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1.
Opt Express ; 32(7): 12476-12495, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571069

RESUMO

Multi-band terahertz (THz) absorbers have recently gained attention due to their favorable application prospects in communication, imaging, detection, and other fields. However, many multi-band THz absorbers are tuned by a single method, which limits their tuning effect. To address this issue, we propose a multi-band THz absorber that can be co-modulated by thermal and electrical methods. Our proposed absorber uses vanadium dioxide (VO2) to achieve this co-modulation. When VO2 is insulating, the frequency of the absorbing peaks originating from the lateral Fabry-Pérot resonance mode can be changed by adjusting the VO2 width. When VO2 is a conductor, the quality factor of the absorbing peak based on the inductor-capacitor resonance mode can be tuned by adjusting the width of VO2. By varying the top dielectric layer thickness, the frequency of the absorbing peaks can be tuned over a wide range. For devices with two or three layers of graphene nanoribbons-dielectric stacks, a modulation effect similar to that of varying dielectric layer thickness in a single-layer graphene device can be achieved simply by applying a 1 eV Fermi energy to graphene nanoribbons in different layers. By combining thermal and electrical modulation, the two or three-layer stacked device can be dynamically switched between four or six absorbing states, and a wider range of dynamic peak frequency modulation can be realized. Furthermore, the performance of the absorber does not deteriorate significantly at an incident angle of up to 70°. Our proposed thermal-electrical switchable wide-angle multi-band THz absorber provides a reference for the design, fabrication, and application of high-performance THz absorbers in different fields.

2.
Appl Microbiol Biotechnol ; 108(1): 214, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363425

RESUMO

Glucosylglycerol (GG) is a natural compatible solute that can be synthesized by many cyanobacteria and a few heterotrophic bacteria under high salinity conditions. In cyanobacteria, GG is synthesized by GG-phosphate synthase and GG-phosphate phosphatase, and a hydrolase GGHA catalyzes its degradation. In heterotrophic bacteria (such as some Marinobacter species), a fused form of GG-phosphate phosphatase and GG-phosphate synthase is present, but the cyanobacteria-like degradation pathway is not available. Instead, a phosphorylase GGP, of which the coding gene is located adjacent to the gene that encodes the GG-synthesizing enzyme, is supposed to perform the GG degradation function. In the present study, a GGP homolog from the salt-tolerant M. salinexigens ZYF650T was characterized. The recombinant GGP catalyzed GG decomposition via a two-step process of phosphorolysis and hydrolysis in vitro and exhibited high substrate specificity toward GG. The activity of GGP was enhanced by inorganic salts at low concentrations but significantly inhibited by increasing salt concentrations. While the investigation on the physiological role of GGP in M. salinexigens ZYF650T was limited due to the failed induction of GG production, the heterologous expression of ggp in the living cells of the GG-producing cyanobacterium Synechocystis sp. PCC 6803 significantly reduced the salt-induced GG accumulation. Together, these data suggested that GGP may represent a novel pathway of microbial GG catabolism. KEY POINTS: • GGP catalyzes GG degradation by a process of phosphorolysis and hydrolysis • GGP-catalyzed GG degradation is different from GGHA-based GG degradation • GGP represents a potential novel pathway of microbial GG catabolism.


Assuntos
Glucosídeos , Fosforilases , Synechocystis , Fosforilases/química , Monoéster Fosfórico Hidrolases/genética , Fosfatos
3.
Clin Endocrinol (Oxf) ; 99(1): 92-102, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37029081

RESUMO

OBJECTIVE: Parapharyngeal metastases (PPM) are rarely observed in patients with well-differentiated thyroid cancer (WDTC). Radioiodine (131 I) therapy has been the main treatment for metastatic and recurrent DTC after thyroidectomy. This study was performed to evaluate the clinicopathological features and long-term outcomes associated with survival of patients with PPM at the end of follow-up. DESIGN: In total, 14,984 consecutive patients with DTC who underwent 131 I therapy after total or near-total thyroidectomy from 2004 to 2021 were retrospectively reviewed. Therapeutic efficacy was evaluated using the Response Evaluation Criteria in Solid Tumours v1.1 and logistic regression analysis. The disease status was determined using dynamic risk stratification. Disease-specific survival (DSS) was assessed using the Kaplan-Meier method and a Cox proportional hazards model. PATIENTS: Seventy-five patients with PPM from WDTC were enroled in this study. Their median age at the initial diagnosis of PPM was 40.2 ± 14.1 years, and the patients comprised 32 men and 43 women (male:female ratio, 1.00:1.34). Of the 75 patients, 43 (57.33%) presented with combined distant metastases. Fifty-seven (76.00%) patients had 131 I avidity and 18 had non-131 I avidity. At the end of follow-up, 22 (29.33%) patients showed progressive disease. Sixteen of the 75 patients died; of the remaining 59 patients, 6 (8.00%) had an excellent response, 6 (8.00%) had an indeterminate response, 10 (13.33%) had an biochemical incomplete response, and 37 (49.33%) had a structural incomplete response. Multivariate analysis confirmed that age at initial PPM diagnosis, the maximal size of PPM, and 131 I avidity had significant effects on progressive disease of PPM lesions (p = .03, p= .02, and p < .01, respectively). The 5- and 10-year DSS rates were 98.49% and 62.10%, respectively. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with a poor prognosis (p = .03 and p = .04, respectively). CONCLUSION: The therapeutic effect for PPM was closely associated with 131 I avidity, age at initial PPM diagnosis, and maximal size of PPM at the end of follow-up. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with poor survival.


Assuntos
Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Seguimentos , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia
4.
Skin Res Technol ; 29(6): e13389, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37357650

RESUMO

BACKGROUND: Keloids and hypertrophic scars frustrate patients by the deformity of appearance and organ dysfunction. Many modalities had been tried in clinic practice, but the results are unsatisfied. OBJECTIVE: We retrospectively analysed the combined application of bleomycin and triamcinolone for the treatment of keloids and hypertrophic scars. METHODS: The combination of bleomycin and triamcin acetonide was applied to the treatment of keloids and hypertrophic scars, 86 cases accepted the treatment. Follow-up 2-5 years after treatment. RESULTS: (1) The pain of scars and itching symptoms have basically subsided through treatment. (2) After drug injection treatment, the keloid began to shrink, some of the keloids disappeared. (3) Small keloids did not recur after treatment. Large keloids had local recurrence after treatment. When further treatment was given, the recurrence disappeared. CONCLUSION: The combined application of bleomycin and triamcin acetonide can effectively cure keloids and hypertrophic scars.


Assuntos
Cicatriz Hipertrófica , Queloide , Humanos , Queloide/tratamento farmacológico , Queloide/patologia , Cicatriz Hipertrófica/tratamento farmacológico , Cicatriz Hipertrófica/patologia , Bleomicina/uso terapêutico , Triancinolona/uso terapêutico , Estudos Retrospectivos , Injeções Intralesionais , Resultado do Tratamento
5.
Anal Chem ; 94(23): 8433-8440, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35621827

RESUMO

The development of monitoring methods to capture short-lived intermediates is crucial for kinetic mechanism validation of enzymatic reaction steps. In this work, a semisynthetic selenoenzyme nanoreactor was constructed by introducing the unnatural amino acid (Sec) into the lumen of the α-hemolysin (αHL) nanopore. This nanoreactor not only created a highly confined space to trap the enzyme-substrate complex for a highly efficient antioxidant activity but also provided a single channel to characterize a series of selenoenzyme intermediates in the whole catalytic cycle through electrochemical analysis. In particular, the unstable intermediate of SeOH can be clearly detected by the characteristic blocking current. The duration time corresponding to the lifetime of each intermediate that stayed within the nanopore was also determined. This label-free approach showed a high detection sensitivity and temporal-spatial resolution to scrutinize a continuous enzymatic process, which would facilitate uncovering the mysteries of selenoenzyme catalysis at the single-molecule level.


Assuntos
Proteínas Hemolisinas , Nanoporos , Proteínas Hemolisinas/química , Cinética , Nanotecnologia
6.
Appl Environ Microbiol ; 88(7): e0006022, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35285711

RESUMO

Bacterial porin-encoding genes are often found under positive selection. Local recombination has also been identified in a few of them to facilitate bacterial rapid adaptation, although it remains unknown whether it is a common evolutionary mechanism for the porins or outer membrane proteins in Gram-negative bacteria. In this study, we investigated the beta-barrel (ß-barrel) porin-encoding genes in Escherichia coli that were reported under positive Darwinian selection. Besides fhuA that was found with ingenic local recombination previously, we identified four other genes, i.e., lamB, ompA, ompC, and ompF, all showing the similar mosaic evolution patterns. Comparative analysis of the protein sequences disclosed a list of highly variable regions in each family, which are mostly located in the convex of extracellular loops and coinciding with the binding sites of bacteriophages. For each of the porin families, mosaic recombination leads to unique combinations of the variable regions with different sequence patterns, generating diverse protein groups. Structural modeling indicated a conserved global topology among the different porins, with the extracellular surface varying a lot due to individual or combinatorial variable regions. The conservation of global tertiary structure would ensure the channel activity, while the wide diversity of variable regions may represent selection to avoid the invasion of phages, antibiotics or immune surveillance factors. Our study identified multiple bacterial porin genes with mosaic evolution. We hypothesize that this could be generalized strategy for outer membrane proteins to both maintain normal life processes and evade the attack of unfavored factors rapidly. IMPORTANCE Microevolution studies can disclose more elaborate evolutionary mechanisms of genes, appearing especially important for genes with multifaceted function such as those encoding outer membrane proteins. However, in most cases, the gene is considered as a whole unit, and the evolutionary patterns are disclosed. Here, we report that multiple bacterial porin proteins follow mosaic evolution, with local ingenic recombination combined with spontaneous mutations based on positive Darwinian selection, and conservation for most structural regions. This could represent a common mechanism for bacterial outer membrane proteins. The variable regions within each porin family showed large coincidence with the binding sites of bacteriophages, antibiotics, and immune factors and therefore would represent effective targets for the development of new antibacterial agents or vaccines.


Assuntos
Escherichia coli , Porinas , Animais , Antibacterianos/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Porinas/genética , Porinas/metabolismo , Ovinos
7.
Chem Rev ; 120(8): 3787-3851, 2020 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-32202104

RESUMO

Immuno-positron emission tomography (immunoPET) is a paradigm-shifting molecular imaging modality combining the superior targeting specificity of monoclonal antibody (mAb) and the inherent sensitivity of PET technique. A variety of radionuclides and mAbs have been exploited to develop immunoPET probes, which has been driven by the development and optimization of radiochemistry and conjugation strategies. In addition, tumor-targeting vectors with a short circulation time (e.g., Nanobody) or with an enhanced binding affinity (e.g., bispecific antibody) are being used to design novel immunoPET probes. Accordingly, several immunoPET probes, such as 89Zr-Df-pertuzumab and 89Zr-atezolizumab, have been successfully translated for clinical use. By noninvasively and dynamically revealing the expression of heterogeneous tumor antigens, immunoPET imaging is gradually changing the theranostic landscape of several types of malignancies. ImmunoPET is the method of choice for imaging specific tumor markers, immune cells, immune checkpoints, and inflammatory processes. Furthermore, the integration of immunoPET imaging in antibody drug development is of substantial significance because it provides pivotal information regarding antibody targeting abilities and distribution profiles. Herein, we present the latest immunoPET imaging strategies and their preclinical and clinical applications. We also emphasize current conjugation strategies that can be leveraged to develop next-generation immunoPET probes. Lastly, we discuss practical considerations to tune the development and translation of immunoPET imaging strategies.


Assuntos
Técnicas Imunológicas/métodos , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Animais , Anticorpos Monoclonais/imunologia , Antígenos de Neoplasias/imunologia , Linhagem Celular Tumoral , Humanos , Neoplasias/imunologia , Compostos Radiofarmacêuticos/imunologia , Anticorpos de Domínio Único/imunologia
8.
Cancer Sci ; 112(3): 997-1010, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33247999

RESUMO

Programmed cell death ligand 1 (PD-L1), inducing T cell exhaustion to facilitate immune escape of tumor cells, is upregulated by interleukin 6 (IL-6) in T cell lymphoma and ovarian cancer. The purpose of this study is to investigate the expression of IL-6 and PD-L1 in thyroid cancer, and whether IL-6 regulates PD-L1 expression. As a result, IL-6 and PD-L1 were highly expressed in thyroid cancer tissues. Multivariate logistic analysis showed that tumor size, distant metastasis, and risk stratification were significantly associated with IL-6 expression (P < .05), and multifocality, lymph node metastasis, distant metastasis, risk stratification, and IL-6 expression were identified as the independent predictors of PD-L1 expression (P < .05). The invasiveness of thyroid cancer was significantly enhanced after IL-6 treatment or PD-L1 overexpression. PD-L1 positive rate correlated with IL-6 expression in cancer tissues (P < .001), and after IL-6 treatment, the PD-L1 expression in TPC-1 and BCPAP significantly increased. The mitogen-activated protein kinase pathway (MAPK) and the Janus-activated kinase (JAK)-signal transducers and activators of transcription 3 (STAT3) signaling pathways were activated by IL-6, and the IL-6-induced PD-L1 expression decreased after treatment with these two signaling pathway inhibitors. Knockdown of transcription factors c-Jun and stat3 suppressed the expression of PD-L1 induced by IL-6, and these two factors could bind to PD-L1 gene promoter directly and promote its transcription. It is concluded that IL-6 and PD-L1 are overexpressed in thyroid cancer and are related to tumor invasiveness. IL-6 upregulates PD-L1 expression through the MAPK and JAK-STAT3 signaling pathways, which function via transcription factors c-Jun and stat3.


Assuntos
Adenocarcinoma Folicular/genética , Antígeno B7-H1/genética , Interleucina-6/metabolismo , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/patologia , Adulto , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Janus Quinases/genética , Janus Quinases/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-jun/genética , Proteínas Proto-Oncogênicas c-jun/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Câncer Papilífero da Tireoide/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
9.
Appl Environ Microbiol ; 86(7)2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-31953341

RESUMO

Salinity is one of the most important abiotic factors in various natural habitats of microbes. Cyanobacteria are the most widely distributed family of photosynthetic microorganisms in environments with fluctuating salinity. In response to salt stress, many cyanobacteria de novo synthesize compatible solutes to maintain osmotic balance in the cell. However, the regulation of intracellular accumulation of these compounds is still not well understood. The freshwater cyanobacterium Synechococcus elongatus PCC 7942 (Syn7942) exclusively accumulates sucrose as a compatible solute upon salt stress and is thus an ideal model microorganism for studying the metabolism of compatible solute dynamics. Here, we focused on elucidating the regulatory mechanisms involved in salt-induced sucrose accumulation in Syn7942. Using a series of physiological and biochemical experiments, we showed that the ionic effect of salt stress plays an important role in inducing sucrose synthesis, whereby elevated ion concentration directly activates the sucrose-synthesizing enzyme sucrose-phosphate synthase and simultaneously inhibits the sucrose-degrading enzyme invertase, resulting in a rapid sucrose accumulation. Thus, we propose a novel mechanism for cyanobacterial adaption to salt stress and fluctuating salinity, i.e., the ion-induced synergistic modulation of the enzymes synthesizing and degrading compatible solutes. These findings greatly enhance our current understanding of microbial adaptation to salt.IMPORTANCE Most microbes de novo synthesize compatible solutes for adaptation to salt stress or fluctuating salinity environments. However, to date, one of the core questions involved in these physiological processes, i.e., the regulation of salt-induced compatible solute biosynthesis, is still not well understood. Here, this issue was systematically investigated by employing the model freshwater cyanobacterium Synechococcus elongatus PCC 7942. A novel mechanism for cyanobacterial adaption to salt stress and fluctuating salinity, i.e., the ion-induced synergistic modulation of key synthesizing and degrading enzymes of compatible solutes, is proposed. Because the ion-induced activation/inhibition of enzymes is a fast and efficient process, it may represent a common strategy of microbes for adaptation to environments with fluctuating salinity.


Assuntos
Adaptação Fisiológica , Salinidade , Estresse Salino/fisiologia , Synechococcus/fisiologia
10.
Biomacromolecules ; 21(10): 4212-4219, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-32886490

RESUMO

The elegant elasticity and toughness of muscles that are controlled by myofilament sliding, highly elastic springlike properties of titin, and Ca2+-induced conformational change of the troponin complex have been a source of inspiration to develop advanced materials for simulating elastic muscle motion. Herein, a highly stretchable protein hydrogel is developed to mimic the structure and motion of muscles through the combination of protein folding-unfolding and molecular sliding. It has been shown that the protein bovine serum albumin is covalently cross-linked, together penetrated with alginate chains to construct polyprotein-based hydrogels, where polyproteins can act as the elastic spring titin via protein folding-unfolding and also achieve tunable sliding facilitated by alginate due to their reversible noncovalent interactions, thus providing desired mechanical properties such as stretchability, resilience, and strength. Notably, these biomaterials can achieve the breaking strain of up to 1200% and show massive energy dissipation. A pronounced expansion-contraction phenomenon is also observed on the macroscopic scale, and the Ca2+-induced contraction process may help to improve our understanding of muscle movement. Overall, these excellent properties are comparable to or even better than those of natural muscles, making the polyprotein-based hydrogels represent a new type of muscle-mimetic biomaterial. Significantly, the prominent biocompatibility of the designed biomaterials further enables them to hold potential applications in the biomedical field and tissue engineering.


Assuntos
Materiais Biocompatíveis , Hidrogéis , Animais , Bovinos , Elasticidade , Músculos , Engenharia Tecidual
11.
Macromol Rapid Commun ; 41(6): e1900586, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32022359

RESUMO

Orthogonal dynamic covalent self-assembly is used as a facile method for constructing polymer hollow nanocapsules (NCs) and thin films. The bifunctional precursor 4-formylphenylboronic acid is symmetrically installed with a boronic acid group for the boroxine linkage, and an aldehyde group for the Schiff base reaction which can react with twofold symmetry linkers ethylenediamine and para phenylenediamine to attain polymer NCs and nanosheets. Owing to the reversibility of the imine linkages, the mutual morphological transformation between polymer NCs and thin films via an amine-imine-exchange strategy is successfully achieved. Multiple reversible covalent bonds allow the control the release of the load in polymer NCs using different techniques. This may be useful for designing stimulus-responsive smart materials.


Assuntos
Benzaldeídos/química , Ácidos Borônicos/química , Etilenodiaminas/química , Iminas/química , Nanocápsulas/química , Fenilenodiaminas/química , Polímeros/química , Polímeros/síntese química , Aldeídos/química , Aminas/química , Nanocápsulas/ultraestrutura , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Bases de Schiff/química , Propriedades de Superfície
12.
Appl Microbiol Biotechnol ; 104(12): 5229-5241, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32342145

RESUMO

In bacteria, the truncated forms of mRNAs, which usually lack a stop codon, are occasionally generated by premature termination of gene transcription and/or endo- or exonucleolytic cleavage events. Ribosomes proceeding on these molecules stall at the 3' end of the chain and are rescued by a widely distributed mechanism known as trans-translation, which includes two essential elements, ssrA RNA (a special RNA) and SmpB (a small protein). Through this mechanism, the polypeptides translated from truncated mRNAs are marked by a short peptide, known as SsrA tag, at their C-termini and directed to the specific endogenous proteases for C-terminal proteolysis. Based on the deep understanding of the SsrA tagging and degradation mechanisms, recently a series of SsrA-based genetic tools have been developed for gene regulation on the level of post-translation. They are successfully applied for controllable regulation of biological circuits in bacteria. In the present article, we systematically summarize the history, structural characteristics, and functional mechanisms of the SsrA tagging and degrading machineries, as well as their technical uses and limitations.Key Points• SsrA system plays an important role in ribosome rescue in bacteria.• SsrA-based genetic tools are useful for controlling protein levels and activities.


Assuntos
Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , RNA Mensageiro/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Bactérias/genética , Biossíntese de Proteínas , Proteínas de Ligação a RNA/genética , Ribossomos/metabolismo
13.
Small ; 15(15): e1900350, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30891901

RESUMO

Enzyme as signal tag has been widely employed in colorimetric immunoassays for decades. Nevertheless, it remains a great challenge to substantially improve the detection sensitivity of enzyme-based immunoassays, which inhibits further critical applications. To circumvent this confinement, a multifunctional self-assembled proteinosome based on the integration of signal amplification elements (enzyme) and biorecognition unit (antibody) is proposed for fabricating an immunoassay strategy with significantly enhanced sensitivity. Owing to the self-assembly technique, this proteinosome not only efficiently loads abundant enzymes to possess high catalytic activity, but also enhances enzymatic stability and maintains recognition ability of antibody. Using imidacloprid as a model target, the proteinosome-based immunoassay reaches a limit of detection down to the picogram mL-1 level, which is 150-fold lower than that of conventional enzyme-linked immunosorbent assay. This method provides a versatile approach for constructing spherical proteinosome as a recognizer and amplifier for profiling a broad range of target antigen.


Assuntos
Anticorpos/metabolismo , Enzimas/metabolismo , Imunoensaio/métodos , Processamento de Sinais Assistido por Computador , Cetrimônio/química , Colorimetria , Ensaio de Imunoadsorção Enzimática , Fluorescência , Peroxidase do Rábano Silvestre/metabolismo , Humanos , Eletricidade Estática
14.
Chemistry ; 25(44): 10350-10358, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31069854

RESUMO

The establishment of new enzymatic function in an existing scaffold is a great challenge for protein engineers. In previous work, a highly efficient artificial selenoenzyme with controllable activity was constructed, based on a Ca2+ -responsive recoverin (Rn) protein. In this study, a design strategy combining docking, molecular dynamics, and MM-PBSA is presented, to predict the catalytically active site of glutathione peroxidase (GPx) on the allosteric domain of Rn. The energy contributions of the binding hot spot residues are evaluated further by energy decomposition analysis to determine the detailed substrate recognition mechanism of Rn, which provides clear guidance for artificial enzyme design for improved substrate binding (Michaelis-Menten constant, Km ).


Assuntos
Glutationa Peroxidase/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Compostos Organosselênicos/química , Recoverina/química , Sítio Alostérico , Catálise , Domínio Catalítico , Cristalização , Ligação de Hidrogênio , Mutação , Conformação Proteica , Recoverina/genética , Termodinâmica
15.
Eur Radiol ; 29(7): 3945-3954, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30859285

RESUMO

PURPOSE: To investigate whether tumor texture features derived from pretreatment with 18F-fluorodeoxyglucose positron emission tomography (FDG PET) can predict histological response or event-free survival (EFS) in patients with localized osteosarcoma of the extremities treated by neoadjuvant chemotherapy (NAC). METHODS: We retrospectively reviewed 35 patients with American Joint Committee on Cancer stage II extremity osteosarcoma treated with NAC and surgery. Primary tumor traditional parameters and texture features were measured for all 18F-FDG PET images prior to treatment. After surgery, histological responses to NAC were evaluated on the postsurgical specimens. A receiver operating characteristic curve (ROC) was constructed to evaluate the optimal predictive performance among the various indices. EFS was calculated using the Kaplan-Meier method and prognostic significance was assessed by Cox proportional hazards analysis. RESULTS: Pathologic examination revealed 16 (45.71%) good responders and 19 (54.29%) poor responders. Although both the texture features (least axis, dependence nonuniformity, run length nonuniformity, and size zone nonuniformity) and metabolic tumor volume (MTV) can predict tumor response of osteosarcoma to NAC, the traditional indicator MTV has the best performance according to ROC curve analysis (area under the curve = 0.918, p < 0.0001). In multivariate analysis, MTV (p < 0.0001), histological response (p = 0.0003), and texture feature of coarsenessNGTDM (neighboring gray tone difference matrix) (p = 0.005) were independently associated with EFS. CONCLUSIONS: Intratumoral heterogeneity of baseline 18F-FDG uptake measured by PET texture analysis can predict tumor response and EFS of patients with extremity osteosarcoma treated by NAC, but the conventional parameter MTV provides better predictive power and is a strong independent prognostic factor. KEY POINTS: • The baseline 18 F-FDG PET tumor texture features can predict tumor NAC response for patients with osteosarcoma. • Coarseness NGTDM is a new and independent prognostic factor for osteosarcoma. • MTV provides the best predictive power and is a strong independent prognostic factor for patients with osteosarcoma.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Osteossarcoma/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adolescente , Adulto , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Criança , China , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/patologia , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Compostos Radiofarmacêuticos/administração & dosagem , Estudos Retrospectivos , Imagem Corporal Total , Adulto Jovem
16.
Macromol Rapid Commun ; 40(9): e1800892, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30791167

RESUMO

The characteristics of chloroplasts harvesting solar energy and conducting energy transfer have inspired chemists to mimic similar processes. However, accurate manipulation to gain regularly displayed antenna chromophores in mimicking chloroplasts is a great challenge. Herein, a rational design is presented that combines orderly arranged chromophores with aggregation-induced emission (AIE) to develop artificial light-harvesting systems. Tetraphenyl ethylene (TPE) molecules, which exhibited strong AIE properties, are considered as building blocks to fabricate high emissive 2D nanosheets and nanovesicles, respectively. Furthermore, the well-aligned TPE molecules are also developed as donor chromophores in light-harvesting processes. After subsequent surface modification by porphyrin molecules as acceptor chromophores, an efficient light-harvesting system has been integrally constructed. This study demonstrates a novel strategy to utilize AIE feature to mimic chloroplasts process in nature.


Assuntos
Complexos de Proteínas Captadores de Luz/química , Luz , Nanoestruturas/química , Porfirinas/química
17.
Endocr Pract ; 25(3): 279-286, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30913016

RESUMO

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) expression on tumor tissue has been associated with favorable response to anti-programmed cell death-receptor 1/PD-L1 therapy in many human cancers. Studies have reported that PD-L1 is also expressed in thyroid cancer. The objective of this paper is to introduce the potential predictive and therapeutic values of PD-L1 in thyroid cancer. METHODS: A literature search was conducted in the PubMed database using the terms "PD-L1," "B7-H1," and "thyroid cancer." PD-L1 positivity was determined by immunohistochemical assay. RESULTS: The frequency of PD-L1 positivity in different studies ranged from 6.1 to 82.5% in papillary thyroid cancer (PTC) patients and 22.2 to 81.2% in anaplastic thyroid cancer (ATC) patients. PD-L1 positivity rate was higher in ATC than in PTC within the same studies, and its expression intensity was significantly higher in tumor tissue than in the corresponding nontumor thyroid tissues. Moreover, PD-L1 expression was positively associated with the aggressiveness and recurrence of thyroid cancers and negatively associated with the differentiation status and outcomes. PD-L1 checkpoint pathway blockade may emerge as a promising therapeutic target in the treatment of thyroid cancers. CONCLUSION: PD-L1 is a potential biomarker to predict the recurrence and prognosis of thyroid cancers. It is also a novel immunotherapy target for optimizing the management landscape of radioiodine-refractory and ATCs. ABBREVIATIONS: ATC = anaplastic thyroid cancer; DTC = differentiated thyroid cancer; IHC = immunohistochemical; OS = overall survival; PD-1 = programmed cell death-receptor 1; PD-L1 = programmed cell death-ligand 1; PD-L2 = programmed cell death-ligand 2; PTC = papillary thyroid cancer; TNM = tumor-node-metastasis; Treg = regulatory T cell.


Assuntos
Neoplasias da Glândula Tireoide , Antígeno B7-H1 , Biomarcadores Tumorais , Morte Celular , Humanos , Radioisótopos do Iodo , Recidiva Local de Neoplasia , Prognóstico
18.
Cell Mol Life Sci ; 75(19): 3569-3592, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30046841

RESUMO

Multicopper oxidases (MCOs) are a pervasive family of enzymes that oxidize a wide range of phenolic and nonphenolic aromatic substrates, concomitantly with the reduction of dioxygen to water. MCOs are usually divided into two functional classes: metalloxidases and laccases. Given their broad substrate specificity and eco-friendliness (molecular oxygen from air as is used as the final electron acceptor and they only release water as byproduct), laccases are regarded as promising biological green tools for an array of applications. Among these laccases, those of bacterial origin have attracted research attention because of their notable advantages, including broad substrate spectrum, wide pH range, high thermostability, and tolerance to alkaline environments. This review aims to summarize the significant research efforts on the properties, mechanisms and structures, laccase-mediator systems, genetic engineering, immobilization, and biotechnological applications of the bacteria-source laccases and laccase-like enzymes, which principally include Bacillus laccases, actinomycetic laccases and some other species of bacterial laccases. In addition, these enzymes may offer tremendous potential for environmental and industrial applications.


Assuntos
Bactérias/enzimologia , Bioengenharia/tendências , Química Verde/tendências , Indústrias/tendências , Lacase/fisiologia , Animais , Bactérias/genética , Bioengenharia/métodos , Microbiologia Ambiental , Química Verde/métodos , Humanos , Indústrias/métodos , Invenções/tendências , Lacase/genética
19.
Mediators Inflamm ; 2019: 9515346, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686988

RESUMO

BACKGROUND: Interleukin-37 (IL-37) acts as an inhibitor of innate and adaptive immunity. However, the exact role of IL-37 in the patients with acute coronary syndrome (ACS) remains to be elucidated. METHODS: Patients were classified into 4 groups: normal coronary artery (NCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). The circulating Treg, Th1, and Th17 frequencies were measured. The effect of IL-37 on stimulated peripheral blood mononuclear cells (PBMCs) and the influence of IL-37 on DCs were explored. In addition, the role of IL-37-treated tDCs on Treg cell expansion and the stability of these tDCs were also tested. RESULTS: Our results showed that the circulating Treg frequencies were decreased, while Th1 and Th17 frequencies were increased in ACS patients, and that IL-37 expanded Tregs but suppressed Th1 and Th17 cells in activated PBMCs derived from ACS patients. Of note, IL-37-treated human DCs obtained a tolerogenic phenotype, and such tDCs promoted expansion of Tregs and decreased the Th1 and Th17 populations when cocultured with CD4+ T cells. Interestingly, IL-37-treated DCs from patients with ACS are phenotypically and functionally comparable to IL-37-treated DCs from NCA patients, and tolerogenic properties of IL-37-treated DCs were highly stable. CONCLUSION: In conclusion, our results reveal a beneficial role of IL-37 in the patients with ACS and suggest that autologous IL-37-treated tDCs may be a novel therapeutic strategy for the patients with ACS.


Assuntos
Síndrome Coronariana Aguda/metabolismo , Interleucina-1/farmacologia , Angina Estável/metabolismo , Angina Instável/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Células Cultivadas , Citometria de Fluxo , Humanos , Interleucina-17/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo
20.
Arch Gynecol Obstet ; 300(2): 261-267, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31175401

RESUMO

OBJECTIVE: The vaginal microbiota may modulate susceptibility to Neisseria gonorrhea (NG) infections. The objective of this meta-analysis was to evaluate the association between these NG infections and the vaginal microbiota. METHOD: A systematic review and meta-analysis was conducted to investigate the correlation of vaginal microbiota and NG risk. Primary sources of the reviewed studies were from inception through December 2018. Vaginal mucosa microflora were dichotomized into high-Lactobacillus vaginal microbiota and low-Lactobacillus vaginal microbiota (LL-VMB), using either Nugent score, Amsel's criteria, presence of clue cells or 16S rRNA gene sequencing. RESULTS: A total of 8 studies qualified for inclusion in this meta-analysis. LL-VMB could be regarded as worse prognostic factor, and the pooled OR was 1.33 (95% CI 1.02, 1.73; P = 0.04, I2 = 44%). LL-VMB was associated with a significantly higher susceptibility of NG. Trend for the sensitive analysis was consistence with the primary outcome. Significant publication bias was not detected by the funnel plot. CONCLUSION: In conclusion, the systematic review and meta-analysis has demonstrated that LL-VMB was significantly associated with a high NG susceptibility.


Assuntos
Gonorreia/fisiopatologia , Mucosa/virologia , Neisseria gonorrhoeae/patogenicidade , Vagina/virologia , Feminino , Humanos , RNA Ribossômico 16S
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