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1.
Proc Natl Acad Sci U S A ; 121(8): e2319696121, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38346181

RESUMO

The phylogeny and divergence timing of the Neoavian radiation remain controversial despite recent progress. We analyzed the genomes of 124 species across all Neoavian orders, using data from 25,460 loci spanning four DNA classes, including 5,756 coding sequences, 12,449 conserved nonexonic elements, 4,871 introns, and 2,384 intergenic segments. We conducted a comprehensive sensitivity analysis to account for the heterogeneity across different DNA classes, leading to an optimal tree of Neoaves with high resolution. This phylogeny features a novel Neoavian dichotomy comprising two monophyletic clades: a previously recognized Telluraves (land birds) and a newly circumscribed Aquaterraves (waterbirds and relatives). Molecular dating analyses with 20 fossil calibrations indicate that the diversification of modern birds began in the Late Cretaceous and underwent a constant and steady radiation across the KPg boundary, concurrent with the rise of angiosperms as well as other major Cenozoic animal groups including placental and multituberculate mammals. The KPg catastrophe had a limited impact on avian evolution compared to the Paleocene-Eocene Thermal Maximum, which triggered a rapid diversification of seabirds. Our findings suggest that the evolution of modern birds followed a slow process of gradualism rather than a rapid process of punctuated equilibrium, with limited interruption by the KPg catastrophe. This study places bird evolution into a new context within vertebrates, with ramifications for the evolution of the Earth's biota.


Assuntos
Fósseis , Magnoliopsida , Gravidez , Feminino , Animais , Magnoliopsida/genética , Placenta , Filogenia , Aves/genética , Mamíferos/genética , DNA Mitocondrial/genética , Evolução Biológica
2.
Proc Natl Acad Sci U S A ; 119(15): e2119217119, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35344399

RESUMO

SignificanceOwls, with their largely nocturnal habits, contrast strikingly with the vast majority of diurnal birds. A new spectacular late Miocene owl skeleton from China unexpectedly preserves the oldest evidence for daytime behavior in owls. The extinct owl is a member of the clade Surniini, which contains most living diurnal owl species. Analysis of the preserved eye bones documents them as consistent with diurnal birds, and phylogenetically constrained character mapping coincides with a reconstruction of an early evolutionary reversal away from nocturnal habits in this owl group. These results support a potential Miocene origin of nonnocturnal habits in a globally distributed owl group, which may be linked to steppe habitat expansion and climatic cooling in the late Miocene.


Assuntos
Evolução Biológica , Estrigiformes , Animais , Comportamento Animal , China , Ritmo Circadiano , Ecossistema , Fósseis , Hábitos
3.
J Anat ; 244(4): 541-556, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38055909

RESUMO

Vocal production in birds has been the target of considerable research that mostly has focused on phylogenetically well-nested songbirds. Anatomical descriptions and recordings of many non-songbirds have often only focused on a single ontogenetic stage or sex. While basic morphology of the vocal organ (syrinx) of ostrich (Palaeognathae, Struthio camelus) has been known since the 1800s, descriptions of its vocal repertoire and syrinx anatomy since then have been incomplete or inconsistent. New toolkits now enable detailed qualitative description of internal anatomy and meristic data and allow it to be compared to vocal production. Here we describe the anatomy of the syrinx in Struthio camelus for three post-hatching ontogenetic stages and both an adult male and female utilizing dissection and contrast enhanced X-ray computed tomography (diceCT). We find changes in ring geometry and spacing through ontogeny as well as lateral labia thickness. We document a small unpaired, midline, cartilaginous structure, a "pessuliform process" at the tracheobronchial juncture present throughout ontogeny and in both males and females. Investigation of the vocal repertoire of ostriches across ontogeny using a new dataset of 77 recordings led to identification of four vocalizations not previously reported in the literature, including the simultaneous production of a hiss and tonal. We find syrinx morphology largely consistent across ontogeny and in male and female adults. Both are capable of producing long duration tonal calls, but these may be more frequent in male birds. Closed-mouth boom calls remain unique to males. A detailed understanding of diversity in parts of early diverging clades is pivotal in attempting to estimate features of the ancestral syrinx in birds and how avian vocalization evolved.


Assuntos
Aves Canoras , Struthioniformes , Animais , Masculino , Feminino , Struthioniformes/anatomia & histologia , Vocalização Animal , Traqueia/anatomia & histologia , Radiografia
4.
BMC Cancer ; 24(1): 220, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365636

RESUMO

BACKGROUND: Glioblastoma (GBM) is a relatively prevalent primary tumor of the central nervous system in children, characterized by its high malignancy and mortality rates, along with the intricate challenges of achieving complete surgical resection. Recently, an increasing number of studies have focused on the crucial role of super-enhancers (SEs) in the occurrence and development of GBM. This study embarks on the task of evaluating the effectiveness of MZ1, an inhibitor of BRD4 meticulously designed to specifically target SEs, within the intricate framework of GBM. METHODS: The clinical data of GBM patients was sourced from the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the gene expression data of tumor cell lines was derived from the Cancer Cell Line Encyclopedia (CCLE). The impact of MZ1 on GBM was assessed through CCK-8, colony formation assays, EdU incorporation analysis, flow cytometry, and xenograft mouse models. The underlying mechanism was investigated through RNA-seq and ChIP-seq analyses. RESULTS: In this investigation, we made a noteworthy observation that MZ1 exhibited a substantial reduction in the proliferation of GBM cells by effectively degrading BRD4. Additionally, MZ1 displayed a notable capability in inducing significant cell cycle arrest and apoptosis in GBM cells. These findings were in line with our in vitro outcomes. Notably, MZ1 administration resulted in a remarkable decrease in tumor size within the xenograft model with diminished toxicity. Furthermore, on a mechanistic level, the administration of MZ1 resulted in a significant suppression of pivotal genes closely associated with cell cycle regulation and epithelial-mesenchymal transition (EMT). Interestingly, our analysis of RNA-seq and ChIP-seq data unveiled the discovery of a novel prospective oncogene, SDC1, which assumed a pivotal role in the tumorigenesis and progression of GBM. CONCLUSION: In summary, our findings revealed that MZ1 effectively disrupted the aberrant transcriptional regulation of oncogenes in GBM by degradation of BRD4. This positions MZ1 as a promising candidate in the realm of therapeutic options for GBM treatment.


Assuntos
Neoplasias Encefálicas , Proteínas que Contêm Bromodomínio , Glioblastoma , Animais , Criança , Humanos , Camundongos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Proteínas que Contêm Bromodomínio/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Estudos Prospectivos , Sindecana-1/antagonistas & inibidores , Fatores de Transcrição/genética
5.
Environ Sci Technol ; 58(26): 11280-11291, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38898567

RESUMO

Soil antibiotic pollution profoundly influences plant growth and photosynthetic performance, yet the main disturbed processes and the underlying mechanisms remain elusive. This study explored the photosynthetic toxicity of quinolone antibiotics across three generations on rice plants and clarified the mechanisms through experimental and computational studies. Marked variations across antibiotic generations were noted in their impact on rice photosynthesis with the level of inhibition intensifying from the second to the fourth generation. Omics analyses consistently targeted the light reaction phase of photosynthesis as the primary process impacted, emphasizing the particular vulnerability of photosystem II (PS II) to the antibiotic stress, as manifested by significant interruptions in the photon-mediated electron transport and O2 production. PS II center D2 protein (psbD) was identified as the primary target of the tested antibiotics, with the fourth-generation quinolones displaying the highest binding affinity to psbD. A predictive machine learning method was constructed to pinpoint antibiotic substructures that conferred enhanced affinity. As antibiotic generations evolve, the positive contribution of the carbonyl and carboxyl groups on the 4-quinolone core ring in the affinity interaction gradually intensified. This research illuminates the photosynthetic toxicities of antibiotics across generations, offering insights for the risk assessment of antibiotics and highlighting their potential threats to carbon fixation of agroecosystems.


Assuntos
Antibacterianos , Oryza , Fotossíntese , Complexo de Proteína do Fotossistema II , Quinolonas , Oryza/efeitos dos fármacos , Oryza/metabolismo , Fotossíntese/efeitos dos fármacos , Antibacterianos/farmacologia , Complexo de Proteína do Fotossistema II/metabolismo
6.
Sensors (Basel) ; 24(4)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38400287

RESUMO

Accurate calibration between LiDAR and camera sensors is crucial for autonomous driving systems to perceive and understand the environment effectively. Typically, LiDAR-camera extrinsic calibration requires feature alignment and overlapping fields of view. Aligning features from different modalities can be challenging due to noise influence. Therefore, this paper proposes a targetless extrinsic calibration method for monocular cameras and LiDAR sensors that have a non-overlapping field of view. The proposed solution uses pose transformation to establish data association across different modalities. This conversion turns the calibration problem into an optimization problem within a visual SLAM system without requiring overlapping views. To improve performance, line features serve as constraints in visual SLAM. Accurate positions of line segments are obtained by utilizing an extended photometric error optimization method. Moreover, a strategy is proposed for selecting appropriate calibration methods from among several alternative optimization schemes. This adaptive calibration method selection strategy ensures robust calibration performance in urban autonomous driving scenarios with varying lighting and environmental textures while avoiding failures and excessive bias that may result from relying on a single approach.

7.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 393-401, 2024 Jun.
Artigo em Zh | MEDLINE | ID: mdl-38953263

RESUMO

Cardiovascular diseases,such as coronary heart disease (CHD),are the main causes of death in humans.Cardiac rehabilitation with exercise therapy as the core contents is a rehabilitation program specially designed for the patients with cardiovascular diseases,aiming to help the patients improve their physical functions and return to social activities as soon as possible.Active cardiac rehabilitation can not only reduce the morbidity and mortality of CHD and improve the cardiopulmonary function of patients but also reduce the medical and economic burden.This article summarizes the effect of physical function on CHD patients,the current application mode of exercise therapy in cardiac rehabilitation,and the formulation principles of different exercise prescriptions in cardiac rehabilitation,aiming to provide a reference for the application of exercise therapy in CHD patients.


Assuntos
Doença das Coronárias , Terapia por Exercício , Humanos , Terapia por Exercício/métodos , Doença das Coronárias/reabilitação , Doença das Coronárias/prevenção & controle , Doença das Coronárias/terapia , Reabilitação Cardíaca/métodos
8.
Angew Chem Int Ed Engl ; 63(19): e202400764, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38501852

RESUMO

Anion exchange membranes (AEMs) are core components in anion exchange membrane water electrolyzers (AEM-WEs). However, the stability of functional quaternary ammonium cations, especially under high temperatures and harsh alkaline conditions, seriously affects their performance and durability. Herein, we synthesized a 1-methyl-3,3-diphenylquinuclidinium molecular building unit. Density functional theory (DFT) calculations and accelerated aging analysis indicated that the quinine ring structure was exceedingly stable, and the SN2 degradation mechanism dominated. Through acid-catalyzed Friedel-Crafts polymerization, a series of branched poly(aryl-quinuclidinium) (PAQ-x) AEMs with controllable molecular weight and adjustable ion exchange capacity (IEC) were prepared. The stable quinine structure in PAQ-x was verified and retained in the ex situ alkaline stability. Furthermore, the branched polymer structure reduces the swelling rate and water uptake to achieve a tradeoff between dimensional stability and ionic conductivity, significantly improving the membrane's overall performance. Importantly, PAQ-5 was used in non-noble metal-based AEM-WE, achieving a high current density of 8 A cm-2 at 2 V and excellent stability over 2446 h in a gradient constant current test. Based on the excellent alkaline stability of this diaryl-quinuclidinium group, it can be further considered as a multifunctional building unit to create multi-topological polymers for energy conversion devices used in alkaline environments.

9.
Biochem Biophys Res Commun ; 674: 170-182, 2023 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-37423037

RESUMO

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a poor prognosis. The growth of GBM cells depends on the core transcriptional apparatus, thus rendering RNA polymerase (RNA pol) complex as a candidate therapeutic target. The RNA pol II subunit B (POLR2B) gene encodes the second largest subunit of the RNA pol II (RPB2); however, its genomic status and function in GBM remain unclear. Certain GBM data sets in cBioPortal were used for investigating the genomic status and expression of POLR2B in GBM. The function of RPB2 was analyzed following knockdown of POLR2B expression by shRNA in GBM cells. The cell counting kit-8 assay and PI staining were used for cell proliferation and cell cycle analysis. A xenograft mouse model was established to analyze the function of RPB2 in vivo. RNA sequencing was performed to analyze the RPB2-regulated genes. GO and GSEA analyses were applied to investigate the RPB2-regulated gene function and associated pathways. In the present study, the genomic alteration and overexpression of the POLR2B gene was described in glioblastoma. The data indicated that knockdown of POLR2B expression suppressed tumor cell growth of glioblastoma in vitro and in vivo. The analysis further demonstrated the identification of the RPB2-regulated gene sets and highlighted the DNA damage-inducible transcript 4 gene as the downstream target of the POLR2B gene. The present study provides evidence indicating that RPB2 functions as a growth regulator in glioblastoma and could be used as a potential therapeutic target for the treatment of this disease.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Animais , Camundongos , Glioblastoma/patologia , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , Proliferação de Células/genética , Neoplasias Encefálicas/patologia , RNA Interferente Pequeno/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
10.
Opt Express ; 31(14): 23662-23677, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37475446

RESUMO

Reconstructing an object's three-dimensional shape behind a scattering layer with a single exposure is of great significance in real-life applications. However, due to the little information captured by a single exposure while strongly perturbed by the scattering layer and encoded by free-space propagation, existing methods cannot achieve scan-free three-dimensional reconstruction through the scattering layer in macroscopic scenarios using a short acquisition time of seconds. In this paper, we proposed a scan-free time-of-flight-based three-dimensional reconstruction method based on explicitly modeling and inverting the time-of-flight-based scattering light propagation in a non-confocal imaging system. The non-confocal time-of-flight-based scattering imaging model is developed to map the three-dimensional object shape information to the time-resolved measurements, by encoding the three-dimensional object shape into the free-space propagation result and then convolving with the scattering blur kernel derived from the diffusion equation. To solve the inverse problem, a three-dimensional shape reconstruction algorithm consisting of the deconvolution and diffractive wave propagation is developed to invert the effects caused by the scattering diffusion and the free-space propagation, which reshapes the temporal and spatial distribution of scattered signal photons and recovers the object shape information. Experiments on a real scattering imaging system are conducted to demonstrate the effectiveness of the proposed method. The single exposure used in the experiment only takes 3.5 s, which is more than 200 times faster than confocal scanning methods. Experimental results show that the proposed method outperforms existing methods in terms of three-dimensional reconstruction accuracy and imaging limit subjectively and objectively. Even though the signal photons captured by a single exposure are too highly scattered and attenuated to present any valid information in time gating, the proposed method can reconstruct three-dimensional objects located behind the scattering layer of 9.6 transport mean free paths (TMFPs), corresponding to the round-trip scattering length of 19.2 TMFPs.

11.
Sensors (Basel) ; 23(10)2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37430808

RESUMO

Taxis are an important component of the transportation system, and empty taxis represent a significant waste of transportation resources. To alleviate the imbalance between supply and demand and relieve traffic congestion, real-time prediction of taxi trajectories is necessary. Most existing trajectory prediction studies focus on extracting time-series information but do not capture spatial information sufficiently. In this paper, we focus on the construction of an urban network and propose an urban topology-encoding spatiotemporal attention network (UTA) to address destination prediction problems. Firstly, this model discretizes the production and attraction units of transportation, combining them with key nodes in the road network to form an urban topological network. Secondly, GPS records are matched to the urban topological map to construct a topological trajectory, which significantly improves trajectory consistency and endpoint certainty, helping to model destination prediction problems. Thirdly, semantic information concerning surrounding space is attached to effectively mine the spatial dependencies of trajectories. Finally, after the topological encoding of city space and trajectories, this algorithm proposes a topological graph neural network to model the attention calculation with the trajectory context, comprehensively considering the spatiotemporal characteristics of the trajectories and improving prediction accuracy. We solve the prediction problems with the UTA model and also compare it with some other classical models, such as the HMM, RNN, LSTM, and transformer. The results suggest that all the models work well in combination with the proposed urban model (with a rough increase of 2%), while the UTA model is less affected by data sparsity.

12.
Molecules ; 28(10)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37241733

RESUMO

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a non-invasive and effective approach used for cancer treatment, in which phototherapeutic agents are irradiated with an appropriate light source to produce cytotoxic reactive oxygen species (ROS) or heat to ablate cancer cells. Unfortunately, traditional phototherapy lacks a facile imaging method to monitor the therapeutic process and efficiency in real time, usually leading to severe side effects due to high levels of ROS and hyperthermia. To realize precise cancer treatment methods, it is highly desired to develop phototherapeutic agents possessing an imaging ability to evaluate the therapeutic process and efficacy in real time during cancer phototherapy. Recently, a series of self-reporting phototherapeutic agents were reported to monitor PDT and PTT processes by combining optical imaging technologies with phototherapy. Due to the real-time feedback provided by optical imaging technology, therapeutic responses or dynamic changes in the tumor microenvironment could be evaluated in a timely manner, thereby achieving personalized precision treatment and minimizing toxic side effects. In this review, we focus on the advances in the development of self-reporting phototherapeutic agents for a cancer phototherapy evaluation based on optical imaging technology to realize precision cancer treatments. Additionally, we propose the current challenges and future directions of self-reporting agents for precision medicine.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Espécies Reativas de Oxigênio , Fototerapia , Imagem Óptica , Terapia Fototérmica , Nanopartículas/uso terapêutico , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Microambiente Tumoral
13.
Genes Chromosomes Cancer ; 61(1): 50-54, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34553465

RESUMO

Most tumors are sporadic and originated from somatic mutations. Some rare germline mutations cause familial tumors, often involving multiple tissues or organs. Tumors from somatic mosaicism during embryonic development are extremely rare. We describe here a pediatric patient who developed both an ovarian germ cell tumor and systemic mastocytosis. Targeted DNA next-generation sequencing analysis revealed similar genomic changes including the same KIT D816V mutation in both tissues, suggesting a common progenitor cancer cell. The KIT mutated cells are likely from early embryonic development during germ cell migration. A literature search found additional eight similar cases. These diseases are characterized by pediatric-onset, all-female, neoplastic proliferation in both gonad and bone marrow, and a common oncogenic cause, that is, KIT mutation, constituting a clinically and genetically homogenous disease entity. Importantly, the association of germ cell tumors with hematopoietic neoplasms suggests that the primordial germ cells are the primitive hematopoietic stem cells, a much-debated and unsettled question.


Assuntos
Mastocitose Sistêmica/genética , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Ovarianas/genética , Proteínas Proto-Oncogênicas c-kit/genética , Medula Óssea/metabolismo , Medula Óssea/patologia , Pré-Escolar , Feminino , Mutação em Linhagem Germinativa , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Humanos , Mastocitose Sistêmica/metabolismo , Mastocitose Sistêmica/patologia , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-kit/metabolismo
14.
Waste Manag Res ; 41(6): 1102-1113, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36544376

RESUMO

With the advancement of the landfill stabilization process of municipal solid waste, landfill leachate containing a large amount of refractory organic matter is formed. In this study, homogeneous Fenton and heterogeneous Fenton-like (activation by zero valent iron (Fe0), pyrite (FeS2) and magnetite (Fe3O4) as solid iron materials) processes have been compared for the removal of refractory organics from landfill leachate. The removal efficiency of organics in the Fenton process was slightly higher than those in the Fenton-like processes. The removal efficiencies based on total organic carbon, UV absorbance at 254 nm (UV254) and colour number in the Fenton process were as high as 57.42%, 71.63% and 81.03%, respectively. In the Fenton-like processes, the Fe0/H2O2 process achieved 35.74%, 66.24% and 86.29% removal efficiencies, respectively. Moreover, the degradation effect on refractory organic substances proved to be better. In the Fenton-like processes, the activation mechanisms with Fe0 and FeS2 involve the homogeneous activation of Fe2+ in solution and heterogeneous activation of iron oxides produced during the reaction, respectively. With Fe3O4, the activation mechanism is mainly a heterogeneous process involving its intrinsic iron oxide constituents. This study may provide a theoretical basis for the treatment of refractory organics in landfill leachate.


Assuntos
Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Peróxido de Hidrogênio , Ferro , Resíduos Sólidos , Oxirredução
15.
Waste Manag Res ; 41(5): 1004-1013, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36472338

RESUMO

Landfill leachate contains a large amount of refractory organic matter, which will cause harm to the environment if not appropriately treated. In this study, the refractory organic matter in landfill leachate has been treated by in situ electrogenerated H2O2 combined with an Fe0 Fenton-like process, aiming to explore a cleaner and more efficient process for leachate treatment. The results showed that the current, initial pH and oxygen flow rate have significant influences on H2O2 production. The current and oxygen flow rate are positively correlated with H2O2 production, and neutral conditions are more favourable. Under the conditions of a current of 200 mA, an initial pH of 7.0 and an oxygen flow rate of 0.3 L/min, H2O2 production reached 2.81 mM, the current efficiency was close to 80% and the highest removal efficiency of organic matter reached 40.70%. The absorbance at 280 nm (E280) decreased from 0.1669 to 0.1180, and the ratios E240/E420, E250/E365 and E300/E400 in the UV and visible regions changed from 0.7825, 5.4492 and 0.2422 to 1.3135, 7.3745 and 0.2966, respectively. The maximum fluorescence intensities due to humic-like acid and fulvic-like acid substances decreased from 1275 and 1246 to 595.9 and 711.0, respectively. Spectral analysis further showed that the complex structure of refractory organic matter in the landfill leachate was obviously destroyed, and the relative content of humus decreased significantly. This study may provide a theoretical basis for the effective treatment of refractory organic matter in landfill leachate by in situ electrogenerated H2O2 combined with a Fenton-like process.


Assuntos
Peróxido de Hidrogênio , Poluentes Químicos da Água , Peróxido de Hidrogênio/química , Poluentes Químicos da Água/análise , Oxigênio , Solo , Oxirredução
16.
J Am Chem Soc ; 144(34): 15779-15785, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-35976107

RESUMO

Distinct regio- and enantioselectivity control in copper-catalyzed vinylogous and bisvinylogous propargylic substitution has been accomplished by using a novel chiral N,N,P ligand. The developed method provides an efficient and selective approach to an array of highly enantioenriched alkynyl unsaturated carbonyl compounds. Salient features include excellent functional group tolerance and broad substrate scope. The synthetic utility of the developed method is further demonstrated by a gram-scale synthesis and by application to a range of transformations including enantioselective synthesis of unique challenging compounds.


Assuntos
Cobre , Catálise , Cobre/química , Ligantes , Estrutura Molecular , Estereoisomerismo
17.
Biochem Biophys Res Commun ; 604: 63-69, 2022 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-35299072

RESUMO

Neuroblastoma(NB) is a common childhood solid tumor, and most patients in the high-risk group with MYCN gene amplification have a poor prognosis. Inhibition of bromodomain and extra terminal (BET) proteins has shown considerable promise in the investigation of MYCN-driven malignancies in recent years. MZ1 is a novel BET inhibitor that employs proteolytic-targeting chimera (PROTAC) technology for proteasomal degradation of target proteins and has shown excellent effects in some tumors, but its role in neuroblastoma remains poorly understood. Herein, we observed that MZ1 suppressed MYC-amplified NB cell proliferation and normal cell cycle, while simultaneously boosting cell apoptosis. MZ1 also provides a significant therapeutic impact in vivo. Mechanistically, MZ1 exhibits anti-tumor effect in NB cells by suppressing the expression of N-Myc or C-Myc as well as the MAPK signaling pathway. Overall, our data imply that MZ1 might be exploited as a possible therapeutic method for NB therapy.


Assuntos
Proteínas de Ciclo Celular , Dipeptídeos , Compostos Heterocíclicos com 3 Anéis , Proteína Proto-Oncogênica N-Myc , Neuroblastoma , Fatores de Transcrição , Proteínas de Ciclo Celular/antagonistas & inibidores , Linhagem Celular Tumoral , Criança , Dipeptídeos/farmacologia , Regulação Neoplásica da Expressão Gênica , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Neuroblastoma/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo
18.
J Anat ; 240(4): 627-638, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34854094

RESUMO

The globally distributed extinct clade Enantiornithes comprises the most diverse early radiation of birds in the Mesozoic with species exhibiting a wide range of body sizes, morphologies, and ecologies. The fossil of a new enantiornithine bird, Brevirostruavis macrohyoideus gen. et sp. nov., from the Lower Cretaceous Jiufotang Formation in Liaoning Province, northeastern China, preserves a few important skeletal features previously unknown among early stem and extant birds, including an extremely elongate bony hyoid element (only slightly shorter than the skull), combined with a short cranial rostrum. The long hyoid provides direct evidence for the evolution of specialized feeding in this extinct species, and appears similar to the highly mobile tongue that is mobilized by the paired epibranchials present in living hummingbirds, honeyeaters, and woodpeckers. The likely linkage between food acquisition and tongue protrusion might have been a key factor in the independent evolution of particularly elongate hyobranchials in early birds.


Assuntos
Evolução Biológica , Fósseis , China , Filogenia , Crânio/anatomia & histologia , Língua
19.
Nature ; 538(7626): 502-505, 2016 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-27732575

RESUMO

From complex songs to simple honks, birds produce sounds using a unique vocal organ called the syrinx. Located close to the heart at the tracheobronchial junction, vocal folds or membranes attached to modified mineralized rings vibrate to produce sound. Syringeal components were not thought to commonly enter the fossil record, and the few reported fossilized parts of the syrinx are geologically young (from the Pleistocene and Holocene (approximately 2.5 million years ago to the present)). The only known older syrinx is an Eocene specimen that was not described or illustrated. Data on the relationship between soft tissue structures and syringeal three-dimensional geometry are also exceptionally limited. Here we describe the first remains, to our knowledge, of a fossil syrinx from the Mesozoic Era, which are preserved in three dimensions in a specimen from the Late Cretaceous (approximately 66 to 69 million years ago) of Antarctica. With both cranial and postcranial remains, the new Vegavis iaai specimen is the most complete to be recovered from a part of the radiation of living birds (Aves). Enhanced-contrast X-ray computed tomography (CT) of syrinx structure in twelve extant non-passerine birds, as well as CT imaging of the Vegavis and Eocene syrinxes, informs both the reconstruction of ancestral states in birds and properties of the vocal organ in the extinct species. Fused rings in Vegavis form a well-mineralized pessulus, a derived neognath bird feature, proposed to anchor enlarged vocal folds or labia. Left-right bronchial asymmetry, as seen in Vegavis, is only known in extant birds with two sets of vocal fold sound sources. The new data show the fossilization potential of the avian vocal organ and beg the question why these remains have not been found in other dinosaurs. The lack of other Mesozoic tracheobronchial remains, and the poorly mineralized condition in archosaurian taxa without a syrinx, may indicate that a complex syrinx was a late arising feature in the evolution of birds, well after the origin of flight and respiratory innovations.


Assuntos
Estruturas Animais/anatomia & histologia , Aves/anatomia & histologia , Fósseis , Vocalização Animal , Animais , Regiões Antárticas , Evolução Biológica , Dinossauros , Extinção Biológica , Crânio/anatomia & histologia
20.
Proc Natl Acad Sci U S A ; 116(49): 24696-24706, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31740590

RESUMO

The avian predentary is a small skeletal structure located rostral to the paired dentaries found only in Mesozoic ornithuromorphs. The evolution and function of this enigmatic element is unknown. Skeletal tissues forming the predentary and the lower jaws in the basal ornithuromorph Yanornis martini are identified using computed-tomography, scanning electron microscopy, and histology. On the basis of these data, we propose hypotheses for the development, structure, and function of this element. The predentary is composed of trabecular bone. The convex caudal surface articulates with rostromedial concavities on the dentaries. These articular surfaces are covered by cartilage, which on the dentaries is divided into 3 discrete patches: 1 rostral articular cartilage and 2 symphyseal cartilages. The mechanobiology of avian cartilage suggests both compression and kinesis were present at the predentary-dentary joint, therefore suggesting a yet unknown form of avian cranial kinesis. Ontogenetic processes of skeletal formation occurring within extant taxa do not suggest the predentary originates within the dentaries, nor Meckel's cartilage. We hypothesize that the predentary is a biomechanically induced sesamoid that arose within the soft connective tissues located rostral to the dentaries. The mandibular canal hosting the alveolar nerve suggests that the dentary teeth and predentary of Yanornis were proprioceptive. This whole system may have increased foraging efficiency. The Mesozoic avian predentary apparently coevolved with an edentulous portion of the premaxilla, representing a unique kinetic morphotype that combined teeth with a small functional beak and persisted successfully for ∼60 million years.


Assuntos
Bico/anatomia & histologia , Aves/fisiologia , Dinossauros/anatomia & histologia , Cinese/fisiologia , Crânio/anatomia & histologia , Animais , Bico/fisiologia , Evolução Biológica , Aves/anatomia & histologia , Dinossauros/fisiologia , Fósseis/anatomia & histologia , Crânio/fisiologia
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