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1.
Brief Bioinform ; 24(6)2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37985457

RESUMO

Single-cell RNA-sequencing (scRNA-seq) has emerged as a powerful technique for studying gene expression patterns at the single-cell level. Inferring gene regulatory networks (GRNs) from scRNA-seq data provides insight into cellular phenotypes from the genomic level. However, the high sparsity, noise and dropout events inherent in scRNA-seq data present challenges for GRN inference. In recent years, the dramatic increase in data on experimentally validated transcription factors binding to DNA has made it possible to infer GRNs by supervised methods. In this study, we address the problem of GRN inference by framing it as a graph link prediction task. In this paper, we propose a novel framework called GNNLink, which leverages known GRNs to deduce the potential regulatory interdependencies between genes. First, we preprocess the raw scRNA-seq data. Then, we introduce a graph convolutional network-based interaction graph encoder to effectively refine gene features by capturing interdependencies between nodes in the network. Finally, the inference of GRN is obtained by performing matrix completion operation on node features. The features obtained from model training can be applied to downstream tasks such as measuring similarity and inferring causality between gene pairs. To evaluate the performance of GNNLink, we compare it with six existing GRN reconstruction methods using seven scRNA-seq datasets. These datasets encompass diverse ground truth networks, including functional interaction networks, Loss of Function/Gain of Function data, non-specific ChIP-seq data and cell-type-specific ChIP-seq data. Our experimental results demonstrate that GNNLink achieves comparable or superior performance across these datasets, showcasing its robustness and accuracy. Furthermore, we observe consistent performance across datasets of varying scales. For reproducibility, we provide the data and source code of GNNLink on our GitHub repository: https://github.com/sdesignates/GNNLink.


Assuntos
Regulação da Expressão Gênica , Análise da Expressão Gênica de Célula Única , Reprodutibilidade dos Testes , Redes Neurais de Computação , Redes Reguladoras de Genes , Perfilação da Expressão Gênica , Análise de Sequência de RNA/métodos
2.
Carcinogenesis ; 45(6): 409-423, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38366384

RESUMO

In recent decades, considerable evidence has emerged indicating the involvement of tRNA-derived fragments (tRFs) in cancer progression through various mechanisms. However, the biological effects and mechanisms of tRFs in lung adenocarcinoma (LUAD) remain unclear. In this study, we screen out tRF-29-79, a 5'-tRF derived from tRNAGlyGCC, through profiling the tRF expressions in three pairs of LUAD tissues. We show that tRF-29-79 is downregulated in LUAD and downregulation of tRF-29-79 is associated with poorer prognosis. In vivo and in vitro assay reveal that tRF-29-79 inhibits proliferation, migration and invasion of LUAD cells. Mechanistically, we discovered that tRF-29-79 interacts with the RNA-binding protein PTBP1 and facilitates the transportation of PTBP1 from nucleus to cytoplasm, which regulates alternative splicing in the 3' untranslated region (UTR) of SLC1A5 pre-mRNA. Given that SLC1A5 is a core transporter of glutamine, we proved that tRF-29-79 mediate glutamine metabolism of LUAD through affecting the stability of SLC1A5 mRNA, thus exerts its anticancer function. In summary, our findings uncover the novel mechanism that tRF-29-79 participates in glutamine metabolism through interacting with PTBP1 and regulating alternative splicing in the 3' UTR of SLC1A5 pre-mRNA.


Assuntos
Adenocarcinoma de Pulmão , Sistema ASC de Transporte de Aminoácidos , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas , Neoplasias Pulmonares , Proteína de Ligação a Regiões Ricas em Polipirimidinas , Humanos , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Sistema ASC de Transporte de Aminoácidos/metabolismo , Sistema ASC de Transporte de Aminoácidos/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Camundongos , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Animais , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/metabolismo , Movimento Celular , Prognóstico , Linhagem Celular Tumoral , Processamento Alternativo , Feminino , Glutamina/metabolismo , Masculino
3.
Small ; : e2402072, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773874

RESUMO

Prussian blue analogues (PBAs) exhibiting hollow morphologies have garnered considerable attention owing to their remarkable electrochemical properties. In this study, a one-pot strategy is proposed for the synthesis of MnFe PBA open cages. The materials are subsequently employed as cathode electrode in sodium-ion batteries (SIBs). The simultaneous evolution of structure, morphology, and performance during the synthesis process is investigated. The findings reveal substantial structural modifications as the reaction time is prolonged. The manganese content in the samples diminishes considerably, while the potassium content experiences an increase. This compositional variation is accompanied by a significant change in the spin state of the transition metal ions. These structural transformations trigger the occurrence of the Kirkendall effect and Oswald ripening, culminating in a profound alteration of the morphology of MnFe PBA. Moreover, the shifts in spin states give rise to distinct changes in their charge-discharge profiles and redox potentials. Furthermore, an exploration of the formation conditions of the samples and their variations before and after cycling is conducted. This study offers valuable insights into the intricate relationship between the structure, morphology, and electrochemical performance of MnFe PBA, paving the way for further optimizations in this promising class of materials for energy storage applications.

4.
Phys Chem Chem Phys ; 26(13): 10399-10407, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38502152

RESUMO

Pressure alters the nature of chemical bonds and triggers novel reactions. Here, we employed first-principles calculations combined with the CALYPSO structural search technique to reveal the charge transfer reversal between Ca and Te under high pressure in the calcium-tellurium compound (CaxTe1-x, x = 1/4, 1/3, 1/2, 2/3). We predict several new phases with conventional and unconventional compounds and found an unfamiliar phenomenon: the Ca-Te compounds will reverse charge transfer between Ca and Te atoms and decompose into elemental solids under pressure. The Bader charge analyses indicate that the Ca2+ ion gains electrons and becomes an anion under high pressure. This leads to a weakened electrostatic interaction between Ca and Te and ultimately results in decomposition. The calculated band occupation number suggests that the occupation of Ca 3d orbitals under high pressure corresponds to this atypical phenomenon. Our results demonstrated the reverse charge transfer between Ca and Te and, in addition, clarified the mechanism of CaxTe1-x decomposition into solid Ca and Te elements under high pressure, providing important insights into the evolution of the properties of alkaline-earth chalcogenide compounds under high pressure.

5.
Cancer Sci ; 114(12): 4607-4621, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37770420

RESUMO

Evaluating the accuracy of pulmonary nodule diagnosis avoids repeated low-dose computed tomography (LDCT)/CT scans or invasive examination, yet remains a main clinical challenge. Screening for new diagnostic tools is urgent. Herein, we established a nomogram based on the diagnostic signature of five circulating tsRNAs and CT information to predict malignant pulmonary nodules. In total, 249 blood samples of patients with pulmonary nodules were selected from three different lung cancer centers. Five tsRNAs were identified in the discovery and training cohorts and the diagnostic signature was established by the randomForest algorithm (tRF-Ser-TGA-003, tRF-Val-CAC-005, tRF-Ala-AGC-060, tRF-Val-CAC-024, and tiRNA-Gln-TTG-001). A nomogram was developed by combining tsRNA signature and CT information. The high level of accuracy was identified in an internal validation cohort (n = 83, area under the receiver operating characteristic curve [AUC] = 0.930, sensitivity 100.0%, specificity 73.8%) and external validation cohort (n = 66, AUC = 0.943, sensitivity 100.0%, specificity 86.8%). Furthermore, the diagnostic ability of our model discriminating invasive malignant ones from noninvasive lesions was assessed. A robust performance was achieved in the diagnosis of invasive malignant lesions in both training and validation cohorts (discovery cohort: AUC = 0.850, sensitivity 86.0%, specificity 81.4%; internal validation cohort: AUC = 0.784, sensitivity 78.8%, specificity 78.1%; and external validation cohort: AUC = 0.837, sensitivity 85.7%, specificity 84.0%). This novel circulating tsRNA-based diagnostic model has potential significance in predicting malignant pulmonary nodules. Application of the model could improve the accuracy of pulmonary nodule diagnosis and optimize surgical plans.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Humanos , Nomogramas , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Tomografia Computadorizada por Raios X/métodos , Pulmão/patologia , Estudos Retrospectivos
6.
BMC Cancer ; 23(1): 282, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36978035

RESUMO

BACKGROUND: Acapella plus active cycle of breathing technique (ACBT), external diaphragm pacemaker (EDP) plus ACBT have been shown to facilitate the recovery of functional capacity and lung function in patients suffering from airway obstruction but the efficacy in perioperative patients with lung cancer has not been proven. METHODS: We conducted a three-arm, prospective, randomized, assessor-blinded, controlled trial in patients with lung cancer who underwent thoracoscopic lobectomy or segmentectomy in the department of thoracic surgery, China. Patients were randomly assigned (1:1:1) to receive Acapella plus ACBT, EDP plus ACBT, or ACBT group (control group) using SAS software. The primary outcome was functional capacity, measured by the 6-minute walk test (6MWT). RESULTS: We recruited 363 participants over 17 months: 123 assigned to the Acapella plus ACBT group, 119 to the EDP plus ACBT group, and 121 to the ACBT group. Statistically significant differences were noted for functional capacity between the EDP plus ACBT and control groups at each follow-up time (1-week follow-up: difference = 47.25 m, 95% CI, 31.56-62.93; P < 0.001; and 1-month follow-up: difference = 49.72 m, 95% CI, 34.04-65.41; P < 0.001), between the Acapella plus ACBT and control groups at postoperative week 1 (difference = 35.23 m, 95% CI, 19.30-51.16; P < 0.001) and postoperative month 1 (difference = 34.96 m, 95% CI, 19.03-50.89; P < 0.001), and between the EDP plus ACBT and Acapella plus ACBT groups at 1-month follow-up (difference = 14.76 m, 95% CI, 1.34-28.19; P = 0.0316). CONCLUSION: EDP plus ACBT and Acapella plus ACBT significantly improved functional capacity and lung function in perioperative patients with lung cancer, compared with single-model ACBT, and the effects of EDP plus ACBT were clearly superior to those of other programs. TRIAL REGISTRATION: The study was registered in the clinical trial database (clinicaltrials.gov) on June 4, 2021 (No. NCT04914624).


Assuntos
Diafragma , Neoplasias Pulmonares , Humanos , Diafragma/cirurgia , Estudos Prospectivos , Terapia Respiratória/métodos , Neoplasias Pulmonares/cirurgia , Modalidades de Fisioterapia
7.
Phys Chem Chem Phys ; 25(10): 7366-7372, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36825775

RESUMO

The magnetic properties and electrical transport behaviors of half-metallic ferromagnet chromium dioxide (CrO2) powders under high pressure have been investigated by in situ electrical resistivity, magneto-resistivity, and Hall-effect measurements. Our results reveal that the Hall coefficient, carrier concentration, and mobility all present discontinuous changes from 11.7 GPa to 14.9 GPa which can be attributed to the second-order structural transition from the rutile-type to CaCl2-type. However, the resistivity decreases monotonically from ambient pressure to 16.5 GPa. This is due to, first, the decreased carrier concentration and the increased carrier mobility canceling the effects of each other on the resistivity; second, according to the calculation results, the bandgap of CrO2 decreased gradually with the pressure, and the bandgaps of the rutile-type phase and the CaCl2-type phase are extremely similar. CrO2 exhibits a linear and negative magnetoresistance under the applied magnetic field (0∼ ± 15 kOe). As the pressure increases, the magnetoresistance remains negative, but it becomes nonlinear and less symmetric, suggesting that pressure has an appreciable impact on the double-exchange mechanism leading to ferromagnetism in CrO2.

8.
Phys Chem Chem Phys ; 25(35): 23448-23453, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37602403

RESUMO

This work utilized first-principles calculations and the CALYPSO structure search technique to systematically investigate the crystal structure stability of CsxIy compounds under high pressures ranging from 0 to 500 GPa. Several new phases with both conventional and unconventional stoichiometries were predicted. Interestingly, we discovered a counter-intuitive phenomenon where Cs-I compounds decompose into Cs and I elemental solids under pressure. To understand the physical mechanism behind this pressure-induced decomposition, we examine the phenomenon from two distinct perspectives: enthalpy of formation and interatomic interactions. Our results suggest that the main cause is the weakening of electrostatic interactions leading to the decomposition, while the weak covalent interaction plays a minor role. From an energy perspective, the decrease in the formation of enthalpy (ΔH) is primarily due to a reduction in the difference of internal energy (ΔU). These findings provide valuable insights into the decomposition mechanism and high-pressure properties of alkali metal halides. The counterintuitive phenomenon of high-pressure charge transfer and decomposition may inspire new ideas and perspectives in the fields of geology and the study of alkali metal halides under extreme conditions.

9.
Biotechnol Lett ; 45(11-12): 1431-1440, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37736778

RESUMO

OBJECTIVES: Human heart-type fatty acid binding protein (HFABP) is a biomarker for diagnosis, risk assessment, and prognosis of acute myocardial infarction, and we aimed to establish an immunoassay for HFABP quantitation. METHODS: Human HFABP monoclonal antibodies (mAbs) were developed, evaluated by enzyme-linked immunosorbent assay, and a chemiluminescence enzyme immunoassay (CLEIA) generated. Analytical performance of the CLEIA was evaluated by measuring serum HFABP. RESULTS: The prokaryotically expressed rHFABP was purified and four anti-HFABP mAbs with superior detection performance were obtained after immunizing BALB/c mice. MAbs 2B8 and 6B3 were selected as respective capture and detection antibodies for HFABP measurement by CLEIA (detection range, 0.01-128 µg/L). Results using the CLEIA showed excellent correlation (r, 0.9622) and the correlation coefficient was 0.9809 (P < 0.05) by the Tukey test statistical analysis with those of latex-enhanced immunoturbidimetry in hospitals. CONCLUSION: Our mAbs and CLEIA for HFABP detection represent new diagnostic tools for measurement of human serum HFABP.


Assuntos
Anticorpos Monoclonais , Luminescência , Animais , Camundongos , Humanos , Ensaio de Imunoadsorção Enzimática/métodos , Imunoensaio/métodos , Biomarcadores
10.
Molecules ; 28(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37241802

RESUMO

Nanodiamonds (NDs) are emerging as a promising candidate for multimodal bioimaging on account of their optical and spectroscopic properties. NDs are extensively utilized for bioimaging probes due to their defects and admixtures in their crystal lattice. There are many optically active defects presented in NDs called color centers, which are highly photostable, extremely sensitive to bioimaging, and capable of electron leap in the forbidden band; further, they absorb or emit light when leaping, enabling the nanodiamond to fluoresce. Fluorescent imaging plays a significant role in bioscience research, but traditional fluorescent dyes have some drawbacks in physical, optical and toxicity aspects. As a novel fluorescent labeling tool, NDs have become the focus of research in the field of biomarkers in recent years because of their various irreplaceable advantages. This review primarily focuses on the recent application progress of nanodiamonds in the field of bioimaging. In this paper, we will summarize the progress of ND research from the following aspects (including fluorescence imaging, Raman imaging, X-ray imaging, magnetic modulation fluorescence imaging, magnetic resonance imaging, cathodoluminescence imaging, and optical coherence tomography imaging) and expect to supply an outlook contribution for future nanodiamond exploration in bioimaging.


Assuntos
Nanodiamantes , Nanodiamantes/química , Imagem Óptica/métodos , Corantes Fluorescentes/química , Tomografia de Coerência Óptica
11.
Molecules ; 28(3)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36771000

RESUMO

Diamond holds promise for optoelectronic devices working in high-frequency, high-power and high-temperature environments, for example in some aspect of nuclear energetics industry processing and aerospace due to its wide bandgap (5.5 eV), ultimate thermal conductivity, high-pressure resistance, high radio frequency and high chemical stability. In the last several years, p-type B-doped diamond (BDD) has been fabricated to heterojunctions with all kinds of non-metal oxide (AlN, GaN, Si and carbon-based semiconductors) to form heterojunctions, which may be widely utilized in various optoelectronic device technology. This article discusses the application of diamond-based heterostructures and mainly writes about optoelectronic device fabrication, optoelectronic performance research, LEDs, photodetectors, and high-electron mobility transistor (HEMT) device applications based on diamond non-metal oxide (AlN, GaN, Si and carbon-based semiconductor) heterojunction. The discussion in this paper will provide a new scheme for the improvement of high-temperature diamond-based optoelectronics.

12.
Opt Express ; 30(7): 11604-11618, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35473101

RESUMO

A random coding method for a Brillouin optical time domain reflectometer (BOTDR) fiber sensor is proposed. In this method, a series of pulses modulated by random code are injected into the optical fiber to enhance the signal-to-noise ratio (SNR) and further improve the measurement accuracy. Random coding method allows the sensing range to be extended to several tens of kilometers while maintaining meter-scale spatial resolution and lower detection peak power, without modifying the conventional configuration of BOTDR. The decoding principle and the coding gain of random coding method are analyzed and simulated. We experimentally implement the method and evaluate its influence on the performance optimization of BOTDR. Compared with the single pulse with peak power of 10 mW, the measured BFS uncertainty over 4.93 km sensing fiber is reduced from 5.34 MHz to 0.38 MHz when 512-bit random coding pulses with the same peak power are utilized. The experimental results show that the coding gain of 11.93 dB is obtained by 512-bit random coding. Benefitting from the SNR enhancement, the sensing range is extended from 4.93 km to 64.76 km within a root-mean-square error (RMSE) of 3 MHz, when the pulse peak power is only 10 mW and the spatial resolution is 2 m.

13.
Opt Express ; 30(14): 25865-25875, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-36237107

RESUMO

The organic semiconductor lasers (OSLs) have been seen as a promising light source for future applications. Achieving organic semiconductors with low amplified spontaneous emission (ASE) threshold is a key progress toward the electrically pumped OSLs. In this paper, the ASE properties of CBP: 2wt% BUBD-1 blend films were optimized using buffer layers containing silver nanoparticles (Ag NPs) with different ratios. Both photoluminescence intensity and ASE properties of blend films were optimized when the buffer layer with 25 vol% Ag NPs was introduced. The lowest ASE threshold is 0.47 µJ/Pulse (6.71 µJ/cm2), which reduces 67.6%, and the highest gain factor is 20.14 cm-1, which enhances 47.8% compared with that without buffer layers. The enhancement of ASE properties of blend films was ascribed to the four functions of the Ag NPs doped buffer layers, including the low refractive index of PMMA and the triple localized surface plasmon resonance (LSPR) effects of Ag NPs in buffer layers. The results show that the buffer layer modified by metal nanoparticles has great application potential in improving the lasing performance of organic small molecules.

14.
Pharm Res ; 39(10): 2459-2474, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36171345

RESUMO

PURPOSE: The purpose of the present study was to explore the feasibility of transdermal delivery of metformin, a commonly used oral antidiabetic drug, by ionic liquid (IL) technology. METHODS: Metformin hydrochloride (MetHCl) was first transformed into three kinds of ILs with different counterions. The physicochemical properties of the obtained ILs were characterized in depth. The simulation of stable configuration and calculation of interaction energies were conducted based on density functional theory (DFT). Skin-PAMPA was used to evaluate the intrinsic transdermal permeation properties. The cytotoxicity assay of these ILs was conducted using HaCaT cells to evaluate the toxicity to skin. These metformin ILs were then formulated into transdermal patch, and the transdermal potential was further evaluated using in vitro dissolution test and skin permeation assay. Finally, the pharmacokinetic profiles of these metformin IL-containing patches were determined. RESULTS: Among all the three Met ILs, metformin dihexyl sulfosuccinate (MetDH) with proper overall physiochemical and biological properties demonstrated the highest relative bioavailability. Metformin docusate (MetD) with the highest lipophilicity and intrinsic transdermal permeability exhibited the most significant sustained release profile in vivo. Both MetDH and MetD were the promising candidates for further clinical investigations. CONCLUSIONS: Overall, the properties of ILs were closely related to the structures of counterion. IL technology provided the opportunities to finely tune the solid-state and biological properties of Metformin and facilitated the successful delivery by transdermal route.


Assuntos
Líquidos Iônicos , Metformina , Administração Cutânea , Preparações de Ação Retardada , Ácido Dioctil Sulfossuccínico/metabolismo , Hipoglicemiantes/metabolismo , Líquidos Iônicos/química , Líquidos Iônicos/metabolismo , Pele/metabolismo , Absorção Cutânea , Adesivo Transdérmico
15.
Bioorg Med Chem ; 73: 117006, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36150342

RESUMO

Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) is an important virulence factor that blocks the host immune response and facilitates M. tuberculosis growth in host cells. MptpB inhibitors are potential components of tuberculosis combination treatment. Herein, we present the development of new biphenyls MptpB inhibitors with greatly improved MptpB inhibition based on our reported thiobarbiturate lead 6 by rational design with the structure-based strategy. The eight biphenyls bearing thiobarbiturate fragment target compounds showed more potent MptpB inhibition (IC50: 1.18-14.13 µM) than the lead compound 6. Further molecular docking studies showed that compounds 13, 26, 27 and 28 had multiple interactions with active sites. Among them, compound 13 exhibited dose-dependent increased antituberculosis activity in mouse macrophages. The results displayed that the strategy of modification utilizing biphenyl scaffold was efficient. Our study identifies biphenyls bearing thiobarbiturate fragment as new MptpB inhibitors and verifies the therapeutic potential of antimycobacterial agent targeting MptpB.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Animais , Antituberculosos/química , Proteínas de Bactérias/metabolismo , Compostos de Bifenilo , Inibidores Enzimáticos/química , Camundongos , Simulação de Acoplamento Molecular , Mycobacterium tuberculosis/metabolismo , Proteínas Tirosina Fosfatases , Tiobarbitúricos , Tuberculose/microbiologia , Fatores de Virulência
16.
Bioorg Med Chem ; 75: 117071, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36332597

RESUMO

ALK is an attractive therapeutic target for the treatment of non-small cell lung cancer. As an emerging element in medicinal chemistry, boron has achieved great success in the discovery of antitumor drugs and antibacterial agents. Through construction of a BCC (boron-containing compound) compound library and broad kinase screening, we found the ALK inhibitor hit compound 10a. Structural optimization by CADD and isosterism revealed that lead compound 10k has improved activity (ALKL1196M IC50 = 8.4 nM, NCI-H2228 cells IC50 = 520 nM) and better in vitro metabolic stability (human liver microsomes, T1/2 = 238 min). Compound 10k showed good in vivo efficacy in a nude mouse NCI-H2228 lung cancer xenograft model with a TGI of 52 %. Molecular simulation analysis results show that the hydroxyl group on the oxaborole forms a key hydrogen bond with Asn1254 or Asp1270, and this binding site provides a new idea for drug design. This is the first publicly reported lead compound for a boron-containing ALK inhibitor.

17.
Biotechnol Lett ; 44(5-6): 777-786, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35416565

RESUMO

Legionella pneumophila is the major causative agent of Legionnaires' disease and Pontiac fever, which pose major public health problems. Rapid detection of L. pneumophila is important for global control of these diseases. Aptamers, short oligonucleotides that bind to targets with high affinity and specificity, have great potential for use in pathogenic bacterium detection, diagnostics, and therapy. Here, we used a whole-cell SELEX (systematic evolution of ligands by exponential enrichment) method to isolate and characterize single-stranded DNA (ssDNA) aptamers against L. pneumophila. A total of 60 ssDNA sequences were identified after 17 rounds of selection. Other bacterial species (Escherichia coli, Bacillus subtilis, Pseudomonas syringae, Staphylococcus aureus, Legionella quateirensis, and Legionella adelaidensis) were used for counterselection to enhance the specificity of ssDNA aptamers against L. pneumophila. Four ssDNA aptamers showed strong affinity and high selectivity for L. pneumophila, with Kd values in the nanomolar range. Bioinformatic analysis of the most specific aptamers revealed predicted conserved secondary structures that might bind to L. pneumophila cell walls. In addition, the binding of these four fluorescently labeled aptamers to the surface of L. pneumophila was observed directly by fluorescence microscopy. These aptamers identified in this study could be used in the future to develop medical diagnostic tools and public environmental detection assays for L. pneumophila.


Assuntos
Aptâmeros de Nucleotídeos , Legionella pneumophila , Aptâmeros de Nucleotídeos/química , DNA de Cadeia Simples/genética , Escherichia coli/genética , Legionella pneumophila/genética , Legionella pneumophila/metabolismo , Técnica de Seleção de Aptâmeros
18.
Hereditas ; 159(1): 21, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35549778

RESUMO

BACKGROUND: Ferroptosis, a novel manner of cell death depended on iron ion, contributed to goat mammary epithelial cell dysfunction. Interleukin-6 (IL-6) is a major pro-inflammatory factor during many inflammation-related diseases including mastitis, and a quite recently identified ferroptosis inducer. This study aims to explore the role of IL-6 in the dysfunction of goat mammary epithelial cells (GMECs) and how the level of IL-6 was regulated. METHODS: Primary GMECs were isolated, cultured and treated with lipopolysaccharide (LPS) alone or together with Ferrostatin-1 (Fer-1), a well-known ferroptosis inhibitor. CCK-8 was used to detect cell viability, ELISA was used to detect TNF-α content, and the levels of ROS, GSH and MDA were analyzed with DCFDA-cell ROS detection kit, GSH assay kit and MDA assay kit, respectively. The iron ion level was measured with an iron assay kit. RESULTS: The expression level of IL-6 protein in GMECs was up-regulated in response to LPS treatment, and the secretion of TNF-α, the cell oxidative stress level and the Fe2+ ion content was robustly increased, which could be reversed by Fer-1 treatment. Knockdown of IL-6 decreased cell oxidative stress level and inhibited ferroptosis in LPS-treated GMECs. Further, ubiquitin experiment and co-immunoprecipitation assay showed that USP14 upregulated IL-6 protein expression by reducing the ubiquitination of IL-6, and overexpression of IL-6 reversed the inhibitory effect of USP14 shRNA on LPS-treated GMECs ferroptosis. The NRF2 inhibitor Brusatol reversed the inhibitory effect of IL-6 shRNA on LPS-treated ferroptosis. CONCLUSION: IL-6 protein is deubiquitinated by USP14 and upregulated in LPS-treated GMECs, further promoting ferroptosis and inflammation through the NRF2 signaling pathway.


Assuntos
Ferroptose , Animais , Células Epiteliais/metabolismo , Feminino , Cabras/metabolismo , Inflamação/genética , Inflamação/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Ferro/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , RNA Interferente Pequeno , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
19.
Sensors (Basel) ; 22(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36080908

RESUMO

Automatic modulation classification (AMC) plays a fundamental role in common communication systems. Existing clustering models typically handle fewer modulation types with lower classification accuracies and more computational resources. This paper proposes a hierarchical self-organizing map (SOM) based on a feature space composed of high-order cumulants (HOC) and amplitude moment features. This SOM with two stacked layers can identify intrinsic differences among samples in the feature space without the need to set thresholds. This model can roughly cluster the multiple amplitude-shift keying (MASK), multiple phase-shift keying (MPSK), and multiple quadrature amplitude keying (MQAM) samples in the root layer and then finely distinguish the samples with different orders in the leaf layers. We creatively implement a discrete transformation method based on modified activation functions. This method causes MQAM samples to cluster in the leaf layer with more distinct boundaries between clusters and higher classification accuracies. The simulation results demonstrate the superior performance of the proposed hierarchical SOM on AMC problems when compared with other clustering models. Our proposed method can manage more categories of modulation signals and obtain higher classification accuracies while using fewer computational resources.


Assuntos
Algoritmos , Análise por Conglomerados , Simulação por Computador
20.
Int J Mol Sci ; 23(7)2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35409191

RESUMO

The hydrothermal approach has been used to fabricate a heterojunction of n-aluminum-doped ZnO nanorods/p-B-doped diamond (n-Al:ZnO NRs/p-BDD). It exhibits a significant increase in photoluminescence (PL) intensity and a blue shift of the UV emission peak when compared to the n-ZnO NRs/p-BDD heterojunction. The current voltage (I-V) characteristics exhibit excellent rectifying behavior with a high rectification ratio of 838 at 5 V. The n-Al:ZnO NRs/p-BDD heterojunction shows a minimum turn-on voltage (0.27 V) and reverse leakage current (0.077 µA). The forward current of the n-Al:ZnO NRs/p-BDD heterojunction is more than 1300 times than that of the n-ZnO NRs/p-BDD heterojunction at 5 V. The ideality factor and the barrier height of the Al-doped device were found to decrease. The electrical transport behavior and carrier injection process of the n-Al:ZnO NRs/p-BDD heterojunction were analyzed through the equilibrium energy band diagrams and semiconductor theoretical models.


Assuntos
Nanotubos , Óxido de Zinco , Diamante , Semicondutores
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