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The current criteria for utilizing MDM2 Fluorescence In Situ Hybridization (FISH) in adipose-derived tumors were first introduced in 2015 and have been widely adopted. However, these criteria may fail to identify some atypical lipomatous tumors / well-differentiated liposarcoma (ALT/WDL) with mature adipocytic morphology in clinical practice, possibly due to the fact that the existing criteria are primarily based on biopsy cases. Hence, a criterion based on resection cases is needed. In this study, we included 87 adipose tissue tumors with mature adipocytic morphology which were first resected, as well as 9 consultation cases and 25 recurrent resection cases. The final diagnosis was based on MDM2 amplification status. Among the 87 first-time resection cohort, MDM2 FISH amplification was observed in only 2 (5%) of the 39 superficial cases. Marginal infiltration was significantly different in both the MDM2 FISH negative and positive groups (p < 0.05). Of the 37 intramuscular tumors, 17 (46%) showed MDM2 FISH amplification. The MDM2 amplification positive group had a larger tumor size than MDM2 amplification negative group (p = 0.042). Tumors of larger size (≥11 cm) were highly correlated with MDM2 amplification (p = 0.003), but still, 35.3% of the MDM2 amplification-positive cases had tumor sizes less than 11 cm. Eight (66.7%) out of twelve retroperitoneal/ pelvic cases were MDM2 FISH positive. Among the 25 recurrent cases, twenty (80%) of them had MDM2 FISH amplification. In conclusion, we recommend MDM2 FISH for: 1. superficial cases with marginal infiltration based on adequate margin sampling; 2. all intramuscular tumors, retroperitoneal/pelvic tumors and recurrent tumors, both in resection cases and biopsy cases.
Subject(s)
Lipoma , Liposarcoma , Retroperitoneal Neoplasms , Humans , Liposarcoma/diagnosis , Liposarcoma/genetics , Liposarcoma/pathology , In Situ Hybridization, Fluorescence , Gene Amplification , Proto-Oncogene Proteins c-mdm2/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , Neoplasm Recurrence, Local/diagnosis , Lipoma/diagnosis , Biomarkers, TumorABSTRACT
Solitary fibrous tumors (SFTs) are rare mesenchymal tumors with unpredictable evolution and with a recurrence or metastasis rate of 10-40%. Current medical treatments for relapsed SFTs remain ineffective. Here, we identify potential therapeutic targets and risk factors, including IDH1 p.R132S, high PD-L1 expression, and predominant macrophage infiltration, suggesting the potential benefits of combinational immune therapy and targeted therapy for SFTs. An integrated risk model incorporating mitotic count, density of Ki-67+ cells and CD163+ cells, MTOR mutation is developed, applying a discovery cohort of 101 primary non-CNS patients with negative tumor margins (NTM) and validated in three independent cohorts of 210 SFTs with the same criteria, and in 36 primary CNS SFTs with NTM. Compared with the existing models, our model shows significantly improved efficacy in identifying high-risk primary non-CNS and CNS SFTs with NTM for tumor progression.Our findings hold promise for advancing therapeutic strategies and refining risk prediction in SFTs.
Subject(s)
Severe Fever with Thrombocytopenia Syndrome , Soft Tissue Neoplasms , Solitary Fibrous Tumors , Humans , Solitary Fibrous Tumors/genetics , Solitary Fibrous Tumors/therapy , Solitary Fibrous Tumors/metabolism , Risk Factors , Soft Tissue Neoplasms/pathology , Risk AssessmentABSTRACT
Objective To explore the clinicopathological features and prognosis of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification.Methods The pathological sections were reviewed.EGFR mutation was detected by amplification refractory mutation system-quantitative real-time polymerase chain reaction,and C-MET amplification by fluorescence in situ hybridization.The clinicopathological features and survival data of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification were analyzed retrospectively.Results In 11 cases of EGFR mutation combined with C-MET amplification,complex glands and solid high-grade components were observed under a microscope in 10 cases except for one case with a cell block,the tissue structure of which was difficult to be evaluated.The incidence of lung adenocarcinoma in the patients with EGFR mutation combined with C-MET amplification at clinical stage â £ was higher than that in the EGFR mutation or C-MET amplification group (all P<0.001),whereas the difference was not statistically significant between the EGFR mutation group and C-MET amplification group at each clinical stage (all P>0.05).There was no significant difference in the trend of survival rate between EGFR gene group and C-MET amplification group (χ2=0.042,P=0.838),while the survival of the patients with EGFR mutation combined with C-MET amplification was worse than that of the patients with EGFR mutation (χ2=246.72,P<0.001) or C-MET amplification (χ2=236.41,P<0.001).Conclusions The patients newly diagnosed with lung adenocarcinoma with EGFR mutation plus C-MET amplification demonstrate poor histological differentiation,rapid progress,and poor prognosis.The patients are often in the advanced stage when being diagnosed with cancer.Attention should be paid to this concurrent adverse driving molecular event in clinical work.With increasing availability,the inhibitors targeting C-MET may serve as an option to benefit these patients in the near future.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , In Situ Hybridization, Fluorescence , Retrospective Studies , Prognosis , Adenocarcinoma of Lung/genetics , Mutation , Lung Neoplasms/genetics , ErbB Receptors/geneticsABSTRACT
Hydrazine-assisted water electrolysis offers a feasible path for low-voltage green hydrogen production. Herein, the design and synthesis of ultrathin RhRu0.5 -alloy wavy nanowires as bifunctional electrocatalysts for both the anodic hydrazine oxidation reaction (HzOR) and the cathodic hydrogen evolution reaction (HER) is reported. It is shown that the RhRu0.5 -alloy wavy nanowires can achieve complete electrooxidation of hydrazine with a low overpotential and high mass activity, as well as improved performance for the HER. The resulting RhRu0.5 bifunctional electrocatalysts enable, high performance hydrazine-assisted water electrolysis delivering a current density of 100 mA cm-2 at an ultralow cell voltage of 54 mV and a high current density of 853 mA cm-2 at a cell voltage of 0.6 V. The RhRu0.5 electrocatalysts further demonstrate a stable operation at a high current density of 100 mA cm-2 for 80 hours of testing period with little irreversible degradation. The overall performance greatly exceeds that of the previously reported hydrazine-assisted water electrolyzers, offering a pathway for efficiently converting hazardous hydrazine into molecular hydrogen.
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OBJECTIVES: To construct effective prediction models for neoadjuvant radiotherapy (RT) and targeted therapy based on whole-tumor texture analysis of multisequence MRI for soft tissue sarcoma (STS) patients. METHODS: Thirty patients with STS of the extremities or trunk from a prospective phase II trial were enrolled for this analysis. All patients underwent pre- and post-neoadjuvant RT MRI examinations from which whole-tumor texture features were extracted, including T1-weighted with fat saturation and contrast enhancement (T1FSGd), T2-weighted with fat saturation (T2FS), and diffusion-weighted imaging (DWI) sequences and their corresponding apparent diffusion coefficient (ADC) maps. According to the postoperative pathological results, the patients were divided into pathological complete response (pCR) and non-pCR (N-pCR) groups. pCR was defined as less than 5% of residual tumor cells by postoperative pathology. Delta features were defined as the percentage change in a texture feature from pre- to post-neoadjuvant RT MRI. After data reduction and feature selection, logistic regression was used to build prediction models. ROC analysis was performed to assess the diagnostic performance. RESULTS: Five of 30 patients (16.7%) achieved pCR. The Delta_Model (AUC 0.92) had a better predictive ability than the Pre_Model (AUC 0.78) and Post_Model (AUC 0.76) and was better than AJCC staging (AUC 0.52) and RECIST 1.1 criteria (AUC 0.52). The Combined_Model (pre, post, and delta features) had the best predictive performance (AUC 0.95). CONCLUSION: Whole-tumor texture analysis of multisequence MRI can well predict pCR status after neoadjuvant RT and targeted therapy in STS patients, with better performance than RECIST 1.1 and AJCC staging. KEY POINTS: ⢠MRI multisequence texture analysis could predict the efficacy of neoadjuvant RT and targeted therapy for STS patients. ⢠Texture features showed incremental value beyond routine clinical factors. ⢠The Combined_Model with features at multiple time points showed the best performance.
Subject(s)
Rectal Neoplasms , Sarcoma , Soft Tissue Neoplasms , Humans , Diffusion Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/methods , Neoadjuvant Therapy/methods , Prospective Studies , Rectal Neoplasms/pathology , Retrospective Studies , Sarcoma/diagnostic imaging , Sarcoma/therapy , Treatment OutcomeABSTRACT
Objective To analyze the clinicopathological characteristics of lymphadenitis caused by Talaromyces marneffei (TM).Method s The clinical data,pathological features,pathogen examination,and treatment of 15 cases of TM-caused lymphadenitis were analyzed retrospectively.Results The 15 cases included 14 males and 1 females,who were aged 26-67 years,with an average age of (49.1±11.87) years.The 15 cases,including 13 cases of acquired immunodeficiency syndrome and 2 cases of diabetes mellitus,were accompanied by superficial lymph node enlargement in the neck and supraclavicular,axillary,and inguinal regions.The structure of cord-like lymph node tissue punctured by thick needle was completely or partially replaced by inflammatory lesions. Under microscope,8 cases showed mainly diffuse infiltration of phagocytes with pathogens;5 cases presented mainly extensive coagulation necrosis with a small amount of pathogens and nuclear debris;2 cases were characterized by small nodular hyperplasia of fibroblasts,formation of granulomatous structure,and scattered distribution of a few multinucleated giant cells.The pathogens were relatively consistent in size and shape,which were round,oval or sausage-shaped and clustered like mulberry.Diastase periodic acid-Schiff staining and hexamine silver staining highlighted the bacterial structure with transverse septum.TM growth was detected in the blood,alveolar lavage fluid,sputum or lymph node extract fungal culture of the 15 patients.Owing to the adequate antifungal treatment in time,these 15 patients were discharged after their conditions were improved.Conclusion Lymphadenitis is one of the major manifestations of the systemic invasion of TM at the late stage,which is tended to be misdiagnosed.Through core needle biopsy of lymph node,it can be diagnosed as soon as possible to avoid delayed treatment and improve the cure rate.
Subject(s)
Lymphadenitis , Mycoses , Talaromyces , Adult , Aged , Biopsy, Large-Core Needle , Female , Humans , Lymphadenitis/diagnosis , Lymphadenitis/microbiology , Male , Middle Aged , Mycoses/complications , Retrospective StudiesABSTRACT
Mineral nutrition of orchard soil is critical for the growth of fruit trees and improvement of fruit quality. In the present study, the effects of soil mineral nutrients on peach fruit quality were studied by using artificial neural network model. The results showed that the four established ANN models had the highest prediction accuracy (R 2 = .9735, .9607, .9036, and .9440, respectively). The results of prediction model sensitivity analysis showed that available B, Ca, N, and K in the soil had the greatest influence on the single fruit weight, available Fe, K, B, and Ca in the soil had the greatest effect on fruit soluble solid content, available Ca, N, B, and K in the soil had the greatest influence on the fruit titratable acid content, and available Ca, Fe, N, and Mn in the soil had the greatest effect on fruit edible rate. The response surface methodology analysis determined the optimal range of these mineral elements, which is critical for guiding precision fertilization in peach orchards and improving peach fruit quality.
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Enhancing the terrestrial ecosystem carbon sink (referred to as terrestrial C sink) is an important way to slow down the continuous increase in atmospheric carbon dioxide (CO2) concentration and to achieve carbon neutrality target. To better understand the characteristics of terrestrial C sinks and their contribution to carbon neutrality, this review summarizes major progress in terrestrial C budget researches during the past decades, clarifies spatial patterns and drivers of terrestrial C sources and sinks in China and around the world, and examines the role of terrestrial C sinks in achieving carbon neutrality target. According to recent studies, the global terrestrial C sink has been increasing from a source of (-0.2±0.9) Pg C yr-1 (1 Pg=1015 g) in the 1960s to a sink of (1.9±1.1) Pg C yr-1 in the 2010s. By synthesizing the published data, we estimate terrestrial C sink of 0.20-0.25 Pg C yr-1 in China during the past decades, and predict it to be 0.15-0.52 Pg C yr-1 by 2060. The terrestrial C sinks are mainly located in the mid- and high latitudes of the Northern Hemisphere, while tropical regions act as a weak C sink or source. The C balance differs much among ecosystem types: forest is the major C sink; shrubland, wetland and farmland soil act as C sinks; and whether the grassland functions as C sink or source remains unclear. Desert might be a C sink, but the magnitude and the associated mechanisms are still controversial. Elevated atmospheric CO2 concentration, nitrogen deposition, climate change, and land cover change are the main drivers of terrestrial C sinks, while other factors such as fires and aerosols would also affect ecosystem C balance. The driving factors of terrestrial C sink differ among regions. Elevated CO2 concentration and climate change are major drivers of the C sinks in North America and Europe, while afforestation and ecological restoration are additionally important forcing factors of terrestrial C sinks in China. For future studies, we recommend the necessity for intensive and long term ecosystem C monitoring over broad geographic scale to improve terrestrial biosphere models for accurately evaluating terrestrial C budget and its dynamics under various climate change and policy scenarios.
Subject(s)
Carbon Sequestration , Ecosystem , Carbon Cycle , Carbon Dioxide , China , Climate ChangeABSTRACT
Background. Synovial sarcoma (SS) is a rare soft tissue sarcoma. Available data regarding survival outcomes of patients with SS still remains limited. In this study, a single center retrospective analysis was performed to investigate the clinical characteristics, pathology and survival outcomes in patients with SS in China. Methods. Patient data were systematically reviewed at the National Cancer Center from January 2015 to December 2020. The general information and treatment condition of patients were collected. Overall survival (OS) was evaluated using the Kaplan-Meier and Cox regression method. Results. A total of 237 consecutive patients were included in this study (follow-up cut-off date: December, 2020). The median age of patients involved was 35 years (ranging from 5 to 83 years) and the mean tumor diameter was 5.3â cm (ranging from .2 to 26.0â cm). The main findings of the immunohistochemical staining analyses were EMA (111/156) (71%), keratin 7 (32/64) (50.0%), keratin 8/18 (12/20) (60%), keratin 19 (42/70) (60%), S-100 (18/160) (11%), BCL2 (128/134) (96%), CD99 (137/148) (93%) and TLE1 (23/26) (88%). It was found that 109 patients (66%) were presented with monophasic subtype and 55 (34%) with biphasic subtype. A total of 137 patients were tested by FISH method and 119 patients (87%) demonstrated SS18 rearrangement, whereas 18 patients (13%) did not show SS18 rearrangement. Generally, it was found that the 3-year OS rate was 86% and the 3-year DFS was 55%. Results of univariate analysis revealed that age, tumor size, tumor site, radiotherapy and targeted therapy were significantly correlated with the overall survival (P < .05). Further, multivariate Cox regression analysis revealed that age, tumor size and radiotherapy were significantly associated with OS (P < .05). Conclusions. In conclusion, this study shows that the outcomes of patients with SS significantly decrease with age and tumor size. It was evident that radiotherapy is an independent and positive prognostic factor for patients with SS. In addition, it was shown that the prognosis of SS varies with tumor location. For instance, primary tumors in lower extremities have a higher prognosis, whereas tumors located in thorax have a lower prognosis.
Subject(s)
Sarcoma, Synovial , Soft Tissue Neoplasms , Humans , In Situ Hybridization, Fluorescence , Prognosis , Retrospective Studies , Sarcoma, Synovial/diagnosis , Sarcoma, Synovial/therapyABSTRACT
Rare earth (RE) based halide solid electrolytes (HEs) are recently considered as research hotspots in the field of all-solid-state batteries (ASSBs). The RE-based HEs possess high ionic conductivity, credible deformability, and good stability, which can bring excellent electrochemical performances for ASSBs. However, the conventional synthetic methods of RE HEs are a mechanochemical process and co-melting strategy, both approaches require expensive raw materials and sophisticated equipment. Therefore, a lot of research work is required to promote the preparation methods for these promising SSEs in ASSBs. Thus, a vacuum evaporation-assisted synthesis method is developed for the massive synthesis of HEs. The as-prepared Li3 HoBr6 (LHB) has a high lithium-ion conductivity close to the mS cm-1 level and the LHB-based Li-Se ASSBs can be assembled by cold pressing. Theoretical calculations have revealed that the Li migrations are highly preferred in Li3 HoBr6 owing to the low energy cost and high tolerance of stable structure. The tetrahedral and octahedral pathways are responsible for Li migrations in short and long ranges, respectively. The results show that the LHB-based Li-Se battery has good stability and rate performance, indicating that LHB has potential application in the field of ASSBs.
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Rare-earth (RE) solid-state halide electrolytes have been extensively studied recently in the field of lithium (Li) ion all-solid-state batteries (ASSBs) due to their excellent electrochemical performances. Herein, a new RE-based solid halide electrolyte Li3HoBr6 (LHB) has been synthesized and exhibits high Li ion conductivity up to mS cm-1 at room temperature. Theoretical calculations have identified four different Li ion migration pathways, in which the out-of-plane pathways are much more favorable than the direct in-plane pathways. In addition, LHB has a wider electrochemical window in comparison to a sulfide solid electrolyte and good deformability. The LHB-based Li-sulfur ASSB assembled by cold pressing can exhibit good cycling stability with high Coulombic efficiency, which shows that LHB has potential application in ASSBs.
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Rare-earth-containing perovskite (RECP) materials have been extensively studied in various fields for their outstanding optical, electrical, magnetic and catalytic properties. In order to understand the clear relationship between structures and functions of RECP materials, the high-level and effective characterization technologies and analytic methods are absolutely necessary. Normally, diversiform measurement methods should be used simultaneously to analyze RECP materials clearly from different aspects, such as the phases, structures, morphologies, compositions, properties and performances. Therefore, this review will introduce the features and advantages of different analytic technologies and discuss their significances for the research on RECP materials. We hope that this review will provide valuable suggestions for researchers to promote the further research and development of RECP functional materials in the future.
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BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade tumor that typically does not metastasize but often recurs. Fibrosarcomatous DFSP (FS-DFSP) is associated with a substantially higher rate of metastasis and a poorer prognosis. OBJECTIVE: This study sought to investigate the epidemiological, histopathological, and clinical characteristics of DFSP, especially with a particular focus on FS-DFSP. MATERIALS AND METHODS: Clinical data from 254 patients treated between January 1999 and July 2018 were retrospectively reviewed. Endpoints of the study were the incidence of significant disease-related clinical events. RESULTS: Follow-up data from 211 patients were available for analysis, with a median follow-up time of 38 months (range: 1-196 months). The 5-year recurrence-free survival rate of patients underwent wide-local excision (WLE) was 97.1%. Patients underwent WLE exhibited a significantly decreased recurrence rate relative to patients treated through local excision (2.9% vs 37.7%; p < .001). Fibrosarcomatous DFSP had significantly higher rates of distant metastasis (66.7% [n = 4] vs 2.0% [n = 4]; p < .001) and long-term mortality (50.0% [n = 3] vs 1.5% [n = 3]; p < .001), compared with classical DFSP (C-DFSP). CONCLUSION: Wide-local excision is an effective means of reducing DFSP recurrence. Rates of metastasis are higher for FS-DFSP than for C-DFSP, with the former having significantly poorer outcomes.
Subject(s)
Dermatofibrosarcoma/therapy , Dermatologic Surgical Procedures/methods , Neoplasm Recurrence, Local/epidemiology , Skin Neoplasms/therapy , Adolescent , Adult , Aged , Chemotherapy, Adjuvant/methods , Child , Dermatofibrosarcoma/diagnosis , Dermatofibrosarcoma/mortality , Dermatofibrosarcoma/secondary , Disease-Free Survival , Female , Follow-Up Studies , Humans , Incidence , Kaplan-Meier Estimate , Male , Margins of Excision , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Prognosis , Retrospective Studies , Skin/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/mortality , Skin Neoplasms/secondary , Survival Rate , Young AdultABSTRACT
High-grade myofibroblastic sarcoma (HGMS) is a rare cancer that has high recurrence and metastatic rates. Here, we report the first case of HGMS originating from the pleura. Based on the findings of pleural biopsy, pathological examination and immunohistochemical staining, grade III myofibroblastic sarcoma (MS) was diagnosed. The patient underwent eight cycles of chemotherapy (epirubicin and ifosfamide), followed by radiotherapy. As of May 2020, the patient had been followed for six months and no tumor progression had occurred. KEY POINTS: This is the first report of high-grade myofibroblastic sarcoma originating from the pleura. The patient was treated via nonsurgical strategies, including chemotherapy and radiotherapy.
Subject(s)
Pleura/physiopathology , Sarcoma/pathology , Female , Humans , Middle Aged , Neoplasm GradingABSTRACT
To understand the effects of thermal shock on microcrack propagation and permeability in coal, thermal shock tests were conducted on coal specimens by using a constant temperature drying oven (105 °C) and a SLX program controlled cryogenic tank. The growth and propagation of microcracks were measured with computer tomography (CT) scanning and scanning electron microscope (SEM) tests. Results showed that thermal shocks improved the permeability of coal significantly. Notably, the permeability of coal after thermal shocks increased from 211.31% to 368.99% and was positively correlated with temperature difference. CT scanning images revealed that thermal shocks increased the crack number, crack volume and crack width as well as smoothened and widened the gas flow paths, thereby enhancing coal permeability. Moreover, SEM images showed that heating-cooling shocks created more new microcracks, forming more complex crack propagation paths and better connectivity among microcracks in coal compared to cooling shocks. We proposed a crack propagation criterion for coal to explain the mechanism of crack failure and propagation during thermal shocks. Our experiment results and theoretical analysis indicate that the heating-cooling shock is more effective in damaging and breaking coal than the cooling shock. Thus, it can be used as an alternative approach to enhance coal permeability in the production of coalbed methane (CBM).
Subject(s)
Coal , Mechanical Phenomena , Temperature , Materials Testing , Permeability , Time Factors , Tomography, X-Ray ComputedABSTRACT
Enynes are important synthetic intermediates that are also found in a variety of natural products and other biologically relevant molecules. The most atom economical synthetic route to enynes is via the direct coupling of readily available terminal alkyne precursors. Towards this goal, we demonstrate the formation of 1,3-enynes from terminal alkynes facilitated by a reduced ZrIV/Co-I heterobimetallic complex. An intermediate is trapped as a tBuNC adduct, revealing that bimetallic activation of the terminal C-H bond of the alkyne is an essential mechanistic step.
Subject(s)
Alkenes/chemistry , Alkynes/chemistry , Cobalt/chemistry , Zirconium/chemistry , Catalysis , Dimerization , Molecular Structure , StereoisomerismABSTRACT
The reactivity of the terminal zirconium(iv) oxo complex, O[triple bond, length as m-dash]Zr(MesNPiPr2)3CoCN t Bu (2), is explored, revealing unique redox activity imparted by the pendent redox active cobalt(i) center. Oxo complex 2 can be chemically reduced using Na/Hg or Ph3C⢠to afford the ZrIV/Co0 complexes [(µ-Na)OZr(MesNPiPr2)3CoCN t Bu]2 (3) and Ph3COZr(MesNPiPr2)3CoCN t Bu (4), respectively. Based on the cyclic voltammogram of 2, Ph3Ë should not be sufficiently reducing to achieve the chemical reduction of 2, but sufficient driving force for the reaction is provided by the nucleophilicity of the terminal oxo fragment and its affinity to bind Ph3C+. Accordingly, 2 reacts readily with [Ph3C][BPh4] and Ph3CCl to afford [Ph3COZr(MesNPiPr2)3CoCN t Bu][BPh4] ([5][BPh4]) and Ph3COZr(MesNPiPr2)3CoCl (6), respectively. The chemical oxidation of 2 is also investigated, revealing that oxidation of 2 is accompanied by immediate hydrogen atom abstraction to afford the hydroxide complex [HOZr(MesNPiPr2)3CoCN t Bu]+ ([9]+). Thus it is posited that the transient [OZr(MesNPiPr2)3CoCN t Bu]+ [2]+ cation generated upon oxidation combines the basicity of a nucleophilic early metal oxo fragment with the oxidizing power of the appended cobalt center to facilitate H-atom abstraction.
ABSTRACT
Renal cell carcinoma (RCC) with anaplastic lymphoma kinase (ALK) rearrangement is rare, and the genetic profiles of the tumor have not been elucidated. Here, we report a case with recurrent papillary RCC and lung metastasis after nephrectomy for nearly 7 years. The patient first received sunitinib, whereas the drug toxicity was intolerable. Combined Immunohistology (IHC) and fluorescence in situ hybridization (FISH) revealed the patient has an ALK rearrangement, and the patient then was treated with crizotinib. The patient had good tolerance, and a partial response in the target lesions was achieved. In order to further understand the benefit of crizotinib in ALK-rearranged RCC, the patient was detected with whole exome sequencing (WES) to study her genetic profiles. Compared those of RCC cases without ALK rearrangement (nALK-RCC), the patient and nine RCC cases with ALK rearrangement (ALK-RCC) revealed unique genetic characteristics: 1) The common mutations that occurred in RCC were not found in ALK-RCC.; 2) A total of 11 co-existing mutations in ALK-RCC were found, and they occurred in nALK-RCC at a relatively low frequency. DNMT3A mutations were concurrent with ALK fusions in our case. These findings indicated a different genetic alteration pattern of ALK-RCC from nALK-RCC. Our case demonstrated the efficacy of crizotinib in an RCC patient with ALK rearrangement.
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Oxygen reduction is a critical half reaction in renewable fuel cell development and a key step in the development of aerobic oxidation reactions. Herein, we report rapid two-electron O2 reduction by a d0 ZrIV center with an appended redox-active Co-I site serving as an electron reservoir. The early/late heterobimetallic Zr/Co complex (THF)Zr(MesNP iPr2)3CoCN tBu (1) reacts readily with O2 and O atom transfer reagents to generate reactive oxygenated species including terminal peroxo and oxo complexes, (O2)Zr(MesNP iPr2)3CoCN tBu (2) and O≡Zr(MesNP iPr2)3CoCN tBu (3). The bimetallic Zr/Co complex provides a new cooperative synthetic pathway to promote multielectron redox processes such as oxygen reduction, with each metal playing a distinct role as a substrate binding site or redox mediator.