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1.
BMC Genomics ; 25(1): 337, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38641568

RESUMO

BACKGROUND: Larval settlement and metamorphosis represent critical events in the life history of marine benthic animals. Myoinhibitory peptide (MIP) plays a pivotal role in larval settlement of marine invertebrates. However, the molecular mechanisms of MIP involved in this process are not well understood. RESULTS: In this study, we evaluated the effects of thirteen MIP mature peptides on triggering the larval settlement of Urechis unicinctus (Xenopneusta, Urechidae), and determined that MIP2 was the principal neuropeptide. Transcriptomic analysis was employed to identify differentially expressed genes (DEGs) between the MIP2-treated larvae and normal early-segmentation larvae. Both cAMP and calcium signaling pathways were enriched in the DEGs of the MIP2-treated larvae, and two neuropeptide receptor genes (Spr, Fmrfar) were up-regulated in the MIP2-treated larvae. The activation of the SPR-cAMP pathway by MIP2 was experimentally validated in HEK293T cells. Furthermore, fourteen cilia-related genes, including Tctex1d2, Cfap45, Ift43, Ift74, Ift22, Cav1 and Mns1, etc. exhibited down-regulated expression in the MIP2-treated larvae. Whole-mount in situ hybridization identified two selected ciliary genes, Tctex1d2 and Cfap45, were specially expressed in circumoral ciliary cells of the early-segmentation larvae. Knocking down Tctex1d2 mRNA levels by in vivo RNA interference significantly increased the larval settlement rate. CONCLUSION: Our findings suggest that MIP2 inhibits the function of the cilia-related genes, such as Tctex1d2, through the SPR-cAMP-PKA pathway, thereby inducing larval settlement in U. unicinctus. The study contributes important data to the understanding of neuropeptide regulation in larval settlement.


Assuntos
Neuropeptídeos , Poliquetos , Humanos , Animais , Larva/genética , Células HEK293 , Poliquetos/genética , Neuropeptídeos/genética , Neuropeptídeos/química , Perfilação da Expressão Gênica
2.
Arch Virol ; 169(4): 76, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38494576

RESUMO

The number of individuals infected with HIV-1 among men who have sex with men (MSM) has risen rapidly in recent years in China, and the subtypes CRF01_AE, CRF07_BC, and B, as well as many novel unique recombinant forms (URFs) are prevalent among them. Co-circulation of strains among MSM populations allows the generation of circulating recombinant forms (CRFs) and URFs. In this study, we identified two new URFs from two HIV-1-positive subjects who were infected through homosexual contact in Hebei, China. Analysis of near-full-length genome sequences, using phylogenetic and recombination analysis showed that the two URFs originated from CRF01_AE, CRF07_BC, and B, and CRF01_AE segments in the backbone of the URFs were derived from cluster 4 of CRF01_AE. The CRF07_BC segments of two URFs were clustered with 07BC_N in a phylogenetic tree. The identification of novel URFs with complex genomic structures shows that it is necessary to strengthen surveillance of HIV-1 variants in MSM populations in this region.


Assuntos
Infecções por HIV , HIV-1 , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Filogenia , Infecções por HIV/epidemiologia , Recombinação Genética , Análise de Sequência de DNA , Genoma Viral , China/epidemiologia , HIV-1/genética
3.
Molecules ; 29(10)2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38792257

RESUMO

Glioblastoma multiforme, a highly aggressive and lethal brain tumor, is a substantial clinical challenge and a focus of increasing concern globally. Hematological toxicity and drug resistance of first-line drugs underscore the necessity for new anti-glioma drug development. Here, 43 anthracenyl skeleton compounds as p53 activator XI-011 analogs were designed, synthesized, and evaluated for their cytotoxic effects. Five compounds (13d, 13e, 14a, 14b, and 14n) exhibited good anti-glioma activity against U87 cells, with IC50 values lower than 2 µM. Notably, 13e showed the best anti-glioma activity, with an IC50 value up to 0.53 µM, providing a promising lead compound for new anti-glioma drug development. Mechanistic analyses showed that 13e suppressed the MDM4 protein expression, upregulated the p53 protein level, and induced cell cycle arrest at G2/M phase and apoptosis based on Western blot and flow cytometry assays.


Assuntos
Antineoplásicos , Apoptose , Glioblastoma , Proteína Supressora de Tumor p53 , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antracenos/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Proteínas Proto-Oncogênicas/metabolismo , Proteínas de Ciclo Celular/metabolismo
4.
Fish Shellfish Immunol ; 139: 108912, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37353063

RESUMO

Temperature is an essential environmental factor for the survival of aquatic animals. Low temperature stress can induce mitochondria to produce excessive ROS and free radicals, and destroy homeostasis. c-Jun N-terminal kinase (JNK) is involved in regulating various physiological processes, including inflammatory responses, cell cycle, reproduction, and apoptosis. Here, we investigated the mechanism of ROS/JNK pathway under low temperature stress both in vitro and in vivo. In this study, transcriptome analysis revealed that apoptosis, autophagy, calcium channel, and antioxidant were involved in the mediation of low temperature tolerance in Pacific white shrimp (penaeus vannamei). PvJNK was activated in response to low temperature stress. Treatments with different temperature caused oxidative stress as demonstrated by increased intensity of the ROS indicator H2DCF-DA, and induced apoptosis as confirmed by indicator FITC. Pretreatment with N-acetylcysteine, an ROS scavenger, attenuated low temperature induced apoptosis, and inhibited the expression of PvJNK. In addition, we demonstrate that mediator PvJNK translocated to nuclear through interacting with PvRheb. By using flow cytometry, inhibiting PvJNK can increase the expression of apoptosis related genes, accelerate tissue damage, and induce ROS and cell apoptosis. The ultimate inhibition of PvJNK accelerates the mortality of shrimp under low temperature stress. Overall, these findings suggest that during low temperature stress, PvJNK was activated by ROS to regulates apoptosis via interacting with PvRheb to promote PvJNK into the nucleus and to improve low temperature tolerance of shrimp.


Assuntos
Proteínas Quinases JNK Ativadas por Mitógeno , Penaeidae , Animais , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Espécies Reativas de Oxigênio/metabolismo , Penaeidae/genética , Penaeidae/metabolismo , Temperatura , Apoptose/genética
5.
Macromol Rapid Commun ; 44(3): e2200690, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36250440

RESUMO

Water-soluble 3D polymers with inherent nanoscale pores have been shown to be ideal platforms for the inclusion and delivery of drugs and hold a great promise as biocompatible materials for diagnostic and therapeutic purposes. Herein, a low cytotoxic water-soluble flexible organic framework FOF-S6 with a hydrodynamic diameter of about 127.5 nm is synthesized through the formation of a hydrazone bond from a semirigid tetraaldehyde and a flexible biacylhydrazines which contains a disulfide bond (1:2). FOF-S6 has the ability to dissociate and release inclusion complexes in response to weakly acidic media and glutathione (GSH) overexpressed in tumor cells. More importantly, a facile strategy is developed to contain and deliver aggregation-induced emission photosensitizers (AIE PS, TBD-DQA-540) and chemotherapeutic drugs (Doxorubicin hydrochloride, DOX). DOX-PS@FOF-S6 is synthesized by a one-pot method, which can realize efficient photo-chemotherapy under the guidance of fluorescence imaging, thereby improving the multidrug resistance of tumor cells and the instability of photosensitizers, so as to improve the tumor treatment efficacy.


Assuntos
Neoplasias , Fármacos Fotossensibilizantes , Humanos , Fármacos Fotossensibilizantes/química , Água , Doxorrubicina/química , Neoplasias/tratamento farmacológico , Glutationa , Oxirredução , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral
6.
Int J Mol Sci ; 25(1)2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38203354

RESUMO

Bacterial wilt, caused by Ralstonia solanacearum, one of the most destructive phytopathogens, leads to significant annual crop yield losses. Type III effectors (T3Es) mainly contribute to the virulence of R. solanacearum, usually by targeting immune-related proteins. Here, we clarified the effect of a novel E3 ubiquitin ligase (NEL) T3E, RipAW, from R. solanacearum on pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and further explored its action mechanism. In the susceptible host Arabidopsis thaliana, we monitored the expression of PTI marker genes, flg22-induced ROS burst, and callose deposition in RipAW- and RipAWC177A-transgenic plants. Our results demonstrated that RipAW suppressed host PTI in an NEL-dependent manner. By Split-Luciferase Complementation, Bimolecular Fluorescent Complimentary, and Co-Immunoprecipitation assays, we further showed that RipAW associated with three crucial components of the immune receptor complex, namely FLS2, XLG2, and BIK1. Furthermore, RipAW elevated the ubiquitination levels of FLS2, XLG2, and BIK1, accelerating their degradation via the 26S proteasome pathway. Additionally, co-expression of FLS2, XLG2, or BIK1 with RipAW partially but significantly restored the RipAW-suppressed ROS burst, confirming the involvement of the immune receptor complex in RipAW-regulated PTI. Overall, our results indicate that RipAW impairs host PTI by disrupting the immune receptor complex. Our findings provide new insights into the virulence mechanism of R. solanacearum.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ralstonia solanacearum , Complexo Antígeno-Anticorpo , Reconhecimento da Imunidade Inata , Espécies Reativas de Oxigênio , Imunoprecipitação , Receptores Imunológicos , Proteínas Serina-Treonina Quinases , Proteínas de Arabidopsis/genética
7.
Opt Express ; 30(10): 16229-16241, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-36221471

RESUMO

In this work, we design an ultrathin 2-bit anisotropic Huygens coding metasurface (AHCM) composed by bilayer metallic square-ring structures for flexible manipulation of the terahertz wave. Based on the polarized-dependent components of electric surface admittance and magnetic surface impedance, we confirm that both the electric and magnetic resonances on coding meta-atoms are excited, so as to provide a full phase coverage and significantly low reflection. By encoding the elements with distinct coding sequences, the x- and y-polarized incident waves are anomalously refracted into opposite directions. More uniquely, we also demonstrate that the designed AHCM can be utilized as a transmission-type quarter-wave plate. The proposed metasurface paves a new way toward multifunctional terahertz wavefront manipulation.

8.
Appl Opt ; 61(26): 7558-7564, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36256353

RESUMO

A reconfigurable anisotropic coding metasurface composed of a graphene layer and anisotropic Jerusalem-cross metallic layer is proposed for dynamic and complete multi-channel terahertz wavefront manipulation. By controlling the Fermi energy of graphene, continuous amplitude modulation is realized for the coding elements with certain phase responses. By arranging anisotropic phase coding elements with a specific coding sequence and changing the Fermi energy of graphene, the proposed metasurface can dynamically control multi-channel reflection beams with designed power distribution and simultaneously manipulate the scattering pattern from diffusion to mirror scattering under x- and y-polarized incidence, respectively. Compared with the dynamic phase modulation metasurface, such a tunable metasurface uses three degrees of freedom, including the polarization, phase, and amplitude responses to fully control the reflected wavefronts, which may have promising applications in tunable terahertz multi-functional holograms and multi-channel information communication.

9.
Int J Mol Sci ; 23(23)2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36499365

RESUMO

RING-finger-type ubiquitin E3 ligase Constitutively Photomorphogenic 1 (COP1) and floral integrators such as FLOWERING LOCUS T (FT), TWIN SISTER OF FT (TSF) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) have been identified as regulators of stomatal movement. However, little is known about their roles and relationship in dark-induced stomatal closure. Here, we demonstrated that COP1 is required for dark-induced stomatal closure using cop1 mutant. The cop1 mutant closed stomata in response to exogenous nitric oxide (NO) but not hydrogen peroxide (H2O2), and H2O2 but not NO accumulated in cop1 in darkness, further indicating that COP1 acts downstream of H2O2 and upstream of NO in dark-induced stomatal closure. Expression of FT, TSF and SOC1 in wild-type (WT) plants decreased significantly with dark duration time, but this process was blocked in cop1. Furthermore, ft, tsf, and soc1 mutants accumulated NO and closed stomata faster than WT plants in response to darkness. Altogether, our results indicate that COP1 transduces H2O2 signaling, promotes NO accumulation in guard cells by suppressing FT, TSF and SOC1 expression, and consequently leads to stomatal closure in darkness. These findings add new insights into the mechanisms of dark-induced stomatal closure.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Óxido Nítrico/metabolismo , Estômatos de Plantas/metabolismo , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Regulação da Expressão Gênica de Plantas , Proteína de Ligação a Fosfatidiletanolamina/genética
10.
Molecules ; 27(3)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35163951

RESUMO

Phosphorus in the form of phosphate (Pi) is an essential element for metabolic processes, including lipid metabolism. In yeast, the inositol polyphosphate kinase vip1 mediated synthesis of inositol heptakisphosphate (IP7) regulates the phosphate-responsive (PHO) signaling pathway, which plays an important role in response to Pi stress. The role of vip1 in Pi stress and lipid metabolism of Candida albicans has not yet been studied. We found that when vip1Δ/Δ was grown in glucose medium, if Pi was supplemented in the medium or mitochondrial Pi transporter was overexpressed in the strain, the lipid droplet (LD) content was reduced and membrane damage was alleviated. However, further studies showed that neither the addition of Pi nor the overexpression of the Pi transporter affected the energy balance of vip1Δ/Δ. In addition, the LD content of vip1Δ/Δ grown in Pi limitation medium PNMC was lower than that grown in SC, and the metabolic activity of vip1Δ/Δ grown in PNMC was also lower than that grown in SC medium. This suggests that the increase in Pi demand by a high energy metabolic rate is the cause of LD accumulation in vip1Δ/Δ. In addition, in the vip1Δ/Δ strains, the core transcription factor PHO4 in the PHO pathway was transported to the vacuole and degraded, which reduced the pathway activity. However, this does not mean that knocking out vip1 completely blocks the activation of the PHO pathway, because the LD content of vip1Δ/Δ grown in the medium with ß-glycerol phosphate as the Pi source was significantly reduced. In summary, the increased Pi demand and the decreased PHO pathway activity in vip1Δ/Δ ultimately lead to LD accumulation and cell membrane damage.


Assuntos
Metabolismo Energético/fisiologia , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , Candida albicans/metabolismo , Membrana Celular/metabolismo , Expressão Gênica/genética , Regulação Fúngica da Expressão Gênica/genética , Fosfatos de Inositol , Gotículas Lipídicas/metabolismo , Fosfatos/metabolismo , Fosforilação , Fosfotransferases (Aceptor do Grupo Fosfato)/fisiologia , Transdução de Sinais , Fatores de Transcrição/metabolismo , Vacúolos/metabolismo
11.
Opt Express ; 29(11): 17258-17268, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34154271

RESUMO

Polarization modulation and multichannel beam generation are crucial in multichannel communication and high-resolution imaging at THz frequency. In this work, we present a polarization-reprogrammable coding metasurface composed of VO2/Au composite concentric rings (CCRs). Owing to the phase-change property of VO2, the CCR is designed as a digital coding element for the polarization conversion. When VO2 remains insulator state at room temperature, the y-polarized incident wave is transformed into x-polarized wave, which can be regarded as digital state 0. When VO2 converts into metal state at critical temperature (68 °C), the polarization of reflected wave stays unchanged, corresponding to digital state 1. Any desired linear polarization state of reflected beam is achieved by taking advantage of different coding sequences in a programmable manner. Furthermore, by combining phase gradient with polarization coding states, we propose an anisotropic programmable metasurface to control the multi-channel reflected beams dynamically. By arranging distinct coding sequences, we show that the EM reflected beams can be manipulated flexibly. The proposed programmable metasurface paves new ways towards THz polarization manipulation, signal detection and information communication.

12.
Pharmacol Res ; 165: 105460, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33513357

RESUMO

Despite of its high morbidity and mortality, there is still a lack of effective treatment for ischemic stroke in part due to our incomplete understanding of molecular mechanisms of its pathogenesis. In this study, we demonstrate that SHH-PTCH1-GLI1-mediated axonal guidance signaling and its related neurogenesis, a central pathway for neuronal development, also plays a critical role in early stage of an acute stroke model. Specifically, in vivo, we evaluated the effect of GXNI on ischemic stroke mice via using the middle cerebral artery embolization model, and found that GXNI significantly alleviated cerebral ischemic reperfusion (I/R) injury by reducing the volume of cerebral infarction, neurological deficit score and cerebral edema, reversing the BBB permeability and histopathological changes. A combined approach of RNA-seq and network pharmacology analysis was used to reveal the underlying mechanisms of GXNI followed by RT-PCR, immunohistochemistry and western blotting validation. It was pointed out that axon guidance signaling pathway played the most prominent role in GXNI action with Shh, Ptch1, and Gli1 genes as the critical contributors in brain protection. In addition, GXNI markedly prevented primary cortical neuron cells from oxygen-glucose deprivation/reoxygenation damage in vitro, and promoted axon growth and synaptogenesis of damaged neurons, which further confirmed the results of in vivo experiments. Moreover, due to the inhibition of the SHH-PTCH1-GLI1 signaling pathway by cyclopropylamine, the effect of GXNI was significantly weakened. Hence, our study provides a novel option for the clinical treatment of acute ischemic stroke by GXNI via SHH-PTCH1-GLI1-mediated axonal guidance signaling, a neuronal development pathway previously considered for after-stroke recovery.


Assuntos
Orientação de Axônios/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/patologia , Animais , Animais Recém-Nascidos , Orientação de Axônios/fisiologia , Isquemia Encefálica/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , AVC Isquêmico/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
13.
Int Wound J ; 17(2): 285-299, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31724831

RESUMO

Bacterial infection is a common wound complication that can significantly delay healing. Classical local therapies for infected wounds are expensive and are frequently ineffective. One alternative therapy is photodynamic therapy (PDT). We conducted a systematic review to clarify whether PDT is useful for bacteria-infected wounds in animal models. PubMed and Medline were searched for articles on PDT in infected skin wounds in animals. The language was limited to English. Nineteen articles met the inclusion criteria. The overall study methodological quality was moderate, with a low-moderate risk of bias. The animal models were mice and rats. The wounds were excisional, burn, and abrasion wounds. Wound size ranged from 6 mm in diameter to 1.5 × 1.5 cm2 . Most studies inoculated the wounds with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. Eleven and 17 studies showed that the PDT of infected wounds significantly decreased wound size and bacterial counts, respectively. Six, four, and two studies examined the effect of PDT on infected wound-cytokine levels, wound-healing time, and body weight, respectively. Most indicated that PDT had beneficial effects on these variables. PDT accelerated bacteria-infected wound healing in animals by promoting wound closure and killing bacteria.


Assuntos
Antibacterianos/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Fotoquimioterapia/métodos , Lesões dos Tecidos Moles/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Animais , Modelos Animais de Doenças , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/microbiologia , Infecção dos Ferimentos/microbiologia
14.
Lasers Surg Med ; 51(4): 332-338, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30136732

RESUMO

BACKGROUND: Dissecting cellulitis of the scalp (DCS) is difficult to be treated and 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) is considered to be a potential treatment for inflammatory skin diseases. OBJECTIVE: To analyze the efficacy and safety of ALA-PDT on DCS. MATERIALS AND METHODS: The treatment areas of DCS patients were incubated with freshly prepared 10% ALA for 3 hours. The 633 ± 10 nm light with the intensity of 80-100 mw/cm2 was used as the irradiation source of ALA-PDT, and the irradiation time was 20-30 minutes. Three sessions were applied at an interval of 10-15 days. According to the reduction of lesions and the improvements of patients' symptoms after each session, the objective assessment of therapeutic effect was divided into four grades. The adverse effects were recorded. RESULTS: Seven male DCS patients finished the treatments and assessments. One month after three sessions of treatment, one patient recovered, three patients received significant improvement, and one patients received medium improvement. At the 3-month follow-up, two patients recovered, four patients received significant improvement, and one patients received medium improvement. The patients tolerated well to the therapy without any severe adverse effects. CONCLUSION: 10% ALA-PDT is effective and safe on male DCS patients. As a localized and less invasive treatment, it provides a preferable choice for DCS patients. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.


Assuntos
Ácido Aminolevulínico/uso terapêutico , Celulite (Flegmão)/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Dermatoses do Couro Cabeludo/tratamento farmacológico , Dermatopatias Genéticas/tratamento farmacológico , Adolescente , Adulto , Esquema de Medicação , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
15.
Sensors (Basel) ; 19(8)2019 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-31010066

RESUMO

In this paper, a fixed-point iterative filter developed from the classical extended Kalman filter (EKF) was proposed for general nonlinear systems. As a nonlinear filter developed from EKF, the state estimate was obtained by applying the Kalman filter to the linearized system by discarding the higher-order Taylor series items of the original nonlinear system. In order to reduce the influence of the discarded higher-order Taylor series items and improve the filtering accuracy of the obtained state estimate of the steady-state EKF, a fixed-point function was solved though a nested iterative method, which resulted in a fixed-point iterative filter. The convergence of the fixed-point function is also discussed, which provided the existing conditions of the fixed-point iterative filter. Then, Steffensen's iterative method is presented to accelerate the solution of the fixed-point function. The final simulation is provided to illustrate the feasibility and the effectiveness of the proposed nonlinear filtering method.

16.
Biol Blood Marrow Transplant ; 23(2): 255-261, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27888016

RESUMO

Lapses in the prevention of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) warrant novel approaches. Such approaches include, among others, the use of post-transplantation cyclophosphamide (PTC) and proteasome inhibitors. Although PTC alone consistently produces low rates of chronic GVHD, the incidence of acute GVHD remains significant. Inversely, prolonged post-transplantation administration of proteasome inhibitors carries a risk of paradoxical aggravation of GVHD. We examined whether the combination of cyclophosphamide and ixazomib addresses the limitations of each of these agents when used alone to prevent GVHD in mice subjected to allogeneic HSCT across MHC barriers. We chose ixazomib, an orally bioavailable proteasome inhibitor, because of its favorable physiochemical characteristics. The combination of cyclophosphamide and ixazomib improved overall survival of mice in comparison to an untreated control group and to groups receiving either cyclophosphamide alone or ixazomib alone. Furthermore, cyclophosphamide prevented the surge of IL-1ß, GVHD aggravation, and sudden death associated with prolonged administration of ixazomib after HSCT. Finally, we demonstrated that although ixazomib was administered before cyclophosphamide, it did not impair the preferential depletion of proliferating as opposed to resting donor T cells. Our data suggest that the combination of cyclophosphamide and ixazomib for the prevention of GVHD after allogeneic HSCT is promising and merits further investigation in clinical trials.


Assuntos
Compostos de Boro/uso terapêutico , Ciclofosfamida/uso terapêutico , Glicina/análogos & derivados , Doença Enxerto-Hospedeiro/prevenção & controle , Inibidores de Proteassoma/uso terapêutico , Animais , Transplante de Medula Óssea/efeitos adversos , Compostos de Boro/administração & dosagem , Compostos de Boro/farmacologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/farmacologia , Citocinas/sangue , Esquema de Medicação , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Glicina/administração & dosagem , Glicina/farmacologia , Glicina/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/patologia , Intestino Delgado/patologia , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Inibidores de Proteassoma/administração & dosagem , Inibidores de Proteassoma/farmacologia , Quimera por Radiação , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/transplante
17.
Appl Microbiol Biotechnol ; 101(8): 3077-3088, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28293710

RESUMO

The human intestine hosts various complex microbial communities that are closely associated with multiple health and disease processes. Determining the composition and function of these microbial communities is critical to unveil disease mechanisms and promote human health. Recently, meta-omic strategies have been developed that use high-throughput techniques to provide a wealth of information, thus accelerating the study of gut microbes. Metaproteomics is a newly emerged analytical approach that aims to identify proteins on a large scale in complex environmental microbial communities (e.g., the gut microbiota). This review introduces the recent analytical strategies and applications of metaproteomics, with a focus on advances in gut microbiota research, including a discussion of the limitations and challenges of these approaches.


Assuntos
Proteínas de Bactérias/isolamento & purificação , Microbioma Gastrointestinal , Metagenoma , Proteômica , Proteínas de Bactérias/genética , Pesquisa Biomédica , Microbioma Gastrointestinal/genética , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Espectrometria de Massas , Proteoma/genética , Proteoma/metabolismo
18.
Biol Blood Marrow Transplant ; 21(4): 604-11, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25240817

RESUMO

Cyclophosphamide's lack of hematopoietic stem cell toxicity and its unique effects on the immune system have prompted several investigators to explore its potential for the prevention of graft-versus-host disease (GVHD). In haploidentical hematopoietic stem cell transplants, post-transplant cyclophosphamide together with standard prophylaxis reduces the incidence of GVHD to acceptable rates without the need for T cell depletion. In matched related and unrelated donor settings, cyclophosphamide alone has produced encouraging results. In particular, the low incidence of chronic GVHD is noteworthy. Here, we present a review of the current understanding of the mechanism of action of post-transplant cyclophosphamide and summarize the clinical data on its use for the prevention of GVHD.


Assuntos
Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Depleção Linfocítica , Doadores não Relacionados , Aloenxertos , Doença Enxerto-Hospedeiro/etiologia , Humanos
19.
Artigo em Inglês | MEDLINE | ID: mdl-38896519

RESUMO

Restoring high-quality images from degraded hazy observations is a fundamental and essential task in the field of computer vision. While deep models have achieved significant success with synthetic data, their effectiveness in real-world scenarios remains uncertain. To improve adaptability in real-world environments, we construct an entirely new computational framework by making efforts from three key aspects: imaging perspective, structural modules, and training strategies. To simulate the often-overlooked multiple degradation attributes found in real-world hazy images, we develop a new hazy imaging model that encapsulates multiple degraded factors, assisting in bridging the domain gap between synthetic and real-world image spaces. In contrast to existing approaches that primarily address the inverse imaging process, we design a new dehazing network following the "localization-and-removal" pipeline. The degradation localization module aims to assist in network capture discriminative haze-related feature information, and the degradation removal module focuses on eliminating dependencies between features by learning a weighting matrix of training samples, thereby avoiding spurious correlations of extracted features in existing deep methods. We also define a new Gaussian perceptual contrastive loss to further constrain the network to update in the direction of the natural dehazing. Regarding multiple full/no-reference image quality indicators and subjective visual effects on challenging RTTS, URHI, and Fattal real hazy datasets, the proposed method has superior performance and is better than the current state-of-the-art methods. See more results: https://github.com/fyxnl/KA Net.

20.
Heliyon ; 10(11): e31990, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38912436

RESUMO

The tourism network attention as a reflection of tourism demand is closely related to the tourism flow, the differences between the two has become an important criterion for judging the efficiency of destination tourism demand conversion, as well as a manifestation of the balance and coordination of destination tourism industry. Against the background of insufficient release of tourism demand in China, research on the development differences between tourism network attention and tourism flow can provide a basis for demand-side management and high-quality development. Based on the theory of spatial mismatch, this research analyzes the spatial development difference between the tourism network attention and the tourism flow in Shanghai from 2012 to 2021 using methods such as center of gravity model, spatial mismatch index, and two-dimensional combination matrix. The results show: (1) According to the analysis of the center of gravity model, there was a shift of the center of gravity of tourism network attention with the direction of "south-north", while the tourism flow shifted "west-east"; the center of gravity between tourism network attention and tourism flow began to diverge from 2012 to 2016, gradually converged from 2016 to 2019, and then gradually deviated again after 2020. (2) According to the spatial mismatch index, the spatial mismatch types between tourism network attention and tourism flow in various Districts of Shanghai are mainly negative and low mismatch, with high mismatch areas mainly distributed in the eastern and southwestern parts of Shanghai. (3) Combining the two-dimensional combination matrix, it can be observed that the spatial development difference between tourism network attention and tourism flow in Shanghai show a characteristic of "enlarging-shrinking-enlarging". From 2012 to 2016, the spatial development difference between tourism network attention and tourism flow in Shanghai continuously expanded; from 2017 to 2019, the spatial development difference continuously shrank; and from 2020 to 2021, the spatial differences expanded again. (4) The analysis results of the panel data model show that the development of tourism resources and the level of tourism services have a positive promoting effect on the evolution of spatial mismatch, while the social basic development environment has a negative effect. The research results not only meet the needs of evaluating the high-quality development of the tourism industry in the current economic restructuring, providing direction for the high-quality development of the regional tourism industry, but also enrich the research content of network attention as a tourism element participating in the evaluation of tourism industry development quality, and deepen the relationship research between network attention and tourism flow.

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