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1.
ACS Omega ; 7(35): 31482-31494, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36092633

RESUMO

Artesunate is a widely used drug in clinical treatment of malaria. The aim of this study was to investigate the therapeutic mechanism of artesunate on malaria using an integrated strategy of network pharmacology and serum metabolomics. The mice models of malaria were established using 2 × 107 red blood cells infected with Plasmodium berghei ANKA injection. Giemsa and hematoxylin-eosin (HE) staining were used to evaluate the efficacy of artesunate on malaria. Next, network pharmacology analysis was applied to identify target genes. Then, a metabolomics strategy has been developed to find the possible significant serum metabolites and metabolic pathways induced by artesunate. Additionally, two parts of the results were integrated to confirm each other. Giemsa and HE staining results showed that artesunate significantly inhibited the proliferation of Plasmodium and reduced liver and spleen inflammation. Based on metabolomics, 18 differential endogenous metabolites were identified as potential biomarkers related to the artesunate for treating malaria. These metabolites were mainly involved in the relevant pathways of biosynthesis of unsaturated fatty acids; aminoacyl-tRNA biosynthesis; valine, leucine, and isoleucine biosynthesis; and phenylalanine, tyrosine, and tryptophan biosynthesis. The results of the network pharmacology analysis showed 125 potential target genes related to the treatment of malaria with artesunate. The functional enrichment was mainly associated with lipid and atherosclerosis; pathways of prostate cancer and proteoglycans in cancer; and PI3K-Akt, apoptosis, NF-κB, Th17 cell, and AGE-RAGE signaling pathways. These findings were partly consistent with the findings of the metabolism. Our results further suggested that artesunate could correct the inflammatory response caused by malaria through Th17 cell and NF-κB pathways. Meanwhile, our work revealed that cholesterol needed by Plasmodium berghei came directly from serum. Cholesterol and palmitic acid may be essential in the growth and reproduction of Plasmodium berghei. In summary, artesunate may have an effect on anti-malarial properties through multiple targets.

2.
Biomacromolecules ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36094894

RESUMO

As a biodegradable elastomer, poly(1,8-octanediol-co-citrate) (POC) has been widely applied in tissue engineering and implantable electronics. However, the unclear degradation mechanism has posed a great challenge for the better application and development of POC. To reveal the degradation mechanism, here, we present a systematic investigation into in vivo and in vitro degradation behaviors of POC. Initially, critical factors, including chemical structures, hydrophilic and water-absorbency characteristics, and degradation reaction of POC, are investigated. Then, various degradation-induced changes during in vitro degradation of POC-x (POC with different cross-linking densities) are monitored and discussed. The results show that (1) cross-linking densities exponentially drop with degradation time; (2) mass loss and PBS-absorption ratio grow nonlinearly; (3) the morphology on the cross-section changes from flat to rough at a microscopic level; (4) the cubic samples keep swelling until they collapse into fragments from a macro view; and (5) the mechanical properties experience a sharp drop at the beginning of degradation. Finally, the in vivo degradation behaviors of POC-x are investigated, and the results are similar to those in vitro. The comprehensive assessment suggests that the in vitro and in vivo degradation of POC occurs primarily through bulk erosion. Inflammation responses triggered by the degradation of POC-x are comparable to poly(lactic acid), or even less obvious. In addition, the mechanical evaluation of POC in the simulated application environment is first proposed and conducted in this work for a more appropriate application. The degradation mechanism of POC revealed will greatly promote the further development and application of POC-based materials in the biomedical field.

3.
Infect Immun ; 90(9): e0023922, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35938858

RESUMO

Nitrate metabolism is an adaptation mechanism used by many bacteria for survival in anaerobic environments. As a by-product of inflammation, nitrate is used by the intestinal bacterial pathogens to enable gut infection. However, the responses of bacterial respiratory pathogens to nitrate are less well understood. Actinobacillus pleuropneumoniae is an important bacterial respiratory pathogen of swine. Previous studies have suggested that adaptation of A. pleuropneumoniae to anaerobiosis is important for infection. In this work, A. pleuropneumoniae growth and pathogenesis in response to the nitrate were investigated. Nitrate significantly promoted A. pleuropneumoniae growth under anaerobic conditions in vitro and lethality in mice. By using narQ and narP deletion mutants and single-residue-mutated complementary strains of ΔnarQ, the two-component system NarQ/P was confirmed to be critical for nitrate-induced growth, with Arg50 in NarQ as an essential functional residue. Transcriptome analysis showed that nitrate upregulated multiple energy-generating pathways, including nitrate metabolism, mannose and pentose metabolism, and glycerolipid metabolism via the regulation of NarQ/P. Furthermore, narQ, narP, and its target gene encoding the nitrate reductase Nap contributed to the pathogenicity of A. pleuropneumoniae. The Nap inhibitor tungstate significantly reduced the survival of A. pleuropneumoniae in vivo, suggesting that Nap is a potential drug target. These results give new insights into how the respiratory pathogen A. pleuropneumoniae utilizes the alternative electron acceptor nitrate to overcome the hypoxia microenvironment, which can occur in the inflammatory or necrotic infected tissues.


Assuntos
Infecções por Actinobacillus , Actinobacillus pleuropneumoniae , Actinobacillus pleuropneumoniae/genética , Actinobacillus pleuropneumoniae/metabolismo , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Manose/metabolismo , Camundongos , Nitrato Redutases/genética , Nitrato Redutases/metabolismo , Nitratos/metabolismo , Pentoses/metabolismo , Suínos , Virulência
4.
Dalton Trans ; 51(29): 10965-10972, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35775649

RESUMO

Cr3+-Activated broadband near-infrared (NIR) luminescence materials are attracting much attention as next-generation smart NIR light sources that are widely used in night vision, bioimaging, medical treatment, and many other fields. Herein, a series of Na3GaxAl1-xF6:Cr3+ NIR phosphors with broadband emission and tunable luminescence properties were designed and prepared. The luminescence intensity, peak position and full width at half maximum (FWHM) of the materials can be controlled by adjusting the crystal field strength. Furthermore, Na3Ga0.75Al0.25F6:0.35Cr3+ exhibited high luminous efficiency and the emission intensity remained 81% at 423 K compared with the initial value at 298 K. The structural confinement and the electron-phonon coupling (EPC) effect may account for its good thermal stability. Finally, a pc-NIR-LED device with a photoelectric conversion efficiency of 6.53% at 350 mA was fabricated by combining the as-prepared NIR phosphor and a blue InGaN chip, and its applications in night vision and medical fields were further investigated. This work will promote the development of NIR phosphors with tunable luminescence properties.


Assuntos
Luminescência , Sódio , Íons
5.
Front Med (Lausanne) ; 9: 842428, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35721060

RESUMO

Background: To investigate the influence of HbA1c level and GWG on pregnancy outcomes in pregnant women with GDM. Methods: A total of 2,171 pregnant women with GDM were retrospectively included and categorized as follows: (1) normal (HbA1c <6%) and elevated (HbA1c ≥6%) HbA1c groups according to the HbA1c level in the second trimester, and (2) inadequate, appropriate, and excessive GWG groups according to the IOM guidelines. Results: In pregnant women with GDM, advanced age and high pre-pregnancy BMI were high-risk factors for elevated HbA1c. Pregnant women with elevated HbA1c had higher OGTT levels than those with normal HbA1c, and the risks of adverse pregnancy outcomes were higher (P < 0.05). The risks of primary cesarean section, hypertensive disorders during pregnancy, and macrosomia in pregnant women with excessive GWG were significantly higher than those with inadequate and appropriate GWG (P < 0.05). When GWG was appropriate, the risk of hypertensive disorders during pregnancy in the elevated HbA1c group was higher than that in the normal HbA1c group. When GWG was excessive, the risks of postpartum hemorrhage, macrosomia, and neonatal asphyxia in the elevated HbA1c group were significantly higher than in the normal HbA1c group (P < 0.05). Conclusion: Monitoring and controlling blood glucose levels have shown effectiveness in reducing the adverse pregnancy outcomes in women with GDM, particularly for those who had excessive GWG.

6.
J Immunol ; 208(12): 2795-2805, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35688466

RESUMO

Defensins are a major class of antimicrobial peptides that facilitate the immune system to resist pathogen infection. To date, only ß-defensins have been identified in pigs. In our previous studies, porcine ß-defensin 2 (PBD-2) was shown to have both bactericidal activity and modulatory roles on inflammation. PBD-2 can interact with the cell surface TLR4 and interfere with the NF-κB signaling pathway to suppress the inflammatory response. In this study, the intracellular functions of PBD-2 were investigated. The fluorescently labeled PBD-2 could actively enter mouse macrophage cells. Proteomic analysis indicated that 37 proteins potentially interacted with PBD-2, among which vasohibin-1 (VASH1) was further tested. LPS, an inflammation inducer, suppressed the expression of VASH1, whereas PBD-2 inhibited this effect. PBD-2 inhibited LPS-induced activation of Akt, expression and release of the inflammatory mediators vascular endothelial growth factor and NO, and cell damage. A follow-up VASH1 knockdown assay validated the specificity of the above observations. In addition, PBD-2 inhibited LPS-induced NF-κB activation via Akt. The inhibition effects of PBD-2 on LPS triggered suppression of VASH1 and activation of Akt, and NF-κB and inflammatory cytokines were also confirmed using pig alveolar macrophage 3D4/21 cells. Therefore, the data indicate that PBD-2 interacts with intracellular VASH1, which inhibits the LPS-induced Akt/NF-κB signaling pathway, resulting in suppression of inflammatory responses. Together with our previous findings, we conclude that PBD-2 interacts with both the cell surface receptor (TLR4) and also with the intracellular receptor (VASH1) to control inflammation, thereby providing insights into the immunomodulatory roles of defensins.


Assuntos
Proteínas de Ciclo Celular/metabolismo , NF-kappa B , beta-Defensinas , Animais , Inflamação , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B/metabolismo , Proteômica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Suínos , Receptor 4 Toll-Like , Fator A de Crescimento do Endotélio Vascular/farmacologia , beta-Defensinas/farmacologia
7.
Dalton Trans ; 51(24): 9501-9510, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35687324

RESUMO

Developing novel luminescent materials with ideal properties is an endless project, urged by growing requirements of advances in energy saving, healthy lighting and environmental friendliness. Herein, a series of ScCaOBO3:Ce3+,Mn2+ phosphors with excellent luminescence properties were synthesized by the high temperature solid state method. X-ray diffraction was applied to analyse the phase composition of the obtained phosphors. The morphology and dopant distribution were observed by scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS), respectively. The Rietveld refinements and luminescence spectra indicate that Ce3+ preferentially occupies the Sc3+ site and produces a blue emission band at around 460 nm, which originates from the characteristic 5d-4f transitions, while Mn2+ preferentially occupies the Ca2+ site and emits red light due to its characteristic 4T1(4G)-6A1(6S) transitions. Upon excitation at 354 nm, both Ce3+ and Mn2+ emissions can be obtained and further investigations evidenced that the broad and intense light emission of Mn2+ located in the red spectral region is the result of energy transfer from Ce3+ to Mn2+. Theoretical calculations reveal that the energy transfer process from Ce3+ to Mn2+ is of the resonance type and is governed by electric dipole-dipole interactions. Since the ScCaOBO3:Ce3+,Mn2+ phosphors are capable of producing broadband emissions that widely cover the blue and red spectral regions, the introduction of a green light-emitting phosphor CMA:Tb3+ can conveniently generate high quality white light. Therefore, a white light-emitting diode device with extremely high color rendering indices, Ra = 93.7 and R9 = 91.9, was successfully obtained.


Assuntos
Luminescência , Manganês , Transferência de Energia , Manganês/química , Raios Ultravioleta , Difração de Raios X
8.
Small ; 18(19): e2200533, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35388964

RESUMO

The demand for stretchable electronics with a broader working range is increasing for wide application in wearable sensors and e-skin. However, stretchable conductors based on soft elastomers always exhibit low working range due to the inhomogeneous breakage of the conductive network when stretched. Here, a highly stretchable and self-healable conductor is reported by adopting polyrotaxane and disulfide bonds into the binding layer. The binding layer (PR-SS) builds the bridge between polymer substrates (PU-SS) and silver nanowires (AgNWs). The incorporation of sliding molecules endows the stretchable conductor with a long sensing range (190%) due to the energy dissipation derived from the sliding nature of polyrotaxanes, which is two times higher than the working range (93%) of conductors based on AP-SS without polyrotaxanes. Furthermore, the mechanism of sliding effect for the polyrotaxanes in the elastomers is investigated by SEM for morphological change of AgNWs, in situ small-angle x-ray scattering, as well as stress relaxation experiments. Finally, human-body-related sensing tests and a self-correction system in fitness are designed and demonstrated.


Assuntos
Ciclodextrinas , Rotaxanos , Elastômeros/química , Condutividade Elétrica , Humanos , Polímeros/química
9.
J Bacteriol ; 204(2): e0032621, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34807725

RESUMO

Bacteria have evolved a variety of enzymes to eliminate endogenous or host-derived oxidative stress factors. The Dps protein, first identified in Escherichia coli, contains a ferroxidase center, and protects bacteria from reactive oxygen species damage. Little is known of the role of Dps-like proteins in bacterial pathogenesis. Actinobacillus pleuropneumoniae causes pleuropneumonia, a respiratory disease of swine. The A. pleuropneumoniae ftpA gene is upregulated during shifts to anaerobiosis, in biofilms and, as found in this study, in the presence of H2O2. An A. pleuropneumoniae ftpA deletion mutant (ΔftpA) had increased H2O2 sensitivity, decreased intracellular viability in macrophages, and decreased virulence in a mouse infection model. Expression of ftpA in an E. coli dps mutant restored wild-type H2O2 resistance. FtpA possesses a conserved ferritin domain containing a ferroxidase site. Recombinant rFtpA bound and oxidized Fe2+ reversibly. Under aerobic conditions, the viability of an ΔftpA mutant was reduced compared with the wild-type strain after extended culture, upon transition from anaerobic to aerobic conditions, and upon supplementation with Fenton reaction substrates. Under anaerobic conditions, the addition of H2O2 resulted in a more severe growth defect of ΔftpA than it did under aerobic conditions. Therefore, by oxidizing and mineralizing Fe2+, FtpA alleviates the oxidative damage mediated by intracellular Fenton reactions. Furthermore, by mutational analysis, two residues were confirmed to be critical for Fe2+ binding and oxidization, as well as for A. pleuropneumoniae H2O2 resistance. Taken together, the results of this study demonstrate that A. pleuropneumoniae FtpA is a Dps-like protein, playing critical roles in oxidative stress resistance and virulence. IMPORTANCE As a ferroxidase, Dps of Escherichia coli can protect bacteria from reactive oxygen species damage, but its role in bacterial pathogenesis has received little attention. In this study, FtpA of the swine respiratory pathogen A. pleuropneumoniae was identified as a new Dps-like protein. It facilitated A. pleuropneumoniae resistance to H2O2, survival in macrophages, and infection in vivo. FtpA could bind and oxidize Fe2+ through two important residues in its ferroxidase site and protected the bacteria from oxidative damage mediated by the intracellular Fenton reaction. These findings provide new insights into the role of the FtpA-based antioxidant system in the pathogenesis of A. pleuropneumoniae, and the conserved Fe2+ binding ligands in Dps/FtpA provide novel drug target candidates for disease prevention.


Assuntos
Actinobacillus pleuropneumoniae/genética , Actinobacillus pleuropneumoniae/metabolismo , Proteínas de Bactérias/metabolismo , Oxirredução , Estresse Fisiológico/genética , Actinobacillus pleuropneumoniae/química , Animais , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Proteínas de Escherichia coli/genética , Feminino , Ferro/metabolismo , Camundongos , Espécies Reativas de Oxigênio , Virulência/genética
10.
Sci Adv ; 7(30)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34301608

RESUMO

A myriad of inflammatory cytokines regulate signaling pathways to maintain cellular homeostasis. The IκB kinase (IKK) complex is an integration hub for cytokines that govern nuclear factor κB (NF-κB) signaling. In response to inflammation, IKK is activated through recruitment to receptor-associated protein assemblies. How and what information IKK complexes transmit about the milieu are open questions. Here, we track dynamics of IKK complexes and nuclear NF-κB to identify upstream signaling features that determine same-cell responses. Experiments and modeling of single complexes reveal their size, number, and timing relays cytokine-specific control over shared signaling mechanisms with feedback regulation that is independent of transcription. Our results provide evidence for variable-gain stochastic pooling, a noise-reducing motif that enables cytokine-specific regulation and parsimonious information transfer. We propose that emergent properties of stochastic pooling are general principles of receptor signaling that have evolved for constructive information transmission in noisy molecular environments.

11.
Anticancer Res ; 41(6): 3023-3027, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34083293

RESUMO

BACKGROUND/AIM: Small cell cancer of the esophagus (SCCE) is an extremely rare entity with an aggressive clinical course, thus early diagnosis and treatment are important for improved survival. CASE REPORT: A 35-year-old male presented with dysphagia, loss of appetite and weight loss. Diagnostic workup revealed an esophageal mass, which was diagnosed as primary non-Hodgkin lymphoma (NHL) on initial biopsy. Despite receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy for 3 months, there was an interval increase in the size of the esophagus mass, which unveiled underlying SCCE. A re-review of the previous biopsy specimen with immunohistochemical staining confirmed the initial diagnosis as SCCE as well. Despite 4 cycles of platinum-based chemotherapy and radiotherapy, the malignancy progressed and proved fatal. CONCLUSION: SCCE and non-Hodgkin lymphomas are rare entities, whose morphologies can be diagnostically challenging, hence they require special immunostaining for accurate diagnosis. Prompt diagnosis and initiation of treatment can confer better quality of life and survival.


Assuntos
Carcinoma de Células Pequenas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Linfoma não Hodgkin/diagnóstico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/terapia , Quimiorradioterapia , Diagnóstico Diferencial , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Humanos , Masculino , Tomografia por Emissão de Pósitrons
12.
ACS Nano ; 15(5): 8001-8038, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-33900074

RESUMO

Proteins, a type of natural biopolymer that possess many prominent merits, have been widely utilized to engineer nanomedicine for fighting against cancer. Motivated by their ever-increasing attention in the scientific community, this review aims to provide a comprehensive showcase on the current landscape of protein-based nanomedicine for cancer therapy. On the basis of role differences of proteins in nanomedicine, protein-based nanomedicine engineered with protein therapeutics, protein carriers, enzymes, and composite proteins is introduced. The cancer therapeutic benefits of the protein-based nanomedicine are also discussed, including small-molecular therapeutics-mediated therapy, macromolecular therapeutics-mediated therapy, radiation-mediated therapy, reactive oxygen species-mediated therapy, and thermal effect-mediated therapy. Lastly, future developments and potential challenges of protein-based nanomedicine are elucidated toward clinical translation. It is believed that protein-based nanomedicine will play a vital role in the battle against cancer. We hope that this review will inspire extensive research interests from diverse disciplines to further push the developments of protein-based nanomedicine in the biomedical frontier, contributing to ever-greater medical advances.


Assuntos
Nanomedicina , Neoplasias , Portadores de Fármacos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico
13.
Am J Transl Res ; 13(3): 1221-1232, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841651

RESUMO

MiR-22-3p has been reported to be down-regulated in several cancers, but its expression pattern and roles in lung cancer is unclear. Given the crucial role of microRNAs in cancer progression, we examined the expression and function of miR-22-3p in lung adenocarcinoma. MiR-22-3p expression in lung cancer tissues and cell lines was measured by qRT-PCR. Cell proliferation was measured by WST-1 and colony formation assays were used to reveal the role of miR-22-3p in lung cancer in vitro. MiR-22-3p was notably down-regulated in lung cancer tissues as compared to normal lung tissues, but it was not associated with the clinical characteristics of tumor stage, differentiation and patient's smoking status. Colony formation ability and cell proliferation were suppressed by miR-22-3p mimics in lung cancer cell lines. Mechanistically, miR-22-3p mimics could reduce MET and STAT3 protein expression and induce apoptosis as measured by PARP protein. We conclude that miR-22-3p may play a tumor suppressor role via inhibiting MET-STAT3 signaling and have potential to be a therapeutic target and biomarker in lung adenocarcinoma.

14.
Nat Commun ; 12(1): 647, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510144

RESUMO

Ferroptosis is a type of iron-dependent regulated cell death, representing an emerging disease-modulatory mechanism. Transcription factors play multiple roles in ferroptosis, although the key regulator for ferroptosis in iron metabolism remains elusive. Using NanoString technology, we identify NUPR1, a stress-inducible transcription factor, as a driver of ferroptosis resistance. Mechanistically, NUPR1-mediated LCN2 expression blocks ferroptotic cell death through diminishing iron accumulation and subsequent oxidative damage. Consequently, LCN2 depletion mimics NUPR1 deficiency with respect to ferroptosis induction, whereas transfection-enforced re-expression of LCN2 restores resistance to ferroptosis in NUPR1-deficient cells. Pharmacological or genetic blockade of the NUPR1-LCN2 pathway (using NUPR1 shRNA, LCN2 shRNA, pancreas-specific Lcn2 conditional knockout mice, or the small molecule ZZW-115) increases the activity of the ferroptosis inducer erastin and worsens pancreatitis, in suitable mouse models. These findings suggest a link between NUPR1-regulated iron metabolism and ferroptosis susceptibility.


Assuntos
Proteínas de Ligação a DNA/genética , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , Ferro/metabolismo , Lipocalina-2/genética , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/genética , Animais , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Humanos , Estimativa de Kaplan-Meier , Lipocalina-2/metabolismo , Camundongos Knockout , Camundongos Nus , Camundongos Transgênicos , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Piperazinas/farmacologia , Terapêutica com RNAi/métodos , Transdução de Sinais/genética , Tiazinas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
15.
Inorg Chem ; 60(4): 2219-2227, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33507746

RESUMO

Materials with near-infrared (NIR) persistent luminescence (PersL) and NIR-to-NIR photostimulated luminescence (PSL) properties are attractive platforms for photonic energy harvesting and release. In this work, we develop Mg2SnO4:Cr as a broadband NIR PersL and NIR-to-NIR PSL material (luminescence maxima at ∼800 nm) and reveal the origin of the PersL and PSL properties. The material has an inverse spinel structure with the Mg2+ and Sn4+ disorder at the Wyckoff 16d site based on the Rietveld refinement. Cr K-edge X-ray absorption near-edge structure (XANES) spectra uncover that the doped Cr ions have a +3 valence state and occupy the disordered (Mg,Sn) site with octahedral coordination. The disorder results in multiple Cr3+ centers, and the broadband luminescence originates from the 4T2(4F) → 4A2 transition of Cr3+ at sites with intermediate crystal field strength. The distribution of trap depths is continuous according to the analysis of thermoluminescence (TL) spectra using the initial rising method, which relates to the random distribution of Mg2+ and Sn4+ at the second coordination sphere of the Cr3+ centers rather than the oxygen-related defects. Stimulating the material with a NIR laser, the NIR PersL gets significantly enhanced due to a PSL process. The broadband PersL and PSL are detectable beyond 100 h and have good tissue penetrability and therefore the developed Mg2SnO4:Cr3+ has potential in applications of optical information storage/reading and autofluorescence-free bioimaging. Finally, three crystal and electronic structure factors are proposed for screening new Cr3+-activated PersL and PSL materials.

16.
Bioinformatics ; 37(5): 677-683, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33051642

RESUMO

MOTIVATION: Many biological processes are regulated by single molecules and molecular assemblies within cells that are visible by microscopy as punctate features, often diffraction limited. Here, we present detecting-NEMO (dNEMO), a computational tool optimized for accurate and rapid measurement of fluorescent puncta in fixed-cell and time-lapse images. RESULTS: The spot detection algorithm uses the à trous wavelet transform, a computationally inexpensive method that is robust to imaging noise. By combining automated with manual spot curation in the user interface, fluorescent puncta can be carefully selected and measured against their local background to extract high-quality single-cell data. Integrated into the workflow are segmentation and spot-inspection tools that enable almost real-time interaction with images without time consuming pre-processing steps. Although the software is agnostic to the type of puncta imaged, we demonstrate dNEMO using smFISH to measure transcript numbers in single cells in addition to the transient formation of IKK/NEMO puncta from time-lapse images of cells exposed to inflammatory stimuli. We conclude that dNEMO is an ideal user interface for rapid and accurate measurement of fluorescent molecular assemblies in biological imaging data. AVAILABILITY AND IMPLEMENTATION: The data and software are freely available online at https://github.com/recleelab. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Microscopia , Software , Algoritmos , RNA Mensageiro/genética , Imagem com Lapso de Tempo
17.
Antibiotics (Basel) ; 9(12)2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33327385

RESUMO

As the causative agent of Glässer's disease, Glaesserella (Haemophilus) parasuis has led to serious economic losses to the swine industry worldwide. Due to the low cross-protection of vaccines and increasing antimicrobial resistance of G. parasuis, it is important to develop alternative approaches to prevent G. parasuis infection. Defensins are host defense peptides that have been suggested to be promising substitutes for antibiotics in animal production, while porcine ß-defensin 2 (PBD-2) is a potent antimicrobial peptide discovered in pigs. Our previous study generated transgenic (TG) pigs overexpressing PBD-2, which displayed enhanced resistance to Actinobacillus pleuropneumoniae. In this study, the antibacterial activities of PBD-2 against G. parasuis are determined in vitro and in the TG pig model. The concentration-dependent bactericidal activity of synthetic PBD-2 against G. parasuis was measured by bacterial counting. Moreover, after being infected with G. parasuis via a cohabitation challenge model, TG pigs overexpressing PBD-2 displayed significantly milder clinical signs and less severe gross pathological changes than their wild-type (WT) littermates. The TG pigs also exhibited alleviated lung and brain lesions, while bacterial loads in the lung and brain tissues of the TG pigs were significantly lower than those of the WT pigs. Additionally, lung and brain homogenates from TG pigs possessed enhanced antibacterial activity against G. parasuis when compared with those from the WT pigs. Altogether, these proved that overexpression of PBD-2 could also endow pigs with increased resilience to G. parasuis infection, which further confirmed the potential of using the PBD-2 coding gene to develop disease-resistant pigs and provided a novel strategy to combat G. parasuis as well.

18.
Adv Sci (Weinh) ; 7(7): 1902576, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32274298

RESUMO

Photothermal therapy (PTT) has emerged as a promising cancer therapeutic modality with high therapeutic specificity, however, its therapeutic effectiveness is limited by available high-efficiency photothermal agents (PTAs), especially in the second near-infrared (NIR-II) biowindow. Here, based on facile liquid-exfoliated FePS3 nanosheets, a highly efficient NIR-II PTA with its photothermal conversion efficiency of up to 43.3% is demonstrated, which is among the highest reported levels in typical PTAs. More importantly, such Fe-based 2D nanosheets also show superior Fenton catalytic activity facilitated by their ultrahigh specific surface area, simultaneously enabling cancer chemodynamic therapy (CDT). Impressively, the efficiency of CDT could be further remarkably enhanced by its photothermal effect, leading to cancer synergistic PTT/CDT. Both in vitro and in vivo studies reveal a highly efficient tumor ablation under NIR-II light irradiation. This work provides a paradigm for cancer CDT and PTT in the NIR-II biowindow via a single 2D nanoplatform with desired therapeutic effect. Furthermore, with additional possibilities for magnetic resonance imaging, photoacoustic tomography, as well as drug loading, this Fe-based 2D material could potentially serve as a 2D "all-in-one" theranostic nanoplatform.

19.
Small ; 16(8): e1906985, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32003089

RESUMO

The blood-brain barrier (BBB) is the most important obstacle to improving the clinical outcomes of diagnosis and therapy of glioblastoma. Thus, the development of a novel nanoplatform that can efficiently traverse the BBB and achieve both precise diagnosis and therapy is of great importance. Herein, an intelligent nanoplatform based on holo-transferrin (holo-Tf) with in situ growth of MnO2 nanocrystals is constructed via a reformative mild biomineralization process. Furthermore, protoporphyrin (ppIX), acting as a sonosensitizer, is then conjugated into holo-Tf to obtain MnO2 @Tf-ppIX nanoparticles (TMP). Because of the functional inheritance of holo-Tf during fabrication, TMP can effectively traverse the BBB for highly specific magnetic resonance (MR) imaging of orthotopic glioblastoma. Clear suppression of tumor growth in a C6 tumor xenograft model is achieved via sonodynamic therapy. Importantly, the experiments also indicate that the TMP nanoplatform has satisfactory biocompatibility and biosafety, which favors potential clinical translation.


Assuntos
Barreira Hematoencefálica , Glioblastoma , Imageamento por Ressonância Magnética , Nanocompostos , Terapia por Ultrassom , Animais , Barreira Hematoencefálica/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Glioblastoma/diagnóstico por imagem , Glioblastoma/terapia , Imageamento por Ressonância Magnética/métodos , Compostos de Manganês/química , Camundongos , Camundongos Nus , Óxidos/química , Terapia por Ultrassom/métodos
20.
Microbiol Res ; 230: 126343, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31539852

RESUMO

Identifying the direct target genes of response regulators (RRs) of a bacterial two-component system (TCS) is critical to understand the roles of TCS in bacterial environmental adaption and pathogenesis. Actinobacillus pleuropneumoniae is an important respiratory bacterial pathogen that causes considerable economic losses to swine industry worldwide. The targets of A. pleuropneumoniae NarP (nitrate/nitrite RR), which is the cognate RR of the nitrate/nitrite sensor histidine kinase NarQ, are still unknown. In the present study, a DNA-affinity-purified sequencing (DAP-Seq) approach was established. The upstream regions of a total of 131 candidate genes from the genome of A. pleuropneumoniae were co-purified with the activated NarP protein. Electrophoretic mobility shift assay (EMSA) results confirmed the interactions of NarP with the promoter regions of five selected target genes, including dmsA, pgaA, ftpA, cstA and ushA. The EMSA-confirmed target genes were significantly up-regulated in the narP-deleted mutant in the presence of additional nitrate, whilst the transcriptional changes were restored in the complemented strain. The NarP binding motif in the upstream regions of the target genes dmsA and ftpA were further identified and confirmed by EMSA using the truncated binding motif. The NarP binding sites were present in a total of 25.2% of the DNA fragments captured by DAP-Seq. These results demonstrated that the established DAP-Seq method is effective for exploring the direct targets of RRs of bacterial TCSs and that the A. pleuropneumoniae NarP could be a repressor in response to nitrate.


Assuntos
Actinobacillus pleuropneumoniae/genética , Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/metabolismo , Análise de Sequência de DNA/métodos , Actinobacillus pleuropneumoniae/metabolismo , Proteínas de Bactérias/genética , Proteínas de Ligação a DNA/genética , Ensaio de Desvio de Mobilidade Eletroforética , Regulação Bacteriana da Expressão Gênica , Nitratos/metabolismo , Nitritos/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Quinases/genética , Proteínas Quinases/metabolismo
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