Systematic Characterization of the Clinical and Pathological Features of Schwannomas Harboring SH3PXD2A::HTRA1 Fusion.

The understanding of schwannoma tumorigenesis has been reshaped by the recent identification of SH3PXD2A::HTRA1 fusion in 10% of intracranial/spinal schwannomas. Nonetheless, pathologic features of schwannomas harboring this fusion, as well as its prevalence outside intracranial/spinal locations, have not been characterized. We screened 215 consecutive schwannomas for their clinicopathologic characteristics and fusion status using reverse-transcriptase polymerase chain reaction (RT-PCR). Among 29 (13.5%) fusion-positive schwannomas, the most prevalent location was peripheral somatic tissue (30.7%, 19/62), followed by spinal/paraspinal (18.4%, 7/38), body cavity/deep structures (10%, 2/20), intracranial (1.3%, 1/75), and viscera (0/13). All 8 cellular, 4 microcystic/reticular, and 3 epithelioid schwannomas were fusion-negative, as were 41/42 nonschwannomatous peripheral nerve sheath tumors. Remarkably, a distinct 'serpentine' palisading pattern, comprising ovoid/plump cells shorter than usual schwannian cells in a hyalinized stroma, was identified in most fusion-positive cases and the schwannomatous component of the only fusion-positive malignant peripheral nerve sheath tumor. To validate this finding, 60 additional cases were collected, including 36 with (≥10% arbitrarily) and 24 without appreciable serpentine histology, of which 29 (80.6%) and 2 (8.3%) harbored the fusion, respectively. With percentages of 'serpentine' areas scored, 10% was determined as the optimal practical cut-off to predict the fusion status (sensitivity, 0.950; specificity, 0.943). Fusion positivity was significantly associated with serpentine histology, smaller tumors, younger patients, and peripheral somatic tissue, while multivariate logistic linear regression analysis only identified serpentine histology and location as independent fusion-predicting factors. RNA in situ hybridization successfully detected the fusion junction, highly concordant with RT-PCR results. Gene expression profiling on 18 schwannomas demonstrated segregation largely consistent with fusion status. Fusion-positive cases expressed significantly higher HTRA1 mRNA abundance, perhaps exploitable as a biomarker. In summary, we systematically characterize a series of 60 SH3PXD2A::HTRA1 fusion-positive schwannomas, showing their distinctive morphology and location-specific prevalence for the first time.

Extraskeletal Myxoid Chondrosarcomas: The Uncommon Clinicopathologic Manifestations and Significance of TAF15::NR4A3 Fusion.

Extraskeletal myxoid chondrosarcoma (EMC) is an ultrarare sarcoma typically exhibiting myxoid/reticular histology and NR4A3 translocation. However, morphologic variants and the relevance of non-EWSR1::NR4A3 fusions remain underexplored. Three challenging pan-Trk-expressing cases, featuring cellular to solid histology, were subjected to RNA exome sequencing (RES), unveiling different NR4A3-associated fusions. Alongside RES-analyzed cases, fluorescence in situ hybridization was performed to confirm 58 EMCs, with 48 available for pan-Trk immunostaining and KIT sequencing. Except for 1 (2%) NR4A3-rearranged EMC without identifiable partners, 46 (79%), 9 (16%), and 2 (3%) cases harbored EWSR1::NR4A3, TAF15::NR4A3, and TCF12::NR4A3 fusions, respectively. Five EWSR1::NR4A3-positive EMCs occurred in the subcutis (3) and bone (2). Besides 43 classical cases, there were 8 cellular, 4 rhabdoid/anaplastic, 2 solid, and 1 mixed tumor-like variants. Tumor cells were oval/spindle to pleomorphic and formed loose myxoid/reticular to compact sheet-like or fascicular patterns, imparting broad diagnostic considerations. RES showed upregulation of NTRK2/3, KIT, and INSM1. Moderate-to-strong immunoreactivities of pan-Trk, CD117, and INSM1 were present in 35.4%, 52.6%, and 54.6% of EMCs, respectively. KIT p. E554K mutation was detected in 2/48 cases. TAF15::NR4A3 was significantly associated with size >10 cm (78%, P = .025). Size >10 cm, moderate-to-severe nuclear pleomorphism, metastasis at presentation, TAF15::NR4A3 fusion, and the administration of chemotherapy portended shorter univariate disease-specific survival, whereas only size >10 cm (P = .004) and metastasis at presentation (P = .032) remained prognostically independent. Conclusively, EMC may manifest superficial or osseous lesions harboring EWSR1::NR4A3, underrecognized solid or anaplastic histology, and pan-Trk expression, posing tremendous challenges. Most TAF15::NR4A3-positive cases were >10 cm in size, ie, a crucial independent prognosticator, whereas pathogenic KIT mutation rarely occurred.

Polymer entanglement drives formation of fibers from stable liquid bridges of highly viscous dextran solutions.

Liquid bridges have been studied for over 200 years due to their occurrence in many natural and industrial phenomena. Most studies focus on millimeter scale liquid bridges of Newtonian liquids. Here, reptation theory was used to explain the formation of 10 cm long liquid bridges of entangled polymer solutions, which subsequently stabilize into polymer fibers with tunable diameters between 3 and 20 mm. To control the fiber formation process, a horizontal single-fiber contact drawing system was constructed consisting of a motorized stage, a micro-needle, and a liquid filled reservoir. Analyzing the liquid bridge rupture statistics as a function of elongation speed, solution concentration and dextran molecular weight revealed that the fiber formation process was governed by a single timescale attributed to the relaxation of entanglements within the polymer solution. Further characterization revealed that more viscous solutions produced fibers of larger diameters due to secondary flow dynamics. Verification that protein additives such as type I collagen had minimal effect on fiber formation demonstrates the potential application in biomaterial fabrication.

Visible light positioning (VLP) system using low-cost organic photovoltaic cell (OPVC) for low illumination environments.

We propose and demonstrate a received-signal-strength (RSS) based visible light positioning (VLP) system using a low-cost organic photovoltaic cell (OPVC) receiver (Rx). The OPVC is a passive device without the need of external power supply. It could detect VLC signal and harvest energy. Our developed OPVC has a high power conversion efficiency (PCE) of 9.8%. The VLP system can be operated at a low illumination of 130 lux. The regression machine learning (ML) algorithm is used to enhance the positioning accuracy.

The expanding morphological and genetic spectrum of MYOD1-mutant spindle cell/sclerosing rhabdomyosarcomas: a clinicopathological and molecular comparison of mutated and non-mutated cases.

AIMS: Spindle cell/sclerosing rhabdomyosarcomas (SC/SRMS) feature spindled and/or rounded rhabdomyosarcomatous cells within variably hyalinised stroma. Only 30-67% of SC/SRMSs harbour neomorphic MYOD1 p.L122R mutations, indicating heterogeneity in this RMS type. We compared MYOD1-mutant and non-mutant cases to characterise the histological and genetic spectrum of mutated SC/SRMS. METHODS AND RESULTS: Seventeen RMSs with spindled, sclerosing or hybrid histology were sequenced to identify MYOD1 and PIK3CA mutations and reappraised to assess histological features and myogenic immunophenotypes. Twelve SC/SRMSs harboured MYOD1 mutations, including homozygous p.L122R (n = 8), heterozygous p.L122R (n = 3) and heterozygous p.E118K (n = 1). MYOD1-mutant tumours affected nine females and three males aged 8-64 years (median = 22.5), had a median size of 4.2 cm (range = 2-22) and involved the head and neck (n = 7), extremities (n = 4) and mediastinum (n = 1). Fascicular/spindle histology was predominant in four cases, including one with heterologous lipoblasts in focally myxoid stroma. Four sclerosing cases mainly comprised rounded cells, including one with multinucleated tumour cells. Four cases were histologically hybrid. The only PIK3CA (p.H1047R) mutation was detected in a predominantly spindled MYOD1-p.L122R-mutated case, but not in its laser-microdissected lipoblast-containing area. All MYOD1-mutant cases exhibited diffuse MYOD1 expression but patchy myogenin reactivity. At final follow-up (median = 13.5 months), recurrences (n = 4), metastases (n = 2) or both (n = 1) occurred in seven MYOD1-mutant cases; one had died of disease. Five non-mutated cases were reclassified as spindle embryonal (n = 3), dense embryonal (n = 1) and unclassifiable (n = 1) RMSs. CONCLUSION: MYOD1-mutant RMSs are uncommonly mutated with PIK3CA and behave aggressively with an expanded morphological and genetic spectrum, including lipoblastic differentiation, multinucleated cells and the alternative p.E118K mutation.

Ouabain induces apoptotic cell death in human prostate DU 145 cancer cells through DNA damage and TRAIL pathways.

Ouabain, a cardiotonic steroid and specific Na+ /K+ -ATPase inhibitor, has a potential to induce cancer cell apoptosis but the mechanisms of apoptosis induced by ouabain are not fully understand. The aim of this study was to investigate the cytotoxic effects of ouabain on human prostate cancer DU 145 cells in vitro. Cell morphological changes were examined by phase contrast microscopy. Cell viability, cell cycle distribution, cell apoptosis, DNA damage, the production of ROS and Ca2+ , and mitochondrial membrane potential (ΔΨm ) were measured by flow cytometry assay. Results indicated that ouabain induced cell morphological changes, decreased total cell viability, induced G0/G1 phase arrest, DNA damage, and cell apoptosis, increased ROS and Ca2+ production, but decreased the levels of ΔΨm in DU 145 cells. Ouabain also increased the activities of caspase-3, -8, and -9. Western blotting was used for measuring the alterations of apoptosis-associated protein expressions in DU 145 cells and results indicated that ouabain increased the expression of DNA damage associated proteins (pATMSer1981 , p-H2A.XSer139 , and p-p53Ser15 ) and ER-stress-associated proteins (Grp78, ATF6ß, p-PERKThr981 , PERK, eIF2A, GADD153, CaMKIIß, and caspase-4) in time-dependently. Furthermore, ouabain increased apoptosis-associated proteins (DR4, DR5, Fas, Fas Ligand, and FADD), TRAIL pathway, which related to extrinsic pathway, promoted the pro-apoptotic protein Bax, increased apoptotic-associated proteins, such as cytochrome c, AIF, Endo G, caspase-3, -8, and -9, but reduced anti-apoptotic protein Bcl-2 and Bcl-x in DU 145 cells. In conclusion, we may suggest that ouabain decreased cell viability and induced apoptotic cell death may via caspase-dependent and mitochondria-dependent pathways in human prostate cancer DU 145 cells.

Highly foldable transparent conductive films composed of silver nanowire junctions prepared by chemical metal reduction.

A simple method is demonstrated to improve the folding reliability and sheet resistance of silver nanowire (Ag NW)-based transparent conductive films (TCFs) without overcoated layers or complicated processes. As-coated Ag NW film is immersed in a silver-surrounded solution, in which the silver was reduced by Tollen's reagent. Therefore, the reduced silver can be deposited on the surface and crossing of Ag NWs to form a weld-like junction and bind the Ag NWs together, hence decreasing the contact resistance of Ag NW structure at wire-to-wire junctions by increasing the contact surface area. Compared with original Ag NW TCFs, this Ag NW junction structure not only shows compatibility with conventional wet processes, but also demonstrates outstanding flexibility, even when the entire film is folded. This could be attributed to the robustly weld-like wire-to-wire junction of Ag NWs, which enhances its mechanical characteristics. The results demonstrated the feasibility of this alternative approach for the development of an effective low-power-consumption route for fabricating foldable transparent electrodes. Moreover, the results also indicated the practicability of applying this foldable transparent electrode in the fabrication of highly flexible and wearable optoelectronic devices.

Stromal categorization of recurrent oral cancer after salvage surgery is associated with survival rates.

BACKGROUND: Recurrent oral cancer incurred grave outcome. Tumor microenvironment features, like tumor-infiltrating lymphocytes (TILs) or tumor stromal ratio (TSR) had prognostic significance in various cancers. We aimed to evaluate the impact of stromal categorization which incorporated the stromal TILs and TSR on survival outcomes in recurrent oral cancer. METHODS: 162 patients who received surgery-based treatment between 2010 and 2020 were recruited. Outcomes were 5-year overall survival (OS) and disease-specific survival (DSS). The impact of stromal categorization of recurrent primary tumor or node on 5-year OS and DSS were assessed with the Kaplan-Meier method. Multivariate analysis was performed, incorporating variables at initial treatment and salvage surgery. Patients were further categorized using a survival decision tree. RESULTS: Mean age was 56.1 (SD, 11.3) years; 153 patients (94.4%) were male; 51 patients (31.5%) had stromal category III. Local recurrence occurred in 94 patients (58%), regional recurrence in 55 (34%), and loco-regional recurrence in 13 (8%). Patients with stromal category III had poorer 5-year OS and DSS. Prior radiotherapy, advanced recurrent stage, positive surgical margin, and stromal category III were independent prognosticators for 5-year OS and DSS. In survival decision tree analysis, patients with prior radiotherapy and stromal category III had the worst outcomes. CONCLUSION: Stromal categorization is associated with outcomes in recurrent oral cancer. Patients with poor prognosticators, such as stromal categorization III, prior radiation, and advanced stage may require closer follow-up and intensive treatment.

Incorporation of stromal tumor-infiltrating lymphocytes into an early death prediction model significantly improves net reclassification for outcome estimation in advanced buccal cancer.

We explored the impact of stromal tumor-infiltrating lymphocytes (sTILs) on the prognostic value of an early death model for advanced buccal cancer. We assessed 121 patients with advanced buccal cancer who underwent primary tumor resection at a medical center. Predictors of early death and 5-year overall survival (OS) were analyzed using Cox regression models. Performance of models was evaluated with the Harrell C and Akaike information criterion. The net reclassification improvement of the early death model was also calculated relative to the 5-year OS model for one-year all-cause mortality. A total of 121 patients with advanced buccal cancer were recruited. Mean age was 56.1 ± 9.8 years; 117 (96.7%) patients were male. sTILs ≤30%, clinical nodal disease, pathological nodal disease, poor differentiation, lymphovascular invasion, perineural invasion, WPOI 5, and no adjuvant radiotherapy were risk factors for early death in univariate analysis. In multivariate analysis, clinical TNM, sTILs, clinical nodal disease, poor differentiation, lymphovascular invasion, and no adjuvant RT were independent factors for early death. sTILs, pathological nodal disease, poor differentiation, lymphovascular invasion, and no adjuvant RT were independent factors for early death in the multivariate model with pathological TNM. The discriminatory ability was better for early death model for 1-year all-cause mortality. Finally, incorporation of sTILs into the early death model increased net reclassification by 21% for the clinical TNM model and 28% for the pathological TNM model. Addition of sTILs improved the early death model, which may help physicians to identify high-risk patients for more intensive treatment and follow-up.

Interleukin-8/CXCR1 Signaling Contributes to the Progression of Pulmonary Adenocarcinoma Resulting in Malignant Pleural Effusion.

Pulmonary adenocarcinoma (PADC) treatment limited efficacy in preventing tumor progression, often resulting in malignant pleural effusion (MPE). MPE is filled with various mediators, especially interleukin-8 (IL-8). However, the role of IL-8 and its signaling mechanism within the fluid microenvironment (FME) implicated in tumor progression warrants further investigation. Primary cultured cells from samples of patients with MPE from PADC, along with a commonly utilized lung cancer cell line, were employed to examine the role of IL-8 and its receptor, CXCR1, through comparative analysis. Our study primarily assessed migration and invasion capabilities, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties. Additionally, IL-8 levels in MPE fluid versus serum, along with immunohistochemical expression of IL-8/CXCR1 signaling in tumor tissue and cell blocks were analyzed. IL-8/CXCR1 overexpression enhanced EMT and CSC properties. Furthermore, the immunocytochemical examination of 17 cell blocks from patients with PADC and MPE corroborated the significant correlation between upregulated IL-8 and CXCR1 expression and the co-expression of IL-8 and CXCR1 in MPE with distant metastasis. In summary, the IL-8/ CXCR1 axis in FME is pivotal to tumor promotion via paracrine and autocrine signaling. Our study provides a therapeutic avenue for improving the prognosis of PADC patients with MPE.

C-kit expression of melanocytic neoplasm and association with clinicopathological parameters and anatomic locations in Chinese people.

Distinct genetic aberrations between melanomas in different anatomical locations have been confirmed in recent years. However, the associations between immunohistochemical expression, tumor sites, and clinical parameters are not clear. We examined the correlation of protein expression and gene mutation of c-kit with clinicopathological parameters and lesion locations in patients with malignant melanoma (MM). We collected 170 melanocytic lesions, including 106 cutaneous MM from acral melanoma (AM) and nonacral melanoma (NAM) sites, 24 dysplastic nevi, and 40 common melanocytic nevi. Tissue microarray was constructed, and immunohistochemical expression for c-kit was assessed with correlation with clinical parameters. Mutation in exons 11, 13, 17, and 18 of KIT gene in genomic DNA by polymerase chain reaction sequencing was also analyzed. Immunostaining scores for c-kit were found to be statistically higher in Dysplastic Nevi than in common melanocytic nevi and MM. In addition, cytoplasmic c-kit staining was significantly correlated with poor survival in patients with AM but not in those with NAM. Twenty-nine cases of MM (including 9 NAM and 20 AM) are analyzed for mutation in exons 11, 13, 17, and 18 of KIT gene in genomic DNA by polymerase chain reaction sequencing, and no genetic mutation is found. Our findings confirm that KIT mutations, in contrast to previous white cohorts, are not common in both AM and NAM of the Chinese and do not necessarily correlate with c-kit expression. The significantly different association between the expression of c-kit immunoreactivities and the mortality risks of melanomas on acral versus nonacral sites might change site-specific targeted therapeutic concepts in melanoma in the future.

Dimerized Small-Molecular Acceptor Enables the Organic Bulk-Heterojunction Layer with High Thermal Stability.

Incorporation of a non-fullerene acceptor (NFA) into an organic bulk-heterojunction currently has realized the extendable spectral response and high photocurrent generation in organic photodiodes. However, to allow these organic materials to be industrially commercialized, the thermal stability which enables the materials to survive under the process integration and operation needs to be considered. Generally, NFA small molecules showed high crystallinity, which aggregated through heating and led to the poor thermal stability. To tackle the thermal stability issue of highly efficient NFAs, two IDIC-based NFA dimers─IDIC-T Dimer and IDIC-TT Dimer─were designed, synthesized, and characterized; the thermal stability of the BHJ layer incorporating these dimer molecules was evaluated and compared with that of the BHJ layer using the monomer, IDIC-4Cl, as acceptors. Eventually, a power conversion efficiency of 9.44% was achieved for organic photovoltaic devices based on the NFA dimer. The dimers also showed remarkable thermal stability than the IDIC-4Cl monomer, which provided a promising direction for the polymer/small-molecule system in organic photodiodes for industrial practicability.

Large-Area Nonfullerene Organic Photovoltaic Modules with a High Certified Power Conversion Efficiency.

Achieving large-area organic photovoltaic (OPV) modules with reasonable cost and performance is an important step toward commercialization. In this work, solution-processed conventional and inverted OPV modules with an area of 216 cm2 were fabricated by the blade coating method. Film uniformity was controlled by adjusting the fabrication parameters of the blade coating procedure. The influence of the concentration of the solutions of the interfacial materials on OPV module performance was investigated. For OPV modules based on the PM6:Y6 photoactive layer, a certificated power conversion efficiency (PCE) of 9.10% was achieved for the conventional OPV modules based on the TASiW-12 interfacial layer while a certificated PCE of 11.27% was achieved for the inverted OPV modules based on the polyethylenimine (PEI) interfacial layer. As for OPV modules based on a commercially available photoactive layer, PV-X Plus, a PCE of 8.52% was achieved in the inverted OPV modules. A halogen-free solvent, o-xylene, was used as the solvent for PV-X Plus, which makes the industrial production much more environmentally friendly.

Cancer-Associated Fibroblasts Promote Tumor Aggressiveness in Head and Neck Cancer through Chemokine Ligand 11 and C-C Motif Chemokine Receptor 3 Signaling Circuit.

The tumor microenvironment (TME) plays a crucial role in tumor progression. One of its key stromal components, cancer-associated fibroblasts (CAFs), may crosstalk with cancer cells by secreting certain cytokines or chemokines. However, which important mediator(s) are released by CAFs, and the underlying molecular mechanism, remain largely unknown. In the present study, we isolated patient-derived CAFs and normal fibroblasts (NFs). Using microarray analysis, we detected chemokine ligand 11 (CCL11) overexpression in CAFs compared to NFs. CCL11 administration promoted the migration and invasion of head and neck cancer (HNC) cells with enhanced cancer stem cell-like properties and induction of epithelial-to-mesenchymal transition. Furthermore, neutralization of CCL11 activity reversed the aggressive phenotype of CAF-induced cancer cells. Confocal microscopy showed colocalization of CCL11 and CC chemokine receptor 3 (CCR3) on HNC cells. Moreover, immunohistochemical analysis of clinical samples from 104 patients with HNC showed that expression of CCL11 and CCR3 were significantly correlated with poor overall survival (p = 0.003 and 0.044, respectively). Collectively, CCL11 expressed on CAFs promotes HNC invasiveness, and neutralization of CCL11 reverses this effect. We propose that the CCL11/CCR3 signaling circuit is a potential target for optimizing therapeutic strategies against HNC.

Loss of hepatic miR-194 promotes liver regeneration and protects from acetaminophen-induced acute liver injury.

The two microRNAs miR-192 and miR-194 are abundantly expressed in the liver and are considered serum biomarkers of liver injury. However, their role in the development of liver injury has not yet been determined. In this study, we generated miR-192/194 mutant mice and determined the effect of miR-192/194 loss on acetaminophen (APAP)-induced acute liver injury. With genetic depletion of miR-192/194, mutant mice were fertile and normally developed. No spontaneous liver injuries were observed in mutant mice. After APAP administration, mutant mice developed less severe liver damage than control mice. Specifically, mutant mice exhibited significantly lower serum alanine transaminase (ALT) levels and pericentral necrosis/apoptosis than control mice receiving APAP. ß-catenin signaling was activated during the early phase of liver injury. Activated ß-catenin signaling led to faster cellular proliferation and higher expression of AXIN2 and glutamine synthetases. After partial hepatectomy, the miR-192/194 mutant hepatocytes were more regenerative than control hepatocytes (as shown by BrdU incorporation). Moreover, in vitro experiments indicated that miR-194, but not miR-192, specifically repressed ß-catenin signaling, while animal experiments revealed that chemical-mediated knockdown of ß-catenin signaling compromised APAP resistance that liver protected from miR-192/194 genetic depletion. Collectively, our data indicated that the loss of miR-194 promoted liver regeneration and protected the liver from APAP-induced injury.

Bulk-Heterojunction Adjustment Enables a Self-filtering Organic Photodetector with a Narrowband Response.

Image-sensor technology is the foundation of many emerging applications, where the photodetector is designed to interact with incoming photons that have specific colors or wavelengths. A color filter is therefore crucial to enable the selective spectral response of the photodetector and to eliminate the crosstalk interference resulting from ambient lights. Unfortunately, a reduced detection sensitivity of the photodetector is inevitable due to an imperfect light filtering, which greatly limits the practical applications of selective-response photodetectors. Herein, we demonstrate a bulk-heterojunction (BHJ) organic composite featuring a self-filtering light responsive characteristic. Through a careful optimization of the BHJ film, the organic photodetector (OPD) demonstrates a high-selective spectral response to the infrared (IR) radiation without the need of applying a color filter. As a result, the self-filtering top-illuminated OPD exhibits a narrowband external quantum efficiency (EQE) of 53% with a narrow full width at half-maximum (fwhm) of 56 nm centering at 1080 nm. A high responsivity of 0.46 A W-1 is also achieved at 1080 nm wavelength due to the self-filtering characteristic.

Myoepithelial and oral intracranial myxoid mesenchymal tumor-like neoplasms as diagnostic considerations of the ever-expanding extracranial myxocollagenous tumors harboring FET-CREB fusions.

AIMS: Intracranial myxoid mesenchymal tumors (IMMTs) with fusions between EWSR1/FUS and CREB transcription factors have morphologic overlap with myxoid angiomatoid fibrous histiocytoma (mAFH) and myoepithelial tumor/carcinoma (MET/MEC). We aimed to study the clinicopathologic and genetic spectrum of extracranial IMMT-like tumors and their relationships with mAFH and MET/MEC. METHODS: Twelve extracranial tumors harboring EWSR1/FUS-CREB fusions across different histologic groups were characterized using RNA sequencing, FISH and/or RT-PCR. RESULTS: There were 4 IMMT-like neoplasms, 3 MET/MECs, and 5 mAFHs from the tibia (n=1), oral cavity (n=2), and soft tissues (n=9; 5 in the extremities), harboring EWSR1-ATF1 in 4 cases, FUS-CREM and EWSR1-CREM in 3 each, and EWSR1-CREB1 in 2. Multinodular growth, reticular/cording/trabecular arrangements, myxocollagenous matrix, and lymphocytic infiltrates variably prevailed among the 3 groups. mAFHs were characterized by cells with syncytial cytoplasm. IMMT-like neoplasms and MET/MECs shared cells with distinct boundaries, but only MET/MECs expressed GFAP and/or S100. MUC4 and ALK were expressed in some IMMT-like neoplasms (2/4; 2/4) and mAFH (2/5; 1/5). Pan-TRK reactivity was observed in two IMMT-like neoplasms with upregulated NTRK3 mRNA and one MEC. Local recurrences, typically ≥ 12 months postoperatively, developed in 2/3 IMMT-like neoplasms, 1/2 MET/MECs, and 0/4 mAFHs with follow-up. No definite associations were found between fusion types and histology, immunoprofile or outcome. CONCLUSIONS: We demonstrated the similarities and differences among 3 extracranial myxocollagenous tumor groups sharing EWSR1/FUS-CREB fusions. Oral IMMT-like neoplasms harboring FUS-CREM or EWSR1-ATF1 and FUS-CREM-positive.

Improved Blend Film Morphology and Free Carrier Generation Provide a High-Performance Ternary Polymer Solar Cell.

Non-fullerene organic photovoltaics (OPVs) have displayed the highest power conversion efficiencies (PCEs) among OPVs. Herein, we describe a two-donor (PM6, TPD-3F)/one-acceptor (Y6) ternary blend having an optimized blend morphology that leads to improved OPV performance. Because TPD-3F has a HOMO energy level deeper than that of PM6, the value of VOC of the corresponding ternary device increased. Good miscibility between PM6 and TPD-3F, in conjunction with device optimization through the use of 1-chloronaphthalene as an additive, provided an optimized ternary blend morphology for efficient exciton dissociation and carrier transport and, therefore, larger PCE. Compared with the preoptimized PM6:Y6 binary device, the ternary device functioned with improvements in its short-circuit current density, value of VOC, and fill factor. As a result, the device PCE improved from 15.5 ± 0.19 to 16.6 ± 0.25% under AM 1.5G (100 mW cm-2) irradiation. The champion cell exhibited a PCE of 17.0%-a value that is one of the highest for a ternary OPV. Furthermore, such devices exhibited outstanding shelf lifetimes, with long-term stability in air (25 °C, 40% humidity) without encapsulation; the performance remained high (at 15.4%) after storage for 820 h.

Interleukin-33-Enhanced CXCR4 Signaling Circuit Mediated by Carcinoma-Associated Fibroblasts Promotes Invasiveness of Head and Neck Cancer.

Despite recent advances, treatment for head and neck squamous cell carcinoma (HNSCC) has limited efficacy in preventing tumor progression. We confirmed previously that carcinoma-associated fibroblasts (CAF)-induced interleukin-33 (IL-33) contributed to cancer progression. However, the molecular mechanisms underlying the complex communication network of the tumor microenvironment merited further evaluation. To simulate the IL-33-induced autocrine signaling, stable clones of IL-33-overexpressing HNSCC cells were established. Besides well-established IL-33/ST2 and SDF1/CXCR4 (stromal-derived factor 1/C-X-C motif chemokine receptor 4) signaling, the CAF-induced IL-33 upregulated CXCR4 via cancer cell induction of IL-33 self-production. The IL-33-enhanced-CXCR4 regulatory circuit involves SDF1/CXCR4 signaling activation and modulates tumor behavior. An in vivo study confirmed the functional role of IL-33/CXCR4 in tumor initiation and metastasis. The CXCR4 and/or IL-33 blockade reduced HNSCC cell aggressiveness, with attenuated invasions and metastases. Immunohistochemistry confirmed that IL-33 and CXCR4 expression correlated significantly with disease-free survival and IL-33-CXCR4 co-expression predicted a poor outcome. Besides paracrine signaling, the CAF-induced IL-33 reciprocally enhanced the autocrine cancer-cell self-production of IL-33 and the corresponding CXCR4 upregulation, leading to the activation of SDF1/CXCR4 signaling subsequent to cancer progression. Thus, targeting the IL-33-enhanced-CXCR4 regulatory circuit attenuates tumor aggressiveness and provides a potential therapeutic option for improving the prognosis in HNSCC patients.

High-Performance Organic Solar Cells Featuring Double Bulk Heterojunction Structures with Vertical-Gradient Selenium Heterocyclic Nonfullerene Acceptor Concentrations.

In this study, we prepared organic photovoltaics (OPVs) featuring an active layer comprising double bulk heterojunction (BHJ) structures, featuring binary blends of a polymer donor and concentration gradients of two small-molecule acceptors. After forming the first BHJ structure by spin-coating, the second BHJ layer was transfer-printed onto the first using polydimethylsiloxane stamps. A specially designed selenium heterocyclic small-molecule acceptor (Y6-Se-4Cl) was employed as the second acceptor in the BHJ. X-ray photoelectron spectroscopy revealed that the two acceptors formed a gradient concentration profile across the active layer, thereby facilitating charge transportation. The best power conversion efficiencies (PCEs) for the double-BHJ-structured devices incorporating PM6:Y6-Se-4Cl/PM6:Y6 and PM6:Y6-Se-4Cl/PM6:IT-4Cl were 16.4 and 15.8%, respectively; these values were higher than those of devices having one-BHJ structures based on PM6:Y6-Se-4Cl (15.0%), PM6:Y6 (15.4%), and PM6:IT-4Cl (11.6%), presumably because of the favorable vertical concentration gradient of the selenium-containing small-molecule Y6-Se-4Cl in the active layer as well as some complementary light absorption. Thus, combining two BHJ structures with a concentration gradient of the two small-molecule acceptors can be an effective approach for enhancing the PCEs of OPVs.