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1.
Dalton Trans ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34590650

RESUMO

Structural stability and rapid charge-discharge capability of electrode materials are required for high performance lithium-ion batteries (LIBs). The materials derived from polyoxometalates (POMs) show special advantages in inhibiting capacity attenuation, and good dispersion or combination of POMs with metal-organic frameworks (MOFs) is an important method to obtain high activity anode composites for LIBs. In this study, a uniform MoO2/MoS2 heterostructure with surface supported carbon (C-MoO2/MoS2) was successfully fabricated from a [Cu2(BTC)4/3(H2O)2]6[H3PMo12O40] precursor, which showed not only the designed octahedral morphology but also fast charge transfer, long working life, and high rate performance. Superior reversible lithium storage capacity of 1047 mA h g-1 after 300 cycles was obtained at 1 A g-1. Even after 700 cycles at 5 A g-1, the discharge specific capacity of 646 mA h g-1 was maintained, and rate capability of 610 mA h g-1 could be achieved at 10 A g-1. The high capacitive contribution could be explained by the relatively large specific surface area of porous C-MoO2/MoS2, which was mainly caused by the supported carbon network and MoS2 nanosheets, resulting in fast lithiation/delithiation processes.

2.
Nanoscale ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34545898

RESUMO

For the design of atom-precise copper nanoclusters, besides the exploration of their aesthetic cage-like architectures, their structural modulation and potential applications are being extensively explored. Herein, an atom-precise 20-core copper(I)-alkynyl nanocluster (UJN-Cu20) protected by ethinyloestradiol ligands issynthesized. By virtue of outer-shell hydroxyl groups, UJN-Cu20 could be uniformly modified on the surface of TiO2 nanosheets via hydrogen bonding interactions, thus forming an efficient nanocomposite photocatalyst for hydrogen evolution. By constructing a Z-scheme heterojunction, the photocatalytic hydrogen evolution activity of the nanocomposite (13 mmol g-1 h-1) significantly improved as compared to that of TiO2 nanosheets (0.4 mmol g-1 h-1). As a narrow bandgap cocatalyst, UJN-Cu20 is confirmed to effectively inhibit the electron-hole recombination on the surface of the TiO2 nanosheet, which provides a new concept for the design of copper cluster-assisted effective photocatalysts.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34387026

RESUMO

The exploration of novel systems for the electrochemical CO2 reduction reaction (CO2 RR) for the production of hydrocarbons like CH4 remains a giant challenge. Well-designed electrocatalysts with advantages like proton generation/transferring and intermediate-fixating for efficient CO2 RR are much preferred yet largely unexplored. In this work, a kind of Cu-porphyrin-based large-scale (≈1.5 µm) and ultrathin nanosheet (≈5 nm) has been successfully applied in electrochemical CO2 RR. It exhibits a superior FE CH 4 of 70 % with a high current density (-183.0 mA cm-2 ) at -1.6 V under rarely reported neutral conditions and maintains FE CH 4 >51 % over a wide potential range (-1.5 to -1.7 V) in a flow cell. The high performance can be attributed to the construction of numerous hydrogen-bonding networks through the integration of diaminotriazine with Cu-porphyrin, which is beneficial for proton migration and intermediate stabilization, as supported by DFT calculations. This work paves a new way in exploring hydrogen-bonding-based materials as efficient CO2 RR catalysts.

4.
Nat Commun ; 12(1): 4626, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330913

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ an RNAi-based in vivo functional genomics platform to determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, we identify protein arginine methyltransferase 1 (PRMT1) as a critical dependency required for PDAC maintenance. Genetic and pharmacological studies validate the role of PRMT1 in maintaining PDAC growth. Mechanistically, using proteomic and transcriptomic analyses, we demonstrate that global inhibition of asymmetric arginine methylation impairs RNA metabolism, which includes RNA splicing, alternative polyadenylation, and transcription termination. This triggers a robust downregulation of multiple pathways involved in the DNA damage response, thereby promoting genomic instability and inhibiting tumor growth. Taken together, our data support PRMT1 as a compelling target in PDAC and informs a mechanism-based translational strategy for future therapeutic development.Statement of significancePDAC is a highly lethal cancer with limited therapeutic options. This study identified and characterized PRMT1-dependent regulation of RNA metabolism and coordination of key cellular processes required for PDAC tumor growth, defining a mechanism-based translational hypothesis for PRMT1 inhibitors.


Assuntos
Carcinoma Ductal Pancreático/genética , Dano ao DNA , Neoplasias Pancreáticas/genética , Proteína-Arginina N-Metiltransferases/genética , RNA/genética , Proteínas Repressoras/genética , Animais , Biocatálise/efeitos dos fármacos , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/prevenção & controle , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/prevenção & controle , Proteína-Arginina N-Metiltransferases/metabolismo , RNA/metabolismo , Interferência de RNA , Proteínas Repressoras/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
5.
BMC Microbiol ; 21(1): 179, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34126927

RESUMO

BACKGROUND: Bacterial community play a key role in environmental and ecological processes in river ecosystems. Rivers are used as receiving body for treated and untreated urban wastewaters that brings high loads of sewage and excrement bacteria. However, little is known about the bacterial community structure and functional files in the rivers around the eutrophic Chaohu Lake, the fifth largest freshwater lake in China, has been subjected to severe eutrophication and cyanobacterial blooms over the past few decades. Therefore, understanding the taxonomic and functional compositions of bacterial communities in the river will contribute to understanding aquatic microbial ecology. The main aims were to (1) examine the structure of bacterial communities and functional profiles in this system; (2) find the environmental factors of bacterial community variations. RESULTS: We studied 88 sites at rivers in the Chaohu Lake basin, and determined bacterial communities using Illumina Miseq sequencing of the 16 S rRNA gene, and predicted functional profiles using PICRUSt2. A total of 3,390,497 bacterial 16 S rRNA gene sequences were obtained, representing 17 phyla, and 424 genera; The dominant phyla present in all samples were Bacteroidetes (1.4-82.50 %), followed by Proteobacteria (12.6-97.30 %), Actinobacteria (0.1-17.20 %). Flavobacterium was the most numerous genera, and accounted for 0.12-80.34 % of assigned 16 S reads, followed by Acinetobacter (0.33-49.28 %). Other dominant bacterial genera including Massilia (0.06-25.40 %), Psychrobacter (0-36.23 %), Chryseobacterium (0.01-22.86 %), Brevundimonas (0.01-12.82 %), Pseudomonas (0-59.73 %), Duganella (0.08-23.37 %), Unidentified Micrococcaceae (0-8.49 %). The functional profiles of the bacterial populations indicated an relation with many human diseases, including infectious diseases. Overall results, using the ß diversity measures, coupled with heatmap and RDA showed that there were spatial variations in the bacterial community composition at river sites, and Chemical oxygen demand (CODMn) and (NH4+ )were the dominant environmental drivers affecting the bacterial community variance. CONCLUSIONS: The high proportion of the opportunistic pathogens (Acinetobacter, Massilia, Brevundimonas) indicated that the discharge of sewage without adequate treatment into the rivers around Chaohu Lake. We propose that these bacteria could be more effective bioindicators for long-term sewage monitoring in eutrophic lakes.

6.
Org Biomol Chem ; 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34060570

RESUMO

In recent years, transition-metal-catalyzed tandem cyclization reactions of alkynes, especially those involving a metal carbene intermediate, have received worthwhile interest, as this type of reaction does not require the use of risky and potentially explosive diazo compounds as starting materials for carbene generation. A significant and general strategy for the stereospecific synthesis of 5-membered cycles is Nazarov cyclization based on the 4π-conrotatory electrocyclization of a conjugated pentadienyl cation to afford a cyclopentenyl cation. In this review, we introduce an overview of recent advances in the transition-metal-catalyzed Nazarov cyclization of alkynes via a metal carbene intermediate, and categorize these reactions according to the structure of the metal carbene. Our aim is to accelerate advancements in this enchanting area of research.

7.
Infect Dis Poverty ; 10(1): 78, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34034826

RESUMO

BACKGROUND: PTB is an infectious disease, which not only seriously affects people's health, but also causes a heavier disease economic burden on patients. At present, reform of the medical insurance payment can be an effective method to control medical expenses. Therefore, our study is to explore the compensation mechanism for pulmonary tuberculosis (PTB) patients with a full period of treatment, to alleviate the financial burden of PTB patients and provide a reference and basis for the reform of PTB payment methods in other regions and countries. METHODS: The quantitative data of PTB patients was collected from the first half of 2015 to the first half of 2018 in Dehui Tuberculosis Hospital in Jilin Province, and medical records of PTB patients registered in the first half of 2018 (n = 100) from the hospital was randomly selected. Descriptive analysis of these quantitative data summarized the number, cost, medication and compliance. Semi-structured in depth interviews with policymakers and physicians were conducted to understand the impact of interventions and its causes. RESULTS: After implementation of the compensation mechanism, the number of PTB patient visits in 2018 was increased by 14.2%, average medical costs for outpatients and inpatients were significantly reduced by 31.8% and 47.0%, respectively, and the auxiliary medication costs was reduced by 36.5%. Moreover, the hospital carried out standardized management of tuberculosis, and the patient compliance was very high, reaching almost 90%. CONCLUSIONS: The capitation compensation mechanism with a full period of treatment was a suitable payment method for PTB, and it is worthy of promotion and experimentation. In addition, the model improved patient compliance and reduced the possibility of drug-resistant PTB. However, due to the short implementation time of the model in the pilot areas, the effect remains to be further observed and demonstrated.

8.
Theriogenology ; 166: 83-89, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33711650

RESUMO

Sebastes schlegelii is a typical viviparous teleost with six months sperm storage duration from November to April. In this study, spermatozoa morphological and physiological characteristics and sperm location in the female ovary were investigated by electron microscopy, computer-assisted sperm analyzer and histologic analysis, respectively. During copulation, we observed that spermatozoa in the testis had mature structure with rod-shaped head, a short midpiece, and a long flagellum. And further verified sperm swam freely at a high speed in the ovary fluid. After copulation, we only found swimming sperm in the ovary fluid at the early storage stage (November to December) and the majority of sperm were scattered randomly in the ovary cavity and partially concentrated in the crypt between the oocyte and stalk of follicle. Thereafter, the ovarian epithelium around the oocytes proliferated rapidly and wrapping spermatozoa outside of the follicular layer and formed a lot of crypts outside of the follicular layer which served as the sperm storage site until fertilization. The present findings would be useful for further understanding the mechanism of long-term sperm storage in viviparous teleost.


Assuntos
Perciformes , Maturação do Esperma , Animais , Copulação , Feminino , Masculino , Ovário , Espermatozoides
9.
Ecotoxicol Environ Saf ; 213: 112069, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33631636

RESUMO

Anthropogenic disturbances, such as pollution discharge and damming, can lead to a global decline in biodiversity in aquatic ecosystems. However, how such disturbances affect microbial community composition and function remains poorly understood. In November 2019, we explored bacterial diversity, community composition and metabolic function in Lake Tianmuhu, China, and in its upstream dammed river, using Illumina MiSeq sequencing and Biolog EcoPlate method based on carbon source utilization. Our results revealed higher variations in bacterial α- and ß-diversity in the dammed river ecosystem than in the lake ecosystem. In addition, the dammed river and lake ecosystems were significantly different in bacterial community compositions and metabolic structures. No significant relationship between species richness and functional (metabolic) diversity was observed in this study. The site that was most impacted by domestic wastewater had the lowest taxonomic diversity but highest metabolic capacity and activity, suggesting that community composition rather than species diversity is more important in determining ecosystem functioning. Overall, our findings indicate that anthropogenic disturbances can significantly alter bacterial community and function, and taxonomic diversity is a weak proxy for ecosystem functioning in a natural freshwater habitat.


Assuntos
Lagos/microbiologia , Microbiota , Águas Residuárias , Microbiologia da Água , Bactérias , Biodiversidade , China , Ecossistema , Rios/química
10.
Angew Chem Int Ed Engl ; 60(18): 10147-10154, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33511739

RESUMO

Multidimensional fabrication of metal-organic frameworks (MOFs) into multilevel channel integrated devices are in high demanded for Li-S separators. Such separators have advantages in pore-engineering that might fulfill requirements such as intercepting the diffusing polysulfides and improving the Li+ /electrolyte transfer in Li-S batteries. However, most reported works focus on the roles of MOFs as ionic sieves for polysulfides while offering limited investigation on the tuning of Li+ transfer across the separators. A photoinduced heat-assisted processing strategy is proposed to fabricate MOFs into multidimensional devices (e.g., hollow/Janus fibers, double-or triple-layer membranes). For the first time, a triple-layer separator with stepped-channels has been designed and demonstrated as a powerful separator with outstanding specific capacity (1365.0 mAh g-1 ) and cycling performance (0.03 % fading per cycle from 100th to 700th cycle), which is superior to single/double-layer and commercial separators. The findings may expedite the development of MOF-based membranes and extend the scope of MOFs in energy-storage technologies.

11.
J Phycol ; 57(1): 379-391, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33150587

RESUMO

Kelps provide critical services for coastal food chains and ecosystem, and they are important food source for some segments of human population. Despite their ecological importance, little is known about long-term impacts of elevated CO2 (eCO2 ) on nutrient metabolites in kelps and the underlying regulation mechanisms. In this study, the kelp Saccharina japonica was cultured in CO2 -enriched coastal mesocosm systems for up to 3 months. We found that, although eCO2 significantly increased the growth rate, carbon concentrations, and C/N ratio of S. japonica, and it had no effect on total nitrogen and protein contents at the end of cultivation period. Meanwhile, it decreased the lipid, magnesium, sodium, and calcium content and changed the amino acid and fatty acid composition. Combining the genome-wide transcriptomic and metabolic evidence, we obtained a system-level understanding of metabolic response of S. japonica to eCO2 . The unique ornithine-urea cycle (OUC) and aspartate-argininosuccinate shunt (AAS), coupled with TCA cycle, balanced the carbon and nitrogen metabolism under eCO2 by providing carbon skeleton for amino acid synthesis and reduced power for nitrogen assimilation. This research provides a major advance in the understanding of kelp nutrient metabolic mechanism in the context of global climate change, and such CO2 -induced shifts in nutritional value may induce changes in the structure and stability of marine trophic webs and affect the quality of human nutrition resources.


Assuntos
Kelp , Dióxido de Carbono , Ecossistema , Nitrogênio , Nutrientes
12.
Bioresour Technol ; 321: 124428, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33272824

RESUMO

Pyropia-processing wastewater (PPW) contains diverse organic nutrients and causes environmental pollution. To explore the nutrient removal efficiency and growth performance of Chlorella sp. on PPW, the cultures were conducted in different culture substrates. Results showed that, after 7 days of incubation, the removal rates of total nitrogen (TN), total phosphorus (TP) and phycobiliprotein (PP) all reached more than 90% by cultivating Chlorella sp. C2 and C. sorokiniana F-275 in PPW. The chemical oxygen demand (COD) removal efficiencies could be over 50%. Meanwhile, the increments of biomass in two tested Chlorella strains were 1.39 and 4.89 times higher than those of BG11 and BBM substrates and the increases in lipid productivity were 1.34 and 10.18- fold, respectively. The C18:3 fatty acid proportions were markedly reduced by 27.89% and 29.10%. These results suggest that Chlorella sp. could efficiently reduce various nutrients in PPW and simultaneously accumulate higher biomass with higher biodiesel characteristics.


Assuntos
Chlorella , Microalgas , Biodegradação Ambiental , Biocombustíveis , Biomassa , Lipídeos , Nitrogênio , Águas Residuárias
13.
J Hazard Mater ; 406: 124685, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33321322

RESUMO

The impacts of micro- and nanoplastics (MNPs) on aquatic animals have been intensively studied; however, the extent and magnitude of potential effects of MNPs on aquatic primary producers are poorly understood. In this study, we quantitatively analyzed the published literature to examine the impacts of MNPs on growth, photosynthesis, pigments, and metabolism of aquatic microalgae. MNPs negatively affected growth of microalgae but usually had a high EC50 (>25 mg/L). However, positively charged MNPs had a much lower EC50 (<1 mg/L). MNPs lowered maximum photochemical efficiency of photosystem II (Fv/Fm) with the effect increasing with concentration of MNPs but diminishing with exposure time, and also reduced chlorophyll a content to enhanced extent with increased MNPs concentration. MNPs induced relatively higher changes in superoxide dismutase (SOD) and malondialdehyde (MDA) levels in marine algae than in freshwater algae. Reactive oxygen species (ROS) levels increased with MNPs concentration and exposure time while SOD levels first increased and then decreased with increasing MNPs concentration. Macrophytes were found to be able to trap MNPs via multiple mechanisms. Future work should focus on the mechanisms behind MNPs impacts on primary productivity and global carbon cycle, and the combined effects of MNPs with other environmental factors.


Assuntos
Microalgas , Poluentes Químicos da Água , Clorofila , Clorofila A , Microplásticos , Fotossíntese , Plásticos , Poluentes Químicos da Água/toxicidade
14.
Talanta ; 221: 121607, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076137

RESUMO

Drug-induced liver injury (DILI) has been a hot issue of public health, owing to its unpredictability and serious harm to public health. Peroxynitrite (ONOO-) is an important biomarker for the assessment and diagnosis of DILI. In this article, based on a kind of rhodamine analogue with a near-infrared (NIR) emission (610 nm-800 nm) and a two-photon absorption cross section (54 GM), a two-photon excited NIR fluorescence probe (NIR-ONOO) for ONOO- was developed. With a high selectivity and a high sensitivity to ONOO-, NIR-ONOO has a linear range for detection of ONOO- from 5.0 × 10-8 to 1.0 × 10-5 M, a good detection limit (15 nM) and a large fluorescence enhancement (340-fold). In addition, NIR-ONOO has been used to monitor ONOO- in cells with satisfactory results. Because of its two-photon excied NIR emission, NIR-ONOO also showed excellent performances for imaging ONOO- including low autofluorescence, stable and persistent fluorescence, and a deep penetration (204 µm). Finally, NIR-ONOO was successfully employed to image ONOO- in inflammatory mouse, drug-induced hepatotoxicity in cells and its remediation. All the results indicated that NIR-ONOO is a powerful chemical tool to image ONOO- and assay drug-induced hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Preparações Farmacêuticas , Animais , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Corantes Fluorescentes , Camundongos , Ácido Peroxinitroso/toxicidade , Fótons
15.
Sci Rep ; 10(1): 20937, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262363

RESUMO

The endoplasmic reticulum (ER) is a complex subcellular organelle composed of diverse structures such as tubules, sheets and tubular matrices. Flaviviruses such as Zika virus (ZIKV) induce reorganization of ER membranes to facilitate viral replication. Here, using 3D super resolution microscopy, ZIKV infection is shown to induce the formation of dense tubular matrices associated with viral replication in the central ER. Viral non-structural proteins NS4B and NS2B associate with replication complexes within the ZIKV-induced tubular matrix and exhibit distinct ER distributions outside this central ER region. Deep neural networks trained to distinguish ZIKV-infected versus mock-infected cells successfully identified ZIKV-induced central ER tubular matrices as a determinant of viral infection. Super resolution microscopy and deep learning are therefore able to identify and localize morphological features of the ER and allow for better understanding of how ER morphology changes due to viral infection.


Assuntos
Aprendizado Profundo , Retículo Endoplasmático/metabolismo , Microscopia/métodos , Zika virus/fisiologia , Encéfalo/patologia , Encéfalo/virologia , Linhagem Celular Tumoral , Retículo Endoplasmático/ultraestrutura , Matriz Extracelular/metabolismo , Humanos , Organoides/metabolismo , Organoides/ultraestrutura , Organoides/virologia , RNA de Cadeia Dupla/metabolismo , Proteínas não Estruturais Virais/metabolismo , Zika virus/ultraestrutura , Infecção por Zika virus/virologia
17.
ACS Nano ; 14(10): 13380-13390, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-32946222

RESUMO

We report on the formation of water-in-water liquid crystal emulsions with permeable colloidal assemblies. Rodlike cellulose nanocrystals (CNC) spontaneously self-assemble into a helical arrangement with the coexistence of nonionic, hydrophilic polyethylene glycol (PEG) and dextran, whereas the two polymer solutions are thermodynamically incompatible. Stable water-in-water emulsions are easily prepared by mixing the respective CNC/polymer solutions, showing micrometric CNC/PEG dispersed droplets and a continuous CNC/dextran phase. With time, the resulting emulsion demixes into an upper, droplet-lean isotropic phase and a bottom, droplet-rich cholesteric phase. Owing to the osmotic pressure gradient between PEG and dextran phases, target transfer of cellulose nanoparticles occurs across the water/water interface to reassemble into a liquid crystal-in-liquid crystal emulsion with global cholesteric organization. The observed structural, optical, and temporal evolution confirm that the colloidal particles in the two immiscible phases experience short-range interactions and form long-range assemblies across the interface.

18.
Cancer Res ; 80(21): 4840-4853, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32928921

RESUMO

Src homology 2 domain-containing phosphatase (SHP2) is a phosphatase that mediates signaling downstream of multiple receptor tyrosine kinases (RTK) and is required for full activation of the MAPK pathway. SHP2 inhibition has demonstrated tumor growth inhibition in RTK-activated cancers in preclinical studies. The long-term effectiveness of tyrosine kinase inhibitors such as the EGFR inhibitor (EGFRi), osimertinib, in non-small cell lung cancer (NSCLC) is limited by acquired resistance. Multiple clinically identified mechanisms underlie resistance to osimertinib, including mutations in EGFR that preclude drug binding as well as EGFR-independent activation of the MAPK pathway through alternate RTK (RTK-bypass). It has also been noted that frequently a tumor from a single patient harbors more than one resistance mechanism, and the plasticity between multiple resistance mechanisms could restrict the effectiveness of therapies targeting a single node of the oncogenic signaling network. Here, we report the discovery of IACS-13909, a specific and potent allosteric inhibitor of SHP2, that suppresses signaling through the MAPK pathway. IACS-13909 potently impeded proliferation of tumors harboring a broad spectrum of activated RTKs as the oncogenic driver. In EGFR-mutant osimertinib-resistant NSCLC models with EGFR-dependent and EGFR-independent resistance mechanisms, IACS-13909, administered as a single agent or in combination with osimertinib, potently suppressed tumor cell proliferation in vitro and caused tumor regression in vivo. Together, our findings provide preclinical evidence for using a SHP2 inhibitor as a therapeutic strategy in acquired EGFRi-resistant NSCLC. SIGNIFICANCE: These findings highlight the discovery of IACS-13909 as a potent, selective inhibitor of SHP2 with drug-like properties, and targeting SHP2 may serve as a therapeutic strategy to overcome tumor resistance to osimertinib.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Experimentais/patologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Acrilamidas/farmacologia , Compostos de Anilina/farmacologia , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Mutação , Neoplasias Experimentais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Ther Adv Hematol ; 11: 2040620720958538, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32994912

RESUMO

Background: Primary lymphoma of bone (PLB) is an extremely rare malignancy arising in the skeletal system. There is no consensus over the best definition of PLB. Most of the published articles are single-institutional retrospective studies with a limited sample size. The rarity of PLB and discrepancies on diagnostic criteria has resulted in a vague understanding of PLB. Methods: We retrospectively analyzed the clinical characteristics and prognostic factors of 2558 PLB patients who were registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2016. Survival rates were calculated using the Kaplan-Meier method. The effects of various factors on survival outcomes were analyzed by using the log-rank test. Univariate and multivariate analyses were conducted by using the Cox proportional hazards model to determine independent prognostic factors. Results: The median follow-up time of all eligible patients was 58 months. There seemed no sex preponderance in PLB incidence. The most involved sites are axial skeletons. The most common histological subtype was diffuse large B-cell lymphoma. The 3-, 5-, 10-, and 20-year overall survival (OS) rates were 70.70%, 65.70%, 54.40% and 39.50%, respectively. PLB patients whose primary tumor sites were appendicular and craniofacial skeletons had a significant survival advantage [hazard ratio (HR) = 0.694, 95% confidence interval (CI) 0.552-0.872; HR = 0.729, 95% CI 0.597-0.889, respectively] over those with axial skeletons as primary tumor sites. Patients with Hodgkin lymphoma, non-Hodgkin lymphoma (NHL)-mature B-cell lymphoma, and NHL-precursor-cell lymphoblastic lymphoma also had a significant OS advantage (HR = 0.392, 95% CI 0.200-0.771; HR = 0.826, 95% CI 0.700-0.973; and HR = 0.453, 95% CI 0.223-0.923, respectively). Patients with Ann Arbor stage III-IV at diagnosis were at higher risk of death than those with stage I-II (HR = 1.348, 95% CI 1.107-1.641). Chemotherapy was an independent favorable prognostic factor (HR = 0.734, 95% CI 0.605-0.890). Conclusions: Primary anatomic site, histology type, higher Ann Arbor stage and chemotherapy were independent prognostic factors. Chemotherapy played a pivotal role in PLB treatment.

20.
Water Res ; 183: 116075, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32745673

RESUMO

Cyanobacterial blooms change benthic nitrogen (N) cycling in eutrophic lake ecosystems by affecting organic carbon (OC) delivery and changing in nutrients availability. Denitrification, anaerobic ammonium oxidation (anammox), and dissimilatory nitrate reduction to ammonium (DNRA) are critical dissimilatory nitrate reduction pathways that determine N removal and N recycling in aquatic environments. A mechanistic understanding of the influence of algal accumulations on partitioning among these pathways is currently lacking. In the present study, a manipulative experiment in aquarium tanks was conducted to determine the response of dissimilatory nitrate reduction pathways to changes in algal biomass, and the interactive effects of OC and nitrate. Potential dinitrogen (N2) production and DNRA rates, and related functional gene abundances were determined during incubation of 3-4 weeks. The results indicated that high algal biomass promoted DNRA but not N2 production. The concentrations of dissolved organic carbon were the primary factor affecting DNRA rates. Low nitrate availability limited N2 production rates in treatments with algal pellets and without nitrate addition. Meanwhile, the AOAamoA gene abundance was significantly correlated with the nrfA and nirS gene abundances, suggesting that coupled nitrification-denitrification/DNRA was prevalent. Partitioning between N2 production and DNRA was positively correlated with the ratios of dissolved organic carbon to nitrate. Correspondingly, in Lake Taihu during summer to fall, the relatively high organic carbon/nitrate might favorably facilitate DNRA over denitrification, subsequently sustaining cyanobacterial blooms.


Assuntos
Compostos de Amônio , Desnitrificação , Ecossistema , Lagos , Nitratos/análise , Nitrogênio
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