival (Cox multivariate analysis P < 0.05).Conclusions: Surgical treatment combined with adjuvant therapy can achieve satisfactory outcomes in selected SCLC patients. Adjuvant therapy and tumour stage are independent risk factors. Surgical treatment is indicated in SCLC patients preoperatively staged as I-IIIa, and anatomical lobectomy and lymphadenectomy combined with postoperative adjuvant therapy are recommended.

Indium tin oxide (ITO) materials with different morphologies have been fabricated via sputtering technology by adjusting the oxygen flow rate and RF-power. The repeatable and controllable growth conditions of different ITO materials have been achieved. The gas sensors with different ITO materials were fabricated on ceramic tube directly, which have the characteristics of low cost and simple preparation process. Through our analysis, the nanowires have larger specific surface area, more oxygen vacancies and an oriented electron transport channel. The sensor made by nanowires was the best one, and the value of sensitivity run up to 235.6 at the ethanol gas concentration of 400 ppm under 250 °C.The gas sensing properties of the whole ITO material system to ethanol gas were studied. The difference of gas sensing properties is explained by calculating the surface adsorption energy of ITO materials with different morphologies based on first-principle calculation method. These results provide guidance for the application of ITO materials in the field of gas sensors.

Lung cancer is the leading cause of cancer-related death. Early stage lung cancer detection using computed tomography (CT) could prevent patient death effectively. However, millions of CT scans will have to be analyzed thoroughly worldwide, which represents an enormous burden for radiologists. Therefore, there is significant interest in the development of computer algorithms to optimize this clinical process.

BAlN is a promising ultrawide bandgap semiconductor, but systematic studies of its bandgap are scarce. Here, bandgap engineering of BAlN containing the phase transition factor (from hexagonal to wurtzite structures) has been investigated by DFT calculations and verified experimentally. The calculated bandgap bowing parameter of hexagonal BAlN (h-BAlN) is 2.29 eV, while the bandgap bowing parameters of wurtzite BAlN (w-BAlN) are −4.09 eV and 2.48 eV in the B-rich and Al-rich regions, respectively. Meanwhile, calculations indicate that BAlN preferentially forms w-BAlN at Al composition above 18.7%. So, the bandgap variation of BAlN is divided into three regions based on Al composition: h-BAlN (0–18.7%), B-rich w-BAlN (18.7%–50%), Al-rich w-BAlN (50%–1), and each has its own trend. Experimentally, h-BAlN and w-BAlN films were prepared by magnetron co-sputtering technique and the phase transition was observed in X-ray diffraction (XRD) patterns. h-BAlN shows a typical triangular morphology and the Raman and XRD peaks are located at 1371 cm−1 and 44.3°, tending to (1 0 1) h-BN. w-BAlN has a “needle-felt” surface with Raman and XRD peaks at 656 cm−1 and 35.9°, tending to (0 0 2) w-AlN. The experimental bandgap variation of BAlN shows a “W” shape, which can be well explained by the calculation results.

The selective area growth (SAG) technique enables the creation of multi-color micro-structures. However, the substrate pattern to obtain multi-color and mass transfer of these micro-structures are complicated to achieve. Moreover, high dislocation density as well as large residual stress in c-plane quantum wells still remain challenges. Here, an improved SAG strategy was proposed to achieve completely merged asymmetric pyramids on closely connected deep-concave holes via the lateral overgrowth of adjacent pyramids. These asymmetric pyramids were directly grown on the sapphire substrate, making mass transfer be possible. Growth rate distinction appears at the different positions of the overgrowth region, resulting in a multi-wavelength emission. More importantly, the residual stress and the dislocation density can be suppressed by utilizing the deep-hole pattern and lateral overgrowth, contributing to a lower piezoelectric polarization field and a higher spontaneous emission rate. These ultrafast and high-efficient multi-color micro-LEDs are suitable for the application in high-resolution display, flexible devices, and high-speed visible-light-communication.

Background: Thymic epithelial tumors (TETs), including thymoma and thymic carcinoma (TC), are one of the rarest cancers. Unlike thymoma, TC is clinically agressive and responds poorly to first-line chemotherapy and second-line systemic therapy. Currently, sunitinib is the only receptor tyrosine kinase inhibitor approved for TC treatment. However, most TC patients do not have the corresponding c-Kit mutations. Because the molecular drivers of TC are almost unknown, characterization of the mutational landscape of TC will broaden our understanding of TC etiology and facilitate the development of effective targeted therapies. Methods: Comprehensive genomic profiling, including SNV, indels, copy number alterations and re-arrangement analysis, was performed with a 830-gene next-generation sequencing panel on tumor tissues from a cohort of 32 TET patients (16 TCs and 16 thymomas). Results: Recurrent mutated genes in this TET cohort were TP53, CYLD, KMT2C, BRCA1, CHD2, PBRM1, ARID2, ASXL1, BRD7, CDKN2A, EGFR, KIT, MYH9, NFKB1A, RB1 and TET2. TP53 is the most frequently mutated gene, seen in 31% (5/16) of TCs and 6% (1/16) of thymomas. We found two actionable mutations in TCs (KIT D579del and IDH1 R132C) and one in thymomas (KIT V560D). Consistent with previous reports, we observed recurrent mutations in multiple genes encoding epigenetic regulator proteins (ASXL1, TET2 KMT2C, CHD2, PBRM1, ARID2 and BRD7), all in TCs but not thymomas. Most importantly, we found four CYLD mutations (two stop gain, one frameshift and one missense) and two NFKBIA mutations (one frameshift and one in splicing-site) in 6 TC samples. Both CYLD and NFKBIA genes encode negative regulators of NF-κB signaling pathway. CYLD is a Ub-specific protease (USP)-type deubiquitinase that preferentially disassembles Lys63-Ub, a post-translational modification required for the activation of NF-κB, while NFKBIA causes trapping REL dimers induced inhibitory activity of dimeric NF-κB/REL protein complexes. Furthermore, genomic alterations in NFKBIA and CYLD were mutually exclusive. Our results indicated that loss-of-function mutations in CYLD and NFKBIA may function as the molecular drivers of TC through constitutive activation of NF-κB signaling pathway. Conclusion: Our findings provide an enhanced road map for the etiology of TC. Further investigation is warranted into the roles of NF-κB pathway and epigenetic regulators dysfunction in TC pathogenesis and their potential for clinical trials. Citation Format: Naixin Liang, Xiaomo Li, Tonghui Ma, Chao Gao, Zhili Cao, Lei Cao, Zhongxing Bing, Zhenhuan Tian, Chao Guo, Shanqing Li, Yadong Wang, Jianchao Xue, Ji Li, Xiaoguang Li, Peng Liu, Shuyang Zhang. Genome profiling of thymic carcinoma identifies putative driver mutations in the NF-κB signaling pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2252.

Additional file 1. Additional data and figures.

Modulation bandwidth and the emission region are essential features for the widespread use of visible light communications (VLC). This paper addresses the contradictory requirements to achieve broadband and proposes ultrafast, asymmetric pyramids grown on adjacent deep concave holes via lateral overgrowth. Multicolor emission with an emission region between 420 nm and 600 nm is obtained by controlling the growth rate at different positions on the same face, which also can provide multiple subcarrier frequency points for the employment of wavelength division multiplexing technology. The spontaneous emission rate distinction is narrowed by lowering the number of the crystal plane, ensuring a high modulation bandwidth over broadband. More importantly, the residual stress and dislocation density were minimized by employing a patterned substrate, and lateral overgrowth resulted in a further enhancement of the recombination rate. Finally, the total modulation bandwidth of multiple subcarriers of the asymmetric pyramids is beyond GHz. These ultrafast, multicolor microLEDs are viable for application in VLC systems and may also enable applications for intelligent lighting and display.

Multimode and random directionalities are major issues restricting the application of whispering gallery mode microcavity lasers. We demonstrated a 40 μm diameter microring with an off-centered embedded hole and warped geometry from strained III-nitride quantum well multilayers. Single-mode directional whispering gallery mode lasing was achieved by the warped structure and high-order mode suppression induced by the off-centered hole. In addition, the introduction of the off-centered hole reduced the lasing threshold from 3.24 to 2.79 MW / cm 2 compared with the warped microdisk without an embedded hole while maintaining a high-quality factor of more than 4000. Directional light emission in 3D was achieved and attributed to the warped structure, which provides a vertical component of the light emission, making it promising for building multifunctional coherent light sources in optoelectronic integration.

A new package structure with three convex phosphor layers is shown to enhance the angular color uniformity based on modeling and experimental verification. The color uniformity has been improved by tailoring the phosphor concentration distribution of the three layers. The experimental measurements indicate that the deviation of angular correlated color temperature (CCT) can be reduced from 152.9, 487.2, and 586.4 K to 51.3, 55.1, and 78.7 K compared with the conventional structure at the average CCT of 4500, 5500, and 6200 K, respectively. Luminous flux and optical output power of LED packages with optimized multilayer phosphor have been measured and are reduced no more than 5% compared with the single phosphor layer packages.

Well-aligned, lateral and vertical oriented nanoporous GaN was fabricated using the electrochemical etching procedure and its influence on the optical characteristics of ultraviolet-A multiple quantum well (MQW) structure was investigated. We used a MQW structure with a V-defect and n-Al0.1Ga0.9 N layer, which greatly improved the uniformity of vertical electrochemical etching. Compared to the as-grown MQW structure, the lateral and vertical oriented nanoporous MQW structures have 3.8-fold and 8.1-fold photoluminescence intensity enhancement and the full width at half maximum has been narrowed from 18.4 nm to 7.9 nm and 2.8 nm, respectively. The vertical oriented nanoporous MQW structure has a rectangular far-field emission pattern with uniform forward light distribution and the view angle of 85% intensity is 50°. This study provides an effective method for improving the light output and controlling the emission angle of GaN based light emitting devices, as well as a method for preparing well-aligned nanopores in semiconductors.

Thermal management is a critical issue for the packaging of light-emitting diodes (LED). With poor thermal management, the elevated junction temperature of the LED chip will result in shorter life, lower efficiency, and color shifting. As a common practice, people typically used the thermal resistance concept for thermal management. However, this highly simplified model is 1-D in nature. The heat spreading in the direction transverse to the main path of heat conduction in the LED package cannot be taken into account. The present study investigated the effect of substrate dimensions and boundary conditions on the transverse heat spreading of a high power LED package. It was found that the conventional concept of thermal resistance may not apply when the thickness of package substrate reaches a certain level. The heat spreading in the transverse direction may exhibit certain unexpected behaviors. In some cases, the trends of junction temperature of LED may be totally opposite to the engineering intuition. Some discussion on the transverse heat spreading effect is given in this paper.

GaN-based 500 nm light-emitting diodes (LEDs) with an air-cavity formed on a laser-drilled hemispherical patterned sapphire substrate (HPSS) were investigated. The cross-section transmission electron microscopy image of the HPSS-LED epilayer indicated that most of the threading dislocations were bent towards the lateral directions. It was found that in InGaN/GaN multiple quantum wells (MQWs) of HPSS-LEDs, there were fewer V-pits and lower surface roughness than those of conventional LEDs which were grown on flat sapphire substrates (FSSs). The high-resolution x-ray diffraction showed that the LED grown on a HPSS has better crystal quality than that grown on a FSS. Compared to FSS-LEDs, the photoluminescence (PL) intensity, the light output power, and the external quantum efficiency at an injected current of 20 mA for the HPSS-LED were enhanced by 81%, 65%, and 62%, respectively, such enhancements can be attributed to better GaN epitaxial quality and higher light extraction. The slightly peak wavelength blueshift of electroluminescence for the HPSS-LED indicated that the quantum confined Stark effect in the InGaN/GaN MQWs has been reduced. Furthermore, it was found that the far-field radiation patterns of the HPSS-LED have smaller view angles than that of the FSS-LED. In addition, the scanning near field optical microscope results revealed that the area above the air-cavity has a larger PL intensity than that without an air-cavity, and the closer to the middle of the air-cavity the stronger the PL intensity. These nano-light distribution findings were in good agreement with the simulation results obtained by the finite difference time domain method.

We demonstrated a method to obtain super flexible LEDs, based on high quality pyramid arrays grown directly on sapphire substrates. Laser lift-off (LLO) and dual transfer processes were applied to transfer pyramid arrays face up onto the flexible substrates, which is more efficient than back light emission. Ag grid and Ag nanowires were employed as the electrical connection. No significant performance reduction appeared until the device reached a curvature radius of 0.5 mm. The performance reduction results from cracks appearing at the junction of the Ag grid, which can be improved by replacing the Ag grid with a strip electrode.

We tried to obtain microstructures on a three-dimensional (3D) micropatterned substrate by laser drilling. The influences of the dimensions of the drilling holes on the morphology and the material quality of the grown structures were studied. Uniform micropyramid arrays with relatively low dislocation density can be achieved by adjusting the laser drilling parameters. The internal quantum efficiency was estimated to be improved by a factor of 3 for a pyramid structure compared with that of planar LEDs. We fabricated 5 × 7 mm2 flexible LEDs employing the pyramid structure and the devices exhibited good flexibility without performance reduction after bending.

This report describes the fabrication and resistive switching (RS) characteristics of a novel flexible transparent (FT) resistive random access memory (ReRAM) device with a Ag/indium–tin oxide (ITO) nanowire network/ITO capacitor deposited on a PDMS substrate. The transmittance of the device is ∼70% in the visible region, and it exhibits a stable high-resistance state (HRS) to low-resistance state (LRS) ratio (HRS/LRS ratio) in different bending states. The RS characteristics are attributed to the congregate state of oxygen vacancies at different voltages, and the difference between positive and negative bending is mainly contributed by the effect of stress on the conductive layer. The FT-ReRAM can be used as nonvolatile memory element in future flexible transparent devices.