Abstract The utilization of alloyed 2D transition metal dichalcogenides (TMDs) has become a pivotal approach for addressing challenges in material applications. The judicious selection of dopant ...constituents offers a potent means to finely modulate the materials' bandgap, consequently broadening the potential applications of 2D materials. In the context of an investigation, Mo1−x−yRexWyS2 is successfully synthesized using chemical vapor deposition. With a bandgap of 1.33 eV, this material exhibits promising prospects for application in the realm of optoelectronics. This advancement enables the fabrication of the Mo1−x−yRexWyS2 photodetector. The rigorous testing and analysis of photoelectric performance reveal significant improvements in both responsivity and response speed compared to analogous detectors. This accomplishment not only furnishes a novel paradigm for the advancement of photodetectors but also contributes fresh insights to the domain of alloyed 2D TMDs.
NUT carcinoma (NC) is an extremely aggressive tumor and current treatment regimens offer patients a median survival of six months only. This article reports on the first in vitro studies using ...immunovirotherapy as a promising therapy option for NC and its feasible combination with BET inhibitors (iBET). Using NC cell lines harboring the BRD4-NUT fusion protein, the cytotoxicity of oncolytic virus
(T-VEC) and the iBET compounds BI894999 and GSK525762 were assessed in vitro in monotherapeutic and combinatorial approaches. Viral replication, marker gene expression, cell proliferation, and IFN-β dependence of T-VEC efficiency were monitored. T-VEC efficiently infected and replicated in NC cell lines and showed strong cytotoxic effects. This implication could be enhanced by iBET treatment following viral infection. Viral replication was not impaired by iBET treatment. In addition, it was shown that pretreatment of NC cells with IFN-β does impede the replication as well as the cytotoxicity of T-VEC. T-VEC was found to show great potential for patients suffering from NC. Of note, when applied in combination with iBETs, a reinforcing influence was observed, leading to an even stronger anti-tumor effect. These findings suggest combining virotherapy with diverse molecular therapeutics for the treatment of NC.
We present the first known case of a patient with BRD2::NUTM1-driven NUT carcinoma. A 59-year-old woman presented with poorly differentiated squamous cell lung cancer metastatic to the pleura. ...Eventually, a positive NUT immunohistochemistry, NUT fluorescence in situ hybridization, and RNA next-generation sequencing with a BRD2::NUTM1 fusion led to the diagnosis of NUT carcinoma. She received multiple lines of chemotherapy with response and is still alive at 2 years postdiagnosis. This report expands on the known fusions in NUT carcinoma and highlights potential differences in patient prognosis on the basis of gene fusion partners.
Stacking of van der Waals (vdW) heterostructures and chemical element doping have emerged as crucial methods for enhancing the performance of semiconductors. This study proposes a novel strategy for ...modifying heterostructures by codoping MoS2 with two elements, Re and W, resulting in the construction of a RexWyMo1-x-yS2/WSe2 heterostructure for the preparation of photodetectors. This approach incorporates multiple strategies to enhance the performance, including hybrid stacking of materials, type-II band alignment, and regulation of element doping. As a result, the RexWyMo1-x-yS2/WSe2 devices demonstrate exceptional performance, including high photoresponsivity (1550.22 A/W), high detectivity (8.17 × 1013 Jones), and fast response speed (rise/fall time, 190 ms/1.42 s). Moreover, the ability to tune the band gap through element doping enables spectral response in the ultraviolet (UV), visible light, and near-infrared (NIR) regions. This heterostructure fabrication scheme highlights the high sensitivity and potential applications of vdW heterostructure (vdWH) in optoelectronic devices.Stacking of van der Waals (vdW) heterostructures and chemical element doping have emerged as crucial methods for enhancing the performance of semiconductors. This study proposes a novel strategy for modifying heterostructures by codoping MoS2 with two elements, Re and W, resulting in the construction of a RexWyMo1-x-yS2/WSe2 heterostructure for the preparation of photodetectors. This approach incorporates multiple strategies to enhance the performance, including hybrid stacking of materials, type-II band alignment, and regulation of element doping. As a result, the RexWyMo1-x-yS2/WSe2 devices demonstrate exceptional performance, including high photoresponsivity (1550.22 A/W), high detectivity (8.17 × 1013 Jones), and fast response speed (rise/fall time, 190 ms/1.42 s). Moreover, the ability to tune the band gap through element doping enables spectral response in the ultraviolet (UV), visible light, and near-infrared (NIR) regions. This heterostructure fabrication scheme highlights the high sensitivity and potential applications of vdW heterostructure (vdWH) in optoelectronic devices.
van der Waals (vdW) heterogeneous integration and doping engineering have emerged as crucial factors in advancing the development of functional device systems. This work presents a fully vertical ...2D/3D vdW stacking p‐MoxRe1‐xS2/GaN (x = 0.10 ± 0.02) heterojunction photodetector, integrating multiple strategies for enhanced performance, such as mixed‐dimensional stacking, p‐type doping, vertical device design, and type‐II band alignment. By integrating horizontal, vertical, and quasi‐vertical devices on a Free‐standing (FS)‐GaN substrate, the vertical p‐MoxRe1‐xS2/GaN device demonstrates superior performance, including high Ilight/Idark ratio (1.48 × 106), large Responsivity (888.69 AW−1), high specific detectivity (D*) (6.13 × 1014 Jones), and fast response speed (rise/decay time of 181 ms/259 ms). Moreover, the spectral response encompasses the ultraviolet (UV), visible, and near‐infrared (NIR) regions through energy band integration and bandgap modulation. This design surpasses previous devices, highlighting the potential of highly sensitive and micro‐integrated optoelectronic devices enabled by vertical vdW heterogeneous integration.
Large‐area p‐MoxRe1‐xS2 films are grown on Free‐standing GaN substrates using one‐step CVD. A fully vertical vdW heterostructure photodetector exhibits improved performance with a high photo Ion/Ioff ratio (1.48 × 106), specific detectivity (D*) (7.13 × 1014 Jones), and fast response time (181 ms/259 ms). Enhancements are attributed to the built‐in electric field and type‐II band alignment at the p‐MoxRe1‐xS2/GaN interface. The vertical structure avoids etching damage and utilizes internal carriers in bulk GaN, enhancing electronic and optoelectronic device performance.
NUT carcinoma (NC) is an aggressive squamous carcinoma defined by the BRD4-NUT fusion oncoprotein. Routinely effective systemic treatments are unavailable for most NC patients. The lack of an ...adequate animal model precludes identifying and leveraging cell-extrinsic factors therapeutically in NC. Here, we created a genetically engineered mouse model (GEMM) of NC that forms a Brd4::NUTM1 fusion gene upon tamoxifen induction of Sox2-driven Cre. The model displayed complete disease penetrance, with tumors arising from the squamous epithelium weeks after induction and all mice succumbing to the disease shortly thereafter. Closely resembling human NC (hNC), GEMM tumors (mNC) were poorly differentiated squamous carcinomas with high expression of MYC that metastasized to solid organs and regional lymph nodes. Two GEMM-derived cell lines were developed whose transcriptomic and epigenetic landscapes harbored key features of primary GEMM tumors. Importantly, GEMM tumor and cell line transcriptomes co-classified with those of human NC. BRD4-NUT also blocked differentiation and maintained the growth of mNC as in hNC. Mechanistically, GEMM primary tumors and cell lines formed large histone H3K27ac-enriched domains, termed megadomains, that were invariably associated with the expression of key NC-defining proto-oncogenes, Myc and Trp63. Small-molecule BET bromodomain inhibition (BETi) of mNC induced differentiation and growth arrest and prolonged survival of NC GEMMs, as it does in hNC models. Overall, tumor formation in the NC GEMM is definitive evidence that BRD4-NUT alone can potently drive the malignant transformation of squamous progenitor cells into NC.
The development of an immunocompetent model of NUT carcinoma that closely mimics the human disease provides a valuable global resource for mechanistic and preclinical studies to improve treatment of this incurable disease.
Abstract van der Waals (vdW) heterogeneous integration and doping engineering have emerged as crucial factors in advancing the development of functional device systems. This work presents a fully ...vertical 2D/3D vdW stacking p‐Mo x Re 1‐ x S 2 /GaN ( x = 0.10 ± 0.02) heterojunction photodetector, integrating multiple strategies for enhanced performance, such as mixed‐dimensional stacking, p ‐type doping, vertical device design, and type‐II band alignment. By integrating horizontal, vertical, and quasi‐vertical devices on a Free‐standing (FS)‐GaN substrate, the vertical p‐Mo x Re 1‐ x S 2 /GaN device demonstrates superior performance, including high I light / I dark ratio (1.48 × 10 6 ), large Responsivity (888.69 AW −1 ), high specific detectivity ( D * ) (6.13 × 10 14 Jones), and fast response speed (rise/decay time of 181 ms/259 ms). Moreover, the spectral response encompasses the ultraviolet (UV), visible, and near‐infrared (NIR) regions through energy band integration and bandgap modulation. This design surpasses previous devices, highlighting the potential of highly sensitive and micro‐integrated optoelectronic devices enabled by vertical vdW heterogeneous integration.
Vanadium-chromium oxides (VCrO) were usually prepared by high-temperature solid-state reactions; however, mixed phases were frequently produced and the morphology of the products was not well ...controlled. In this work, we prepared amorphous VCrO precursors by using V2O5 and CrO3 and alcohols or mixtures of alcohol and water via solvothermal reaction at 180 °C. The precursors were then calcined under nitrogen at various temperatures. The products were characterized by powder X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy. It was revealed that pure-phase nanocrystalline orthorhombic CrVO4 was obtained when methanol or methanol/water was used as the solvothermal medium and the precursor was calcined at 700 °C. The size of the CrVO4 crystals was around 500 nm when methanol was used, whereas it reduced significantly to less than 50 nm when a mixture of methanol and water was used. The sizes could be effectively tuned from 10 to 50 nm by varying the methanol/water volume ratio. To the best of our knowledge, this is the first report on the synthesis of pure-phase CrVO4 nanocrystals. The nano-CrVO4 showed almost the highest catalytic activity for the ammoxidation of 2,6-dichlorotoluene to 2,6-dichlorobenzonitrile among the reported bi-component composite oxides, owing to its smaller particle size, larger specific surface area, and more exposed active centers.
Nano-CrVO4 was obtained for the first time through solvothermal reaction of V2O5 and CrO3 in either methanol or methanol/water mixtures at 180 °C to prepare the precursor followed by calcination at 700 °C, which showed almost the highest catalytic activity among the bi-component composite oxides reported for the ammoxidation of 2,6-dichlorotoluene to 2,6-dichlorobenzonitrile.
NUT carcinoma (NC), characterized most commonly by the BRD4-NUTM1 fusion, is a rare, aggressive variant of squamous carcinoma with no effective treatment. BRD4-NUT drives growth and maintains the ...poorly differentiated state of NC by activating pro-growth genes such as
, through the formation of massive, hyperacetylated, superenhancer-like domains termed megadomains. BRD4-NUT-mediated hyperacetylation of chromatin is facilitated by the chromatin-targeting tandem bromodomains of BRD4, combined with NUT, which recruits the histone acetyltransferase, p300. Here, we developed a high-throughput small-molecule screen to identify inhibitors of transcriptional activation by NUT. In this dCAS9-based GFP-reporter assay, the strongest hits were diverse histone deacetylase (HDAC) inhibitors. Two structurally unrelated HDAC inhibitors, panobinostat and the novel compound, IRBM6, both repressed growth and induced differentiation of NC cells in proportion to their inhibition of NUT transcriptional activity. These two compounds repressed transcription of megadomain-associated oncogenic genes, such as
and
, while upregulating pro-differentiation, non-megadomain-associated genes, including
,
, and key cell-cycle regulators, such as
. The transcriptional changes correlate with depletion of BRD4-NUT from megadomains, and redistribution of the p300/CBP-associated chromatin acetylation mark, H3K27ac, away from megadomains toward regular enhancer regions previously populated by H3K27ac. In NC xenograft models, we demonstrated that suppression of tumor growth by panobinostat was comparable with that of bromodomain inhibition, and when combined they improved both survival and growth suppression. IMPLICATIONS: The findings provide mechanistic and preclinical rationale for the use of HDAC inhibitors, alone or combined with other agents, in the treatment of NUT carcinoma.
PDF
