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Cirratiomycin, a heptapeptide with antibacterial activity, was isolated and characterized in 1981; however, its biosynthetic pathway has not been elucidated. It contains several interesting nonproteinogenic amino acids, such as (2S,3S)-2,3-diaminobutyric acid ((2S,3S)-DABA) and α-(hydroxymethyl)serine, as building blocks. Here, we report the identification of a cirratiomycin biosynthetic gene cluster in Streptomyces cirratus. Bioinformatic analysis revealed that several Streptomyces viridifaciens and Kitasatospora aureofaciens strains also have this cluster. One S. viridifaciens strain was confirmed to produce cirratiomycin. The biosynthetic gene cluster was shown to be responsible for cirratiomycin biosynthesis in S. cirratus in a gene inactivation experiment using CRISPR-cBEST. Interestingly, this cluster encodes a nonribosomal peptide synthetase (NRPS) composed of 12 proteins, including those with an unusual domain organization: a stand-alone adenylation domain, two stand-alone condensation domains, two type II thioesterases, and two NRPS modules that have no adenylation domain. Using heterologous expression and inâ vitro analysis of recombinant enzymes, we revealed the biosynthetic pathway of (2S,3S)-DABA: (2S,3S)-DABA is synthesized from l-threonine by four enzymes, CirR, CirS, CirQ, and CirB. In addition, CirH, a glycine/serine hydroxymethyltransferase homolog, was shown to synthesize α-(hydroxymethyl)serine from d-serine inâ vitro. These findings broaden our knowledge of nonproteinogenic amino acid biosynthesis.
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Vias Biossintéticas , Família Multigênica , Serina , Streptomyces , Streptomyces/genética , Streptomyces/metabolismo , Serina/análogos & derivados , Serina/metabolismo , Serina/química , Serina/biossíntese , Peptídeo Sintases/metabolismo , Peptídeo Sintases/genética , Aminobutiratos/química , Aminobutiratos/metabolismo , Antibacterianos/biossíntese , Antibacterianos/químicaRESUMO
Distinguishing agents of bone modification at paleoanthropological sites is an important means of understanding early hominin evolution. Fracture pattern analysis is used to help determine site formation processes, including whether hominins were hunting or scavenging for animal food resources. Determination of how these behaviors manifested in ancient human sites has major implications for our biological and behavioral evolution, including social and cognitive abilities, dietary impacts of having access to in-bone nutrients like marrow, and cultural variation in butchering and food processing practices. Nevertheless, previous analyses remain inconclusive, often suffering from lack of replicability, misuse of mathematical methods, and/or failure to overcome equifinality. In this paper, we present a new approach aimed at distinguishing bone fragments resulting from hominin and carnivore breakage. Our analysis is founded on a large collection of scanned three-dimensional models of fragmentary bone broken by known agents, to which we apply state of the art machine learning algorithms. Our classification of fragments achieves an average mean accuracy of 77% across tests, thus demonstrating notable, but not overwhelming, success for distinguishing the agent of breakage. We note that, while previous research applying such algorithms has claimed higher success rates, fundamental errors in the application of machine learning protocols suggest that the reported accuracies are unjustified and unreliable. The systematic, fully documented, and proper application of machine learning algorithms leads to an inherent reproducibility of our study, and therefore our methods hold great potential for deciphering when and where hominins first began exploiting marrow and meat, and clarifying their importance and influence on human evolution.
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Carnívoros , Hominidae , Animais , Humanos , Reprodutibilidade dos Testes , Hominidae/psicologia , Osso e Ossos , Aprendizado de MáquinaRESUMO
The functional alterations of the brain in bipolar II depression (BDII-D) and their clinical and inflammatory associations are understudied. We aim to investigate the functional brain alterations in BDII-D and their relationships with inflammation, childhood adversity, and psychiatric symptoms, and to examine the moderating effects among these factors. Using z-normalized amplitude of low-frequency fluctuation (zALFF), we assessed the whole-brain resting-state functional activity between 147 BDII-D individuals and 150 healthy controls (HCs). Differential ALFF regions were selected as seeds for functional connectivity analysis to observe brain connectivity alterations resulting from abnormal regional activity. Four inflammatory cytokines including interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) and five clinical scales including Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Positive and Negative Syndrome Scale (PANSS), Columbia-Suicide Severity Rating Scale (C-SSRS), and Childhood Trauma Questionnaire (CTQ) were tested and assessed in BDII-D. Partial correlations with multiple comparison corrections identified relationships between brain function and inflammation, childhood adversity, and psychiatric symptoms. Moderation analysis was conducted based on correlation results and previous findings. Compared to HCs, BDII-D individuals displayed significantly lower zALFF in the superior and middle frontal gyri (SFG and MFG) and insula, but higher zALFF in the occipital-temporal area. Only the MFG and insula-related connectivity exhibited significant differences between groups. Within BDII-D, lower right insula zALFF value correlated with higher IL-6, CRP, and emotional adversity scores, while lower right MFG zALFF was related to higher CRP and physical abuse scores. Higher right MFG-mid-anterior cingulate cortex (mACC) connectivity was associated with higher IL-1ß. Moreover, IL-1ß moderated associations between higher right MFG-mACC/insula connectivity and greater depressive symptoms. This study reveals that abnormal functional alterations in the right MFG and right insula were associated with elevated inflammation, childhood adversity, and depressive symptoms in BDII-D. IL-1ß may moderate the relationship between MFG-related connectivity and depressive symptoms.
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Transtorno Bipolar , Depressão , Interleucina-1beta , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Transtorno Bipolar/metabolismo , Transtorno Bipolar/fisiopatologia , Adulto , Interleucina-1beta/metabolismo , Depressão/metabolismo , Depressão/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Inflamação/metabolismo , Córtex Insular/metabolismo , Pessoa de Meia-Idade , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Escalas de Graduação Psiquiátrica , Experiências Adversas da Infância , Vias Neurais/fisiopatologia , Vias Neurais/metabolismo , Mapeamento Encefálico/métodos , Adulto Jovem , Lobo Frontal/metabolismo , Lobo Frontal/fisiopatologiaRESUMO
Bioleaching of lithium-ion batteries is a microbially catalyzed process. Under the action of redox, acid leaching and complexation in the presence of microorganisms, the valuable metals in the cathode material enter the liquid phase as ions and are subsequently recovered from the succeeding process. This technique has the advantages of being inexpensive, environmentally friendly and having simple needs. However, it is still in development and has not yet commercialized. In this paper, the technology is fully discussed based on numerous excellent studies. The contents include commonly utilized microorganisms, bioleaching mechanism, microbial stress response and metabolic activation, enhancement strategies, leaching characteristics and interfacial phenomena, process evaluation, and a critical discussion of recent research breakthroughs. They give readers with comprehensive and in-depth understanding on the bioleaching of lithium-ion batteries and help to improve the technology's industrialization. Researchers can make new explorations from the potential research directions and methods presented in this work to make biotechnology better serve resource recovery and social development.
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Lítio , Reciclagem , Metais , Fontes de Energia Elétrica , Íons , BiotecnologiaRESUMO
Random skin flap grafting is the most common skin grafting technique in reconstructive surgery. Despite progress in techniques, the incidence of distal flap necrosis still exceeds 3%, which limits its use in clinical practice. Current methods for treating distal flap necrosis are still lacking. Pinocembrin (Pino) can inhibit reactive oxygen species (ROS) and cell death in a variety of diseases, such as cardiovascular diseases, but the role of Pino in random flaps has not been explored. Therefore, we explore how Pino can enhance flap survival and its specific upstream mechanisms via macroscopic examination, Doppler, immunohistochemistry, and western blot. The results suggested that Pino can enhance the viability of random flaps by inhibiting ROS, pyroptosis and apoptosis. The above effects were reversed by co-administration of Pino with adeno-associated virus-silencing information regulator 2 homolog 3 (SIRT3) shRNA, proving the beneficial effect of Pino on the flaps relied on SIRT3. In addition, we also found that Pino up-regulates SIRT3 expression by activating the AMP-activated protein kinase (AMPK) pathway. This study proved that Pino can improve random flap viability by eliminating ROS, and ROS-induced cell death through the activation of SIRT3, which are triggered by the AMPK/PGC-1α signaling pathway.
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Piroptose , Sirtuína 3 , Humanos , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Sirtuína 3/metabolismo , Apoptose , NecroseRESUMO
This paper designs a fast image-based indoor localization method based on an anchor control network (FILNet) to improve localization accuracy and shorten the duration of feature matching. Particularly, two stages are developed for the proposed algorithm. The offline stage is to construct an anchor feature fingerprint database based on the concept of an anchor control network. This introduces detailed surveys to infer anchor features according to the information of control anchors using the visual-inertial odometry (VIO) based on Google ARcore. In addition, an affine invariance enhancement algorithm based on feature multi-angle screening and supplementation is developed to solve the image perspective transformation problem and complete the feature fingerprint database construction. In the online stage, a fast spatial indexing approach is adopted to improve the feature matching speed by searching for active anchors and matching only anchor features around the active anchors. Further, to improve the correct matching rate, a homography matrix filter model is used to verify the correctness of feature matching, and the correct matching points are selected. Extensive experiments in real-world scenarios are performed to evaluate the proposed FILNet. The experimental results show that in terms of affine invariance, compared with the initial local features, FILNet significantly improves the recall of feature matching from 26% to 57% when the angular deviation is less than 60 degrees. In the image feature matching stage, compared with the initial K-D tree algorithm, FILNet significantly improves the efficiency of feature matching, and the average time of the test image dataset is reduced from 30.3 ms to 12.7 ms. In terms of localization accuracy, compared with the benchmark method based on image localization, FILNet significantly improves the localization accuracy, and the percentage of images with a localization error of less than 0.1m increases from 31.61% to 55.89%.
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Random-pattern skin flaps are widely applied to rebuild and restore soft-tissue damage in reconstructive surgery; however, ischemia and subsequent ischemia-reperfusion injury lead to flap necrosis and are major complications. Exenatide, a glucagon-like peptide-1 analog, exerts therapeutic benefits for diabetic wounds, cardiac injury, and nonalcoholic fatty liver disease. Furthermore, Exenatide is a known activator of autophagy, which is a complex process of subcellular degradation that may enhance the viability of random skin flaps. In this study, we explored whether exenatide can improve skin flap survival. Our results showed that exenatide augments autophagy, increases flap viability, enhances angiogenesis, reduces oxidative stress, and alleviates pyroptosis. Coadministration of exenatide with 3-methyladenine and chloroquine, potent inhibitors of autophagy, reversed the beneficial effects, suggesting that the therapeutic benefits of exenatide for skin flaps are due largely to autophagy activation. Mechanistically, we identified that exenatide enhanced activation and nuclear translocation of TFE3, which leads to autophagy activation. Furthermore, we found that exenatide activates the AMPK-SKP2-CARM1 and AMPK-mTOR signaling pathways, which likely lead to exenatide's effects on activating TFE3. Overall, our findings suggest that exenatide may be a potent therapy to prevent flap necrosis, and we also reveal novel mechanistic insight into exenatide's effect on flap survival.
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Exenatida/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Pele , Pele/irrigação sanguínea , Adenina/análogos & derivados , Adenina/farmacologia , Adenilato Quinase/metabolismo , Animais , Autofagia/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Regulação para Baixo/efeitos dos fármacos , Edema/patologia , Masculino , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Proteína-Arginina N-Metiltransferases/metabolismo , Piroptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
The specific identification and elimination of cancer cells has been a great challenge in the past few decades. In this study, the circular dichroism (CD) of cells was measured by a self-designed special system through the folate-conjugated chiral nano-sensor. A novel method was established to recognize cancer cells from normal cells according to the chirality of cells based on their CD signals. After a period of interaction between the nano-sensor and cells, the sharp weakening of CD signals was induced in cancer cells but normal cells remained unchanged. The biocompatibility of the nano-sensor was evaluated and the result showed that it exhibited significant cytotoxic activity against cancer cells while no obvious damage on normal cells. Notably, the research indicated that the nano-sensor may selectively cause apoptosis in cancer cells, and thus, have the potential to act as an antitumor agent.
Assuntos
Compostos de Cádmio , Neoplasias/terapia , Pontos Quânticos/química , Sulfetos , Telúrio , Apoptose , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Dicroísmo Circular , Feminino , Ácido Fólico , HumanosRESUMO
Trichome initiation and leaf growth are two critical developmental processes in the plant life cycle, which need to be optimized in accordance with developmental stage and immediate surroundings. To a large extent, this optimization is achieved by fine-tuning of hormonal pathways, including the gibberellin (GA) pathway. However, the mechanism by which plants control GA homeostasis to optimize these two developmental processes is unknown. Here, we report that HAT1, a HD-ZIP II transcription factor, negatively regulates GA-mediated trichome initiation and cotyledon expansion. Both protein and transcript levels indicated that HAT1 was induced by GA, while an increased abundance of HAT1, in turn, was found to suppress GA biosynthesis and signaling, thus forming a regulatory negative feedback loop that controls GA homeostasis to fine-tune trichome development and cotyledon expansion. We also found that HAT1 interacts with DELLAs, including GAI and RGA. GAI inhibits both protein stability and the binding activity of HAT1 to its target genes. Overexpression of HAT1 in della5 can completely suppress the enhanced trichome initiation and enlarged cotyledon of della5. Our findings demonstrate that HAT1 functions as a critical repressor to regulate GA-mediated trichome initiation and cotyledon growth; in addition, we describe a novel mechanism by which the plant regulates trichome initiation and cotyledon expansion through a HAT1-DELLA regulatory module under various GA concentrations.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Giberelinas , Histona Acetiltransferases , Homeostase , Folhas de Planta/metabolismo , Fatores de Transcrição , Tricomas/metabolismoRESUMO
In the original publication the section heading "Classification of microorganisms" appearing above the sub-section "Air and liquid circulation in the heap" in page four is incorrect. The correct section heading should be read as "Results and discussion".
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Heap biooxidation method was used to evaluate the availability of Paodaoling gold ore in Anhui province, China. 15,000 tons of gold ores (≤ 10 mm in diameter) were bioxidized under mesophilic conditions. Under the synergistic effect of microbial community, arsenic and sulfur were oxidized by 42% and 38% after 80 days. Relatively, leaching of gold was improved from 36 to 78% after heap biooxidation. The sequencing results showed there were 28 operational taxonomic units identified the microbial community in the heap. The main genera were Acidithiobacillus, Ferroplasma, Acidiferrobacter and Nitrospira. According to stoichiometry, the content of microorganisms with various functions tended to be balanced. The biomass production rate was 10 g/s, the CO2 fixation rate was 18 g/s, and the oxygen consumption rate was 60 g/s. This study provides a good basis for the further design and application of heap biooxidation technology.
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Bactérias , Acidithiobacillus , Arsênio , China , Ouro , OxirreduçãoRESUMO
PURPOSE: Data from in vitro and animal studies support the preventive effect of tea (Camellia sinensis) against colorectal cancer. Further, many epidemiologic studies evaluated the association between tea consumption and colorectal cancer risk, but the results were inconsistent. We conducted a meta-analysis of prospective cohort studies to systematically assess the association between tea consumption and colorectal cancer risk. METHODS: A comprehensive literature review was conducted to identify the related articles by searching PubMed and Embase up to June, 2019. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a fixed effect model. RESULTS: Twenty cohort articles were included in the present meta-analysis involving 2,068,137 participants and 21,437 cases. The combined RR of colorectal cancer for the highest vs. lowest tea consumption was determined to 0.97 (95% CI 0.94-1.01) with marginal heterogeneity (I2 = 24.0%, P = 0.093) among all studies. This indicated that tea consumption had no significant association with colorectal cancer risk. Stratified analysis showed that no significant differences were found in all subgroups. We further conducted the gender-specific meta-analysis for deriving a more precise estimation. No significant association was observed between tea consumption and colorectal cancer risk in male (combined RR = 0.97; 95% CI 0.90-1.04). However, tea consumption had a marginal significant inverse impact on colorectal cancer risk in female (combined RR = 0.93; 95% CI 0.86-1.00). Further, we found a stronger inverse association between tea consumption and risk of colorectal cancer among the female studies with no adjustment of coffee intake (RR: 0.90; 95% CI 0.82-1.00, P < 0.05) compared to the female studies that adjusted for coffee intake (RR = 0.97; 95% CI 0.87-1.09, P > 0.05). CONCLUSIONS: Our finding indicates that tea consumption has no significant impact on the colorectal cancer risk in both genders combined, but gender-specific meta-analysis shows that tea consumption has a marginal significant inverse impact on colorectal cancer risk in female.
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Neoplasias Colorretais , Chá , Café , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Feminino , Humanos , Masculino , Estudos Prospectivos , Risco , Fatores de RiscoRESUMO
BACKGROUND: Intercropping and close planting are important cultivation methods that increase soybean yield in agricultural production. However, plant shading is a major abiotic stress factor that influences soybean growth and development. Although shade affects leaf morphological parameters and decreases leaf photosynthesis capacity, information on the responses of soybean leaf photosynthesis to shading at proteomic level is still lacking. RESULTS: Compared with leaves under normal light (CK) treatment, leaves under shading treatment exhibited decreased palisade and spongy tissue thicknesses but significantly increased cell gap. Although shade increased the number of the chloroplast, the thickness of the grana lamella and the photosynthetic pigments per unit mass, but the size of the chloroplast and starch grains and the rate of net photosynthesis decreased compared with those of under CK treatment. A total of 248 differentially expressed proteins, among which 138 were upregulated, and 110 were downregulated, in soybean leaves under shading and CK treatments were detected via isobaric tags for relative and absolute quantification labeling in the three biological repeats. Differentially expressed proteins were classified into 3 large and 20 small groups. Most proteins involved in porphyrin and chlorophyll metabolism, photosynthesis-antenna proteins and carbon fixation in photosynthetic organisms were upregulated. By contrast, proteins involved in photosynthesis were downregulated. The gene family members corresponding to differentially expressed proteins, including protochlorophyllide reductase (Glyma06g247100), geranylgeranyl hydrogenase (Ggh), LHCB1 (Lhcb1) and ferredoxin (N/A) involved in the porphyrin and chlorophyll metabolism, photosynthesis-antenna proteins and photosynthesis pathway were verified with real-time qPCR. The results showed that the expression patterns of the genes were consistent with the expression patterns of the corresponding proteins. CONCLUSIONS: This study combined the variation of the soybean leaf structure and differentially expressed proteins of soybean leaves under shading. These results demonstrated that shade condition increased the light capture efficiency of photosystem II (PSII) in soybean leaves but decreased the capacity from PSII transmitted to photosystem II (PSI). This maybe the major reason that the photosynthetic capacity was decreased in shading.
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Glycine max/metabolismo , Folhas de Planta/metabolismo , Proteômica/métodos , Plântula/metabolismo , Luz , Fotossíntese/genética , Fotossíntese/fisiologia , Complexo de Proteína do Fotossistema II/metabolismo , Folhas de Planta/genética , Folhas de Planta/efeitos da radiação , Plântula/genética , Plântula/efeitos da radiação , Glycine max/genética , Glycine max/efeitos da radiaçãoRESUMO
Semimetal 1T' MoTe2 crystals have attracted tremendous attention owing to their anisotropic optical properties, Weyl semimetal, phase transition, and so on. However, the complex refractive indices (n-ik) of the anisotropic semimetal 1T' MoTe2 still are not revealed yet, which is important to applications such as polarized wide spectrum detectors, polarized surface plasmonics, and nonlinear optics. Here, the linear dichroism of as-grown trilayer 1T' MoTe2 single crystals is investigated. Trilayer 1T' MoTe2 shows obvious anisotropic optical absorption due to the intraband transition of dz 2 orbits for Mo atoms and px orbits for Te atoms. The anisotropic complex refractive indices of few-layer 1T' MoTe2 are experimentally obtained for the first time by using the Pinier equation analysis. Based on the linear dichroism of 1T' MoTe2 , angle-resolved polarized optical microscopy is developed to visualize the grain boundary and identify the crystal orientation of 1T' MoTe2 crystals, which is also an excellent tool toward the investigation of the optical absorption properties in the visible range for anisotropic 2D transition metal chalcogenides. This work provides a universal and nondestructive method to identify the crystal orientation of anisotropic 2D materials, which opens up an opportunity to investigate the optical application of anisotropic semimetal 2D materials.
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BACKGROUND: Hyperthermia has proved successful in treating cutaneous human papillomavirus infectious diseases such as plantar wart and condyloma acuminata (CA). Moreover, this treatment provides improved therapeutic efficacy in these conditions as compared with conventional therapies. OBJECTIVES: To investigate the global proteome changes in CA in response to hyperthermia and achieve a better understanding of the mechanisms of hyperthermia therapy against HPV-infectious diseases. METHODS: CA tissue was obtained from patients undergoing pathological examinations. Diagnosis was verified as based on results of both HE staining and HPV-DNA PCR assay. Hyperthermia was achieved with a 44 °C water bath. Differentially expressed proteins (DEPs) were identified by iTRAQ labeling, SCX chromatography and LC-MS/MS assay. Validation of proteomic results was performed using real-time qPCR and western blot, while bioinformatic analysis of DEPs was accomplished by R 3.4.1, STRING and Cytoscape softwares. RESULTS: In response to hyperthermia, a total of 102 DEPs were identified with 37 being upregulated and 65 downregulated. Among these DEPs, hyperthermia induced proteins involved with anti-viral processes such as OAS1, MX1, BANF1, CANX and AP1S1, whereas it inhibited proteins that participated in cellular metabolism, such as GALT, H6PD, EXOSC4 and EXOSC6; protein translation, such as RPS4Y1; as well as keratinocyte differentiation, such as KRT5, KRT27, KRT75, KRT76 and H2AFY2. CONCLUSIONS: Hyperthermia inhibited enzymes and molecules responsible for metabolism modulation and keratinocyte differentiation in CA tissue, whereas it promoted factors involved in anti-viral responses. Such effects may, in part, contribute to the efficacy of local hyperthermia therapy against HPV infection.
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Biologia Computacional/métodos , Condiloma Acuminado/fisiopatologia , Hipertermia Induzida/métodos , Queratinócitos/patologia , Infecções por Papillomavirus/complicações , Proteômica/métodos , Diferenciação Celular , Feminino , Humanos , MasculinoRESUMO
The iridoids of Hedyotis diffusa Willd play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism has not be thoroughly studied. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Its anti-inflammatory mechanism was confirmed by in intro experiments and molecular docking analyses. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 messenger RNA (mRNA) expression in LPS-induced RAW 264.7 macrophages. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development.
Assuntos
Anti-Inflamatórios/farmacologia , Hedyotis/química , Iridoides/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/antagonistas & inibidores , Dinoprostona/biossíntese , Quinase I-kappa B/antagonistas & inibidores , Quinase I-kappa B/química , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Iridoides/química , Iridoides/isolamento & purificação , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Simulação de Acoplamento Molecular , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/química , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Overexpression of the nucleoporin NUP88 has been observed in a large number of tumors and has been experimentally proven to promote tumorigenesis. However, the mechanism underlying the tumor-promoting activity of overexpressed NUP88 is not clear. To investigate the potential pathways that drive tumorigenesis under NUP88 overexpressed condition, we applied a proteomic approach to identify NUP88-associated proteins at a subcellular compartment level. Gene ontology analysis revealed significant associations between NUP88 interactome and biological processes that are related to nuclear transport, RNA processing, cell cycle progression, metabolic regulation, and viral infection. Moreover, we found that NUP88 interacts with MISP, a mitotic interactor and substrate of PLK1. Interestingly, NUP88 overexpression blocks MISP phosphorylation, which is known to be critical for normal spindle formation and accurate chromosome segregation during mitosis. In conclusion, our data for the first time provide a global view of biological processes that may drive tumorigenesis under NUP88 overexpressed condition, revealing a biological effect of NUP88-MISP interaction. Furthermore, identification of NUP88-associated proteins provides a valuable database for future studies. © 2016 Wiley Periodicals, Inc.
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Biomarcadores Tumorais/metabolismo , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Proteoma/análise , Proteômica/métodos , Apoptose , Western Blotting , Proliferação de Células , Células HeLa , Humanos , Imunoprecipitação , Células MCF-7 , Complexo de Proteínas Formadoras de Poros Nucleares/genéticaRESUMO
Metastasis is a serious risk that may occur during the treatment of hepatocellular carcinoma (HCC), preventing many patients from being surgical candidates and contributing to poor prognosis. Hypoxia has been proved an important factor of metastasis through the epithelial-mesenchymal transition (EMT) pathway. Acetyl-CoA synthase 2 (ACSS2) provides an acetyl group for the acetylation of hypoxia-inducible factor (HIF)-2α, and this epigenetic modification affects the activity of HIF-2α and the subsequent EMT process. Here, we showed that ACSS2 expression was negatively correlated with HCC malignancy. Knockdown of ACSS2 increased the invasion and migration ability of HCC cells and promoted EMT without increasing the total protein level of HIF-2α, even in hypoxic conditions. The immunoprecipitation assay revealed downregulated acetylation levels of HIF-2α after ACSS2 knockdown in hypoxic conditions, which resulted in enhanced HIF-2α activity. Finally, decreased expression of ACSS2 was found to be related to advanced stage and poor overall survival and disease-free survival rates in a cohort of patients with HCC. In conclusion, ACSS2 plays an important role in the acetylation process of HIF-2α, which effectively modifies the activity of HIF-2α under hypoxic conditions and greatly impacts on the prognosis of patients with HCC.
Assuntos
Acetato-CoA Ligase/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Acetilação , Western Blotting , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Humanos , Imuno-Histoquímica , Imunoprecipitação , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Prognóstico , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Although many content-based image retrieval systems have been developed, few studies have focused on hyperspectral remote sensing images. In this paper, a hyperspectral remote sensing image retrieval system based on spectral and texture features is proposed. The main contributions are fourfold: (1) considering the "mixed pixel" in the hyperspectral image, endmembers as spectral features are extracted by an improved automatic pixel purity index algorithm, then the texture features are extracted with the gray level co-occurrence matrix; (2) similarity measurement is designed for the hyperspectral remote sensing image retrieval system, in which the similarity of spectral features is measured with the spectral information divergence and spectral angle match mixed measurement and in which the similarity of textural features is measured with Euclidean distance; (3) considering the limited ability of the human visual system, the retrieval results are returned after synthesizing true color images based on the hyperspectral image characteristics; (4) the retrieval results are optimized by adjusting the feature weights of similarity measurements according to the user's relevance feedback. The experimental results on NASA data sets can show that our system can achieve comparable superior retrieval performance to existing hyperspectral analysis schemes.
RESUMO
Image dehazing has received extensive research attention as images collected in hazy weather are limited by low visibility and information dropout. Recently, disentangled representation learning has made excellent progress in various vision tasks. However, existing networks for low-level vision tasks lack efficient feature interaction and delivery mechanisms in the disentanglement process or an evaluation mechanism for the degree of decoupling in the reconstruction process, rendering direct application to image dehazing challenging. We propose a self-guided disentangled representation learning (SGDRL) algorithm with a self-guided disentangled network to realize multi-level progressive feature decoupling through sharing and interaction. The self-guided disentangled (SGD) network extracts image features using the multi-layer backbone network, and attribute features are weighted using the self-guided attention mechanism for the backbone features. In addition, we introduce a disentanglement-guided (DG) module to evaluate the degree of feature decomposition and guide the feature fusion process in the reconstruction stage. Accordingly, we develop SGDRL-based unsupervised and semi-supervised single image dehazing networks. Extensive experiments demonstrate the superiority of the proposed method for real-world image dehazing. The source code is available at https://github.com/dehazing/SGDRL.