RUNDC3A regulates SNAP25-mediated chemotherapy resistance by binding AKT in gastric neuroendocrine carcinoma (GNEC)

Gastric neuroendocrine carcinoma (GNEC) is a common type of neuroendocrine carcinoma (NEC) with a poor prognosis and limited therapeutic options. The underlying mechanisms of chemoresistance in patients with GNEC and those with NEC are largely unknown, and thus, reliable biomarkers and therapeutic targets that could improve treatment outcomes in patients with NECs are lacking. The aim of this study was to identify specific targets and investigate their roles in GNEC progression and treatment resistance. Differentially expressed genes (DEGs) were identified in GNEC specimens and were further analysed by focusing on their roles in chemoresistance. Gene Ontology (GO) and pathway enrichment analyses of GNEC DEGs revealed that synapse-related function was the most prominent cellular function perturbed in GNEC. SNAP25 was identified as the target gene involved in most of the enriched pathways. In vitro and in vivo experiments showed that SNAP25 plays a role in proliferation and chemoresistance in GNEC cell lines. AKT has been identified as a downstream target, and SNAP25 binds to AKT protein and promotes AKT protein half-life. Further analysis of other types of NEC as well as small cell lung cancer, which resembles NEC on a molecular level, has identified RUNDC3A as an upstream molecule that regulates SNAP25 expression and the associated phenotypes that could enhance chemoresistance in NECs. Our results show that SNAP25 expression in GNEC is mediated by RUNDC3A and promotes GNEC progression and chemoresistance via posttranslational modification of AKT. Thus, our results suggest that the RUNDC3A/SNAP25/Akt axis could be a potential therapeutic target in GNEC

Ultrathin Few-Layer GeP Nanosheets via Lithiation-Assisted Chemical Exfoliation and Their Application in Sodium Storage

2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Ultrathin few-layer materials have attracted intensive research attention because of their distinctive and unique properties. Few-layer GeP (FL-GP) is potentially interesting for application in electronics and optoelectronics because of its appropriate band gap and good stability under ambient conditions. Nevertheless, it is a challenge to achieve ultrathin few-layer or single layer GeP from exfoliation of bulk crystals. Here, a lithiation-assisted chemical exfoliation technique is employed to achieve FL-GP, in which the interlayer spacing can be efficiently enlarged after a preliminary lithium ion intercalation, allowing the bulk crystal to be readily exfoliated in a following ultrasonication. As a result, ultrathin FL-GP is obtained. In a demonstration, the FL-GP/reduced graphene oxide (rGO) demonstrates remarkable sodium storage performance. The FL-GP with a two-dimensional structure shortens the ion transport pathways and alleviates the volume variation during sodiation. Meanwhile, the rGO in the composite improves the conductivity of the whole electrode. The as-prepared FL-GP/rGO electrode exhibits a high capacity of 504.2 mAh g−1 at 100 mA g−1, remarkable rate performance, and superior cycling stability in the half cells. FL-GP/rGO//Na3V2(PO4)3 full cells are also assembled and demonstrated satisfactory electrochemical performance, indicating potential application of the as-prepared anode materials

Synthesis of renewable monomer 2, 5-bishydroxymethylfuran from highly concentrated 5-hydroxymethylfurfural in deep eutectic solvents

Abstract(#br)2, 5-Bishydroxymethylfuran (BHMF) has been currently emerged as a promising biomass-derived monomer. It is highly desirable to proceed a chemical process at a high substrate concentration, by which a facile and cost-effective separation of products can be expected. Herein, we report for the first time on the hydrogenation of highly concentrated 5-hydroxymethylfurfural (HMF) in deep eutectic solvents (DESs), giving a near quantitative selectivity towards BHMF in ChCl-glycerol DES at 25°C in 3h using NaBH 4 as the H-donor. DES is hailed as a new class of green solvent, in which HMF/BHMF could be stabilized by the strong hydrogen-bond interaction, and allowed the selective hydrogenation of HMF at high concentration up to 40wt%. Notably, the resulting BHMF could be facilely separated by extraction with ethyl acetate, and then high purity of BHMF with a desirable isolated yield around 80% was obtained after removing of ethyl acetate. Additionally, the reaction efficiency of HMF hydrogenation in DESs was verified to be strongly associated with the viscosity of DESs and the p K a value of hydrogen-bonding donor

Cascade conversion of furfural to fuel bioadditive ethyl levulinate over bifunctional zirconium-based catalysts

Abstract(#br)Biomass-derived ethyl levulinate (EL) is currently deemed as a promising fuel bioadditive to improve (bio)diesel combustion performance without the sacrifice of its octane number. In this contribution, a range of Zr–Al bimetallic catalysts were prepared for the cascade conversion of furfural to EL by the integration of transfer hydrogenation and ethanolysis in ethanol. The ratio of Lewis to Brønsted acid sites (L/B) could be tuned by the ratio of Al 2 O 3 to ZrO 2 over SBA-15 support. Among these catalysts, Zr–Al/SBA-15(30:10) with appropriate L/B ratio of 2.25 exhibited an outstanding catalytic performance to give a furfural (FF) conversion up to 92.8% with a EL selectivity as high as 71.4% at 453 K in 3 h

Case report:TP53 and RB1 loss may facilitate the transformation from lung adenocarcinoma to small cell lung cancer by expressing neuroendocrine markers

INTRODUCTION: Transformation from lung adenocarcinoma (LUAD) to small cell lung cancer (SCLC) is one of the mechanisms responsible for acquired EGFR-TKIs resistance. Although it rarely happens this event determines a rapid disease deterioration and needs specific treatment. PATIENT AND METHOD: We report a case of 75-year-old LUAD female with a p.L858R mutation in Epidermal Growth Factor Receptor (EGFR) who presented with SCLC transformation after responding to first line osimertinib treatment for only 6 months. To understand the underlying molecular mechanism, we retrospectively sequenced the first (LUAD) and the second (SCLC) biopsy using a 56 multi-gene panel. Immunohistochemistry (IHC) staining and Fluorescence In Situ Hybridization (FISH) was applied to confirm the genetic aberrations identified. RESULTS: EGFR p.E709A and p.L858R, Tumor Protein p53 (TP53) p.A159D and Retinoblastoma 1 (RB1) c.365-1G>A were detected in both the diagnostic LUAD and transformed SCLC samples. A high copy number gain for Proto-Oncogene C-Myc (MYC) and a Phosphoinositide 3-Kinase Alpha (PIK3CA) p.E545K mutation were found in the transformed sample specifically. Strong TP53 staining and negative RB1 staining were observed in both LUAD and SCLC samples, but FISH only identified MYC amplification in SCLC tissue. CONCLUSION: We consider the combined presence of MYC amplification with mutations in TP53 and RB1 as drivers of SCLC transformation. Our results highlight the need to systematically evaluate TP53 and RB1 status in LUAD patients to offer a different therapeutic strategy

A flexible Cu-based catalyst system for the transformation of fructose to furanyl ethers as potential bio-fuels

Abstract(#br)Biomass-derived furanyl ethers, such as 5-alkoxymethylfurfurals (AMFs) and 2,5-bis(alkoxymethyl)furans (BAMFs), can be employed as promising biofuels or additives. The development of multifunctional catalysts for the efficient production of furanyl ethers from sugars through 5-hydroxymethylfurfural (HMF) as an intermediate is highly desirable but challenging, because multiple reactions including dehydration, etherification and hydrogenation get involved and the side reaction of sugars and HMF to form humins is inevitable. In this contribution, we found that the introduction of CuO resulted in the generation of Lewis acid sites at the cost of Bronsted acid sites over CuO-USY catalysts through the formation of Al-O-Cu(II) species. The dispersity of CuO particles and the amount of Lewis acid sites could be manipulated by adjusting the loading of CuO. If 5 wt% CuO was supported on USY zeolite to give a CuO(5)-USY catalyst, CuO particles with a high dispersity (36.4%) afforded abundant Lewis acid sites (457.1 μ mol/g). Lewis acid over CuO(5)-USY greatly promoted the acid-catalyzed dehydration of fructose to HMF and HMF etherification to AMFs, resulting in a HMF yield up to 86.2% from fructose and AMFs yields greater than 90% from HMF. Interestingly, a combination of CuO(5)-USY and a small amount of metallic Cu powder was able to offer desirable BAMFs yields by the reductive etherification of HMF under hydrogen atmosphere. As a result, 5-methoxymethylfurfural (MMF) of 79.6% and 2,5-bis(methoxymethyl)furan (BMMF) yield of 74.5% were achieved from fructose through HMF as an intermediate in the presence of CuO(5)-USY alone or with metallic Cu as a co-catalyst. Therefore, the above Cu-based catalyst system holds the promise to flexibly produce a family of AMFs or BAMFs from fructose via a facile two-step approach

Case report: TP53 and RB1 loss may facilitate the transformation from lung adenocarcinoma to small cell lung cancer by expressing neuroendocrine markers

IntroductionTransformation from lung adenocarcinoma (LUAD) to small cell lung cancer (SCLC) is one of the mechanisms responsible for acquired EGFR-TKIs resistance. Although it rarely happens this event determines a rapid disease deterioration and needs specific treatment.Patient and methodWe report a case of 75-year-old LUAD female with a p.L858R mutation in Epidermal Growth Factor Receptor (EGFR) who presented with SCLC transformation after responding to first line osimertinib treatment for only 6 months. To understand the underlying molecular mechanism, we retrospectively sequenced the first (LUAD) and the second (SCLC) biopsy using a 56 multi-gene panel. Immunohistochemistry (IHC) staining and Fluorescence In Situ Hybridization (FISH) was applied to confirm the genetic aberrations identified.ResultsEGFR p.E709A and p.L858R, Tumor Protein p53 (TP53) p.A159D and Retinoblastoma 1 (RB1) c.365-1G>A were detected in both the diagnostic LUAD and transformed SCLC samples. A high copy number gain for Proto-Oncogene C-Myc (MYC) and a Phosphoinositide 3-Kinase Alpha (PIK3CA) p.E545K mutation were found in the transformed sample specifically. Strong TP53 staining and negative RB1 staining were observed in both LUAD and SCLC samples, but FISH only identified MYC amplification in SCLC tissue.ConclusionWe consider the combined presence of MYC amplification with mutations in TP53 and RB1 as drivers of SCLC transformation. Our results highlight the need to systematically evaluate TP53 and RB1 status in LUAD patients to offer a different therapeutic strategy

Automatic Recognition of Laryngoscopic Images Using a Deep-Learning Technique

Objectives/Hypothesis: To develop a deep-learning–based computer-aided diagnosis system for distinguishing laryngeal neoplasms (benign, precancerous lesions, and cancer) and improve the clinician-based accuracy of diagnostic assessments of laryngoscopy findings. Study Design: Retrospective study. Methods: A total of 24,667 laryngoscopy images (normal, vocal nodule, polyps, leukoplakia and malignancy) were collected to develop and test a convolutional neural network (CNN)-based classifier. A comparison between the proposed CNN-based classifier and the clinical visual assessments (CVAs) by 12 otolaryngologists was conducted. Results: In the independent testing dataset, an overall accuracy of 96.24% was achieved; for leukoplakia, benign, malignancy, normal, and vocal nodule, the sensitivity and specificity were 92.8% vs. 98.9%, 97% vs. 99.7%, 89% vs. 99.3%, 99.0% vs. 99.4%, and 97.2% vs. 99.1%, respectively. Furthermore, when compared with CVAs on the randomly selected test dataset, the CNN-based classifier outperformed physicians for most laryngeal conditions, with striking improvements in the ability to distinguish nodules (98% vs. 45%, P <.001), polyps (91% vs. 86%, P <.001), leukoplakia (91% vs. 65%, P <.001), and malignancy (90% vs. 54%, P <.001). Conclusions: The CNN-based classifier can provide a valuable reference for the diagnosis of laryngeal neoplasms during laryngoscopy, especially for distinguishing benign, precancerous, and cancer lesions. Level of Evidence: NA Laryngoscope, 130:E686–E693, 2020