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1.
Trends Pharmacol Sci ; 40(11): 883-896, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31677920

RESUMO

B7x (B7 homolog x, also known as B7-H4, B7S1, and VTCN1) was discovered by ourselves and others in 2003 as the seventh member of the B7 family. It is an inhibitory immune checkpoint of great significance to human disease. Tissue-expressed B7x minimizes autoimmune and inflammatory responses. It is overexpressed in a broad spectrum of human cancers, where it suppresses antitumor immunity. Further, B7x and PD-L1 tend to have mutually exclusive expression in cancer cells. Therapeutics targeting B7x are effective in animal models of cancers and autoimmune disorders, and early-phase clinical trials are underway to determine the efficacy and safety of targeting B7x in human diseases. It took 15 years moving from the discovery of B7x to clinical trials. Further studies will be necessary to identify its receptors, reveal its physiological functions in organs, and combine therapies targeting B7x with other treatments.

2.
Adv Exp Med Biol ; 1172: 63-78, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31628651

RESUMO

The co-stimulation and co-inhibition signal pathways, immune checkpoints, are among the central mechanisms to regulate the T-cell immunity. Optimal signals involve intricate interactions of numerous ligands and receptors. Manipulation of these signals offers great clinical opportunities and has revolutionized the cancer treatment therapies. The 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo in recognition of their discovery of cancer immunotherapy by inhibition of immune checkpoint molecules. Despite the landmark discovery in cancer immunotherapy, the efforts to harness immunity against cancer are also restricted by the limited knowledge on the co-stimulation and co-inhibition signaling networks. Understanding the structures of these molecules, in particular, tackling the interaction paradigms from the structural perspective, help to provide more accurate insights into the signaling mechanisms, which may further facilitate the development of novel biologics and improve the efficacy of the existing biologics against these targets. Here we review our current understanding on the structures of these co-stimulatory and co-inhibitory molecules. Specifically, we focus on the structural basis of several checkpoint molecules among the CD28-B7 family and discuss the therapeutic drugs against these targets for the treatment of human cancers, autoimmune disorders, and transplantation.


Assuntos
Antígenos CD28 , Linfócitos T , Doenças Autoimunes , Antígenos CD28/química , Antígenos CD28/imunologia , Humanos , Imunoterapia , Neoplasias/terapia , Transplante de Órgãos , Transdução de Sinais/imunologia , Linfócitos T/imunologia
3.
Int J Biol Macromol ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31655154

RESUMO

High performance poly(vinyl alcohol) (PVA)/lignin nanomicelle (LNM) nanocomposite films with good vapor barrier and advanced UV-shielding properties were fabricated in this study. LNM was homogeneously distributed in the PVA matrix and strong robust hydrogen bonds were successfully constructed between LNM and PVA matrix. With only 5 wt% loading of LNM into the PVA/LNM nanocomposite, the water vapor transmission rate (WVTR) was declined by about 189% compared with pure PVA. Moreover, after introducing lignin, the PVA nanocomposite films showed improved tensile strength and toughness, excellent UV-blocking and good thermal stability. As both lignin and PVA are biodegradable, this study shows a meaningful design approach for biodegradable functional nanocomposite films using cheap and easily available biomass and biodegradable raw materials.

4.
Microb Cell Fact ; 18(1): 180, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31647018

RESUMO

BACKGROUND: Structurally stable α-galactosidases are of great interest for various biotechnological applications. More thermophilic α-galactosidases with high activity and structural stability have therefore to be mined and characterized. On the other hand, few studies have been performed to prominently enhance the AOX1 promoter activity in the commonly used Pichia pastoris system, in which production of some heterologous proteins are insufficient for further study. RESULTS: ReGal2 encoding a thermoactive α-galactosidase was identified from the thermophilic (hemi)cellulolytic fungus Rasamsonia emersonii. Significantly increased production of ReGal2 was achieved when ReGal2 was expressed in an engineered Pastoris pichia expression system with a modified AOX1 promoter and simultaneous fortified expression of Mxr1 that is involved in transcriptionally activating AOX1. Purified ReGal2 exists as an oligomer and has remarkable thermo-activity and thermo-tolerance, exhibiting maximum activity of 935 U/mg towards pNPGal at 80 °C and retaining full activity after incubation at 70 °C for 60 h. ReGal2 is insensitive to treatments by many metal ions and exhibits superior tolerance to protein denaturants. Moreover, ReGal2 efficiently hydrolyzed stachyose and raffinose in soybeans at 70 °C in 3 h and 24 h, respectively. CONCLUSION: A modified P. pichia expression system with significantly enhanced AOX1 promoter activity has been established, in which ReGal2 production is markedly elevated to facilitate downstream purification and characterization. Purified ReGal2 exhibited prominent features in thermostability, catalytic activity, and resistance to protein denaturants. ReGal2 thus holds great potential in relevant biotechnological applications.

5.
Water Sci Technol ; 80(2): 365-376, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31537773

RESUMO

At different calcination conditions, titanium-based manganese oxides (MnOx) electrodes were fabricated by spraying method without adhesive. The MnOx/Ti electrodes were applied in electrochemical oxidation of wastewater treatment for the first time. The surface morphologies of electrodes were tested by scanning electron microscopy. The formation of different manganese oxidation states on electrodes was confirmed by X-ray diffraction and X-ray photoelectron spectroscopy. The electrochemical properties of the electrodes have been performed by means of cyclic voltammetry and electrochemical impedance spectroscopy. The characterizations revealed that the MnOx/Ti-350(20) electrode, prepared at calcination temperature of 350 °C for 20 min, exhibited fewer cracks on the electrode surface, larger electrochemically effective surface area and lower charge transfer resistance than electrodes prepared at other calcination conditions. Moreover, Acid Red B was used as target pollutant to test the electrode activity via monitoring the concentration changes by UV spectrophotometer. The results showed that the MnOx/Ti-350(20) electrode presented the best performance on decolorization of Acid Red B with the lowest cell potential during the process of electrochemical oxidation, and the chemical oxygen demand (COD) conversion was 50.7%. Furthermore, the changes of Acid Red B during the electrochemical oxidation process were proposed by the UV-vis spectra.


Assuntos
Compostos Azo/química , Técnicas Eletroquímicas , Eletrodos , Naftalenossulfonatos/química , Poluentes Químicos da Água/química , Oxirredução , Titânio
6.
Cytokine ; 125: 154854, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31539844

RESUMO

BACKGROUND: Sepsis is a major cause of death for ICU patients. Sepsis development depends heavily on the presence of mature IL-1ß cytokine. This study evaluates the potential therapeutic properties of a bioactive compound known as 6-gingerol on sepsis. This compound has previously been demonstrated to possess anti-inflammatory properties both in vivo and in vitro. METHODS: C57BL/6 mice was used to establish models of sepsis by means of cecal ligation and puncture (CLP). Upon treatment with 6-gingerol, we assessed the survival rate of mice and measured the levels of key pro-inflammatory cytokines in serum and colon tissues. Sepsis pathogenesis was further explored using the RAW264.7 cell line and bone marrow-derived macrophages (BMDMs) treated with ATP and lipopolysaccharide (LPS). The impact of 6-gingerol on pyroptosis was also examined. In addition, we assessed the role of MAPK signaling in 6-gingerol-induced effects in BMDMs and RAW264.7 cells. RESULTS: In CLP mice, 6-gingerol significantly ameliorated sepsis development, which was associated with the reduction of serum IL-1ß. In BMDMs and RAW264.7 cells, 6-gingerol strongly attenuated pyroptosis as well as the release of caspase-1p20, HMGB1, mature IL-1ß, IL-18 in response to ATP and LPS treatment. 6-Gingerol conferred these effects by blocking MAPK activation. Exposure to an ERK agonist (EGF) reversed effects of 6-gingerol, causing pyroptosis, LDH and caspase-1p20 release. CONCLUSIONS: By targeting MAPK signaling, 6-gingerol significantly suppressed secretion of pro-inflammatory cytokines and inhibited macrophage cells pyroptosis resulting in overall inhibition of sepsis development.

7.
Immunology ; 158(4): 362-374, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31559637

RESUMO

The neuroinflammation following traumatic spinal cord injury (SCI) is a critical process that impacts both the injury and the recovery of spinal cord parenchyma. Infiltrating regulatory T (Treg) cells are potent anti-inflammatory cells that restrain post-SCI neuroinflammation. To understand the molecular mechanisms underlying the activity of infiltrating Treg cells, we used a mouse spinal cord compression injury model to analyze the role of Sirtuins (SIRTs) in the modulation of infiltrating Treg cell functions. We found that the expressions of SIRT4 and SIRT6 were up-regulated in infiltrating Treg cells. Using lentivirus-mediated gene expression or RNA interference, we revealed that SIRT4 substantially inhibited the expression of Foxp3, interleukin-10, and transforming growth factor-ß in Treg cells, whereas SIRT6 had little effect on Treg cells. Consistently, SIRT4 overexpression weakened the suppressive effect of Treg cells on lipopolysaccharide-stimulated spinal cord CD11b+ myeloid cells. Knock-down of SIRT4 enhanced the anti-inflammatory activity of infiltrating Treg cells in the parenchyma of injured spinal cords. Additionally, SIRT4 overexpression blocked in vitro Treg cell generation from conventional T cells. Furthermore, SIRT4 down-regulated 5' AMP-activated protein kinase (AMPK) signaling in Treg cells, whereas the AMPK agonist AICAR restored the expression of Foxp3 and interleukin-10 in SIRT4-overexpressing Treg cells. In conclusion, our research unveils a new mechanism by which the post-SCI neuroinflammation is regulated.

8.
Synapse ; 73(12): e22125, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31381191

RESUMO

Neuropathic pain is caused by somatosensory nervous system disorder which happens in patients with different diseases. Akt3 regulates innate immune function and plays a role in neuropathic pain pathogenesis in rats. MiR-20b-5p is a microRNA which has been suggested to inhibit Akt3 expression through directly targeting Akt3 mRNA. This research focused on miR-20b-5p function in neuropathic pain by Akt3 expression inhibition. Chronic constriction injury (CCI) was employed to induce neuropathic pain in rats. Paw withdrawal thresholds and paw withdrawal latency were examined to show neuropathic pain development. Expression levels of relative genes or microRNA were checked using qRT-PCR and western blot. Inflammation cytokine levels were measured by enzyme-linked immunosorbent assay kits. In CCI rat model, miR-20b-5p level was declined and Akt3 mRNA level was upregulated. MiR-20b-5p mimics suppressed the enhanced neuropathic pain, neuroinflammation, and Akt3 expression. MiR-20b-5p directly targeted Akt3 mRNA and downregulated the Akt3 expression in rat primary microglial cells. MiR-20b-5p inhibitory function in neuropathic pain was suppressed by the upregulation of Akt3 expression. This research illustrated that miR-20b-5p alleviated neuropathic pain through the inhibition of Akt3 expression in CCI rat model.

9.
Biotechnol Bioeng ; 116(11): 3030-3040, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31403179

RESUMO

Trichoderma spp. are main producers of peptide antibiotics known as peptaibols. While peptaibols have been shown to possess a range of biological activities, molecular understanding of the regulation of their production is largely unclear, which hampers the production improvement through genetic engineering. Here, we demonstrated that the orthologue of glucose sensors in the outstanding biocontrol fungus Trichoderma longibrachiatum SMF2, TlSTP1, participates in the regulation of peptaibols production. Deletion of Tlstp1 markedly impaired hyphal growth and conidiation, but significantly increased peptaibols yield by 5-fold for Trichokonins A and 2.6-fold for Trichokonins B. Quantitative real-time polymerase chain reaction analyses showed that the increased peptaibols production occurs at the transcriptional levels of the two nonribosomal peptide synthetase encoding genes, tlx1 and tlx2. Transcriptome analyses of the wild type and the Tlstp1 mutant strains indicated that TlSTP1 exerts a regulatory effect on a set of genes that are involved in a number of metabolic and cellular processes, including synthesis of several other secondary metabolites. These results suggest an important role of TlSTP1 in the regulation of vegetative growth and peptaibols production in T. longibrachiatum SMF2 and provide insights into construction of peptaibol-hyperproducing strains through genetic engineering.

10.
Medicine (Baltimore) ; 98(30): e16332, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348232

RESUMO

RATIONALE: Multiple primary carcinoma (MPM) refers to simultaneous or successive occurrence of ≥2 types of primary malignant tumors in a single organ or in different organs of the same individual. It is rarely seen in clinical practice. Among the various types of MPM, hilar cholangiocarcinoma combined with gastric cancer is extremely rare. PATIENT CONCERNS: The patient was a 61-year-old man who was admitted to our hospital due to upper abdominal discomfort and yellow-stained skin mucosa for 9 days. DIAGNOSES: Preoperative diagnosis: Considering the typical preoperative painless jaundice as well as his clinical imaging report, the patient received the following preoperative diagnosis: obstructive jaundice, type IV hilar cholangiocarcinoma based on Bismuth-Corlette classification, and no intrahepatic distant metastasis. Intraoperative diagnosis: The results of intraoperative snap freezing and laboratory examination indicated gastric adenocarcinoma. Therefore, the patient received an intraoperative diagnosis of obstructive jaundice, hilar cholangiocarcinoma, and gastric cancer. Postoperative pathological diagnosis: Postoperative pathological examination of the gastric lesion revealed the following results: ulcerative, moderately differentiated gastric adenocarcinoma and intestinal type in the Lauren classification of stomach cancer; moderately differentiated adenocarcinoma of the bile duct. INTERVENTIONS: Surgical resection operation was carried out and the patient received chemotherapy after operation. But we could not strictly follow the relevant clinical guidelines to perform standardized operations and provide comprehensive treatment because of his economic situation, psychological factors, and the current medical environment in China. OUTCOMES: The patient did not receive standardized postoperative therapy. Although he lived and worked normally for 8 months after the operation, he died 10 months after surgery. LESSONS: This report reminds us to pay close attention to the likelihood of MPM and other low-incidence diseases. The physicians and imaging clinicians should explore all clinical possibilities to avoid misdiagnosis of this rare disease and formulate effective treatment plans to maximize the therapeutic benefits for the patient.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Tumor de Klatskin/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Gástricas/patologia , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/cirurgia , Humanos , Icterícia Obstrutiva/etiologia , Tumor de Klatskin/complicações , Tumor de Klatskin/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Gástricas/cirurgia
11.
Mol Microbiol ; 112(4): 1145-1162, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31309604

RESUMO

Cellulase gene expression in Trichoderma reesei is highly responsive to environmental cues and is under stringent regulation by multiple transcription factors. XYR1 (Xylanase regulator 1) has been identified as the most important transcriptional activator of cellulase/hemicellulase gene expression although the precise transactivating mechanism remains largely elusive. Here we show that the activation domain of XYR1 interacts with the T. reesei homolog of the TrSNF12 subunit of SWI/SNF complex. Deletion of Trsnf12 markedly impaired the induced cellulase gene expression. Individual loss of other SWI/SNF subunits including the catalytic subunit also severely compromised cellulase gene expression and interfered with loss of histone H4 in the cbh1 and eg1 promoters upon cellulose induction. In addition, we find that the SWI/SNF occupancy on cellulase gene promoters strictly required XYR1 and TrSNF12 but TrSNF12 was dispensable for the XYR1 binding to these promoters. These data suggest a model in which XYR1 recruits SWI/SNF through direct interactions with TrSNF12 to remodel chromatin at cellulase gene promoters, thereby activating cellulase gene expression to initiate the cellulolytic response in T. reesei.

12.
Structure ; 27(8): 1286-1295.e4, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31230945

RESUMO

CD160 is a signaling molecule that interacts with herpes virus entry mediator (HVEM) and contributes to a wide range of immune responses, including T cell inhibition, natural killer cell activation, and mucosal immunity. GPI-anchored and transmembrane isoforms of CD160 share the same ectodomain responsible for HVEM engagement, which leads to bidirectional signaling. Despite the importance of the CD160:HVEM signaling axis and its therapeutic relevance, the structural and mechanistic basis underlying CD160-HVEM engagement has not been described. We report the crystal structures of the human CD160 extracellular domain and its complex with human HVEM. CD160 adopts a unique variation of the immunoglobulin fold and exists as a monomer in solution. The CD160:HVEM assembly exhibits a 1:1 stoichiometry and a binding interface similar to that observed in the BTLA:HVEM complex. Our work reveals the chemical and physical determinants underlying CD160:HVEM recognition and initiation of associated signaling processes.

13.
Methods Inf Med ; 58(1): 42-49, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31163452

RESUMO

OBJECTIVES: To investigate the performance of texture analysis in characterizing P53 mutations of hepatocellular carcinomas (HCCs) based on computed tomography (CT). METHODS: A total of 63 HCC patients underwent CT scans and were tested for P53 mutations. Patients were divided into two groups of P53(-) and P53(+) according to the P53 scores. First- and second-order texture features were computed from the CT images and compared between groups using independent Student's t-test. A Spearman's correlation coefficient was used for correlations to assess the relationship between the different P53 sores and CT data. The performance of texture features in differentiating the P53 mutations of HCC was assessed using receiver operating characteristic analysis. RESULTS: The mean values of angular second moment (ASM; mean = 0.001) and contrast (mean = 194.727) for P53(-) were higher than those of P53(+). Meanwhile the mean values of correlation (mean = 0.735), sum variance (mean = 1,111.052), inverse difference moment (IDM; mean = 0.090), and entropy (mean = 3.016) for P53(-) were lower than those of P53(+). Significant correlations were found between P53 scores and ASM (r = - 0.439), contrast (r = - 0.263), correlation (r = 0.551), sum of squares (r = 0.282), sum variance (r = 0.417), IDM (r = 0.308), and entropy (r = 0.569). Five texture parameters (ASM, contrast, correlation, IDM, and entropy) were predictive of P53 mutation status, with areas under the curve ranging from 0.621 to 0.792. CONCLUSIONS: There was a direct relationship between P53 mutations and gray-level co-occurrence matrix, but not with histograms for HCC patients. Correlation and entropy seemed to be the most promising in differentiating P53 (-) from P53(+).

14.
Chembiochem ; 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31243881

RESUMO

A new method has been developed to enhance the antibacterial efficiency of traditional antibiotics. Chloramphenicol-imprinted polymer particles were decorated with boronic acid to improve their binding to both Gram-negative and -positive bacteria. The polymer particles have a high antibiotic loading and provide a slow release of the antibiotic payload to deactivate the target bacteria. The boronic acid modified polymer particles not only contribute to enhanced antibacterial efficiency, but also have the potential to act as scavengers to remove unused antibiotic from the environment.

15.
Enzyme Microb Technol ; 127: 70-74, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31088620

RESUMO

D-glucuronic acid (GlcUA) is an important intermediate with numerous applications in the food, cosmetics, and pharmaceutical industries. Its biological production routes which employ myo-inositol oxygenase (MIOX) as the key enzyme are attractive. In this study, five diverse MIOX-encoding genes, from Cryptococcus neoformans, Chaetomium thermophilum, Arabidopsis thaliana, Thermothelomyces thermophila, and Mus musculus were overexpressed in Escherichia coli, respectively. A novel MIOX from Thermothelomyces thermophila (TtMIOX) exhibited high specific activity, and efficiently converted myo-inositol to GlcUA. Meanwhile, the degradation of GlcUA was inhibited by inactivation of uxaC from the Escherichia coli genome. Finally, the BWΔuxaC whole-cell biocatalyst harboring TtMIOX resulted in the production of 106 g/L GlcUA within 12 h in a 1-L bioreactor, corresponding to a conversion of 91% and productivity of 8.83 g/L/h. This study provides a feasible method for the industrial production of GlcUA.


Assuntos
Escherichia coli/metabolismo , Expressão Gênica , Ácido Glucurônico/metabolismo , Inositol Oxigenase/metabolismo , Inositol/metabolismo , Proteínas Recombinantes/metabolismo , Sordariales/enzimologia , Animais , Arabidopsis/enzimologia , Arabidopsis/genética , Biotransformação , Chaetomium/enzimologia , Chaetomium/genética , Cryptococcus neoformans/enzimologia , Cryptococcus neoformans/genética , Escherichia coli/genética , Inositol Oxigenase/genética , Camundongos , Proteínas Recombinantes/genética , Sordariales/genética
16.
Metab Eng ; 54: 244-254, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31063790

RESUMO

L-aspartate is an important 4-carbon platform compound that can be used as the precursor of numerous chemical products. The bioproduction of L-aspartate directly from biomass resources is expected to provide a more cost-competitive technique route. Yet little metabolic engineering work on this matter has been carried out. In this study, we designed a shortcut pathway of L-aspartate biosynthesis in Escherichia coli, with a maximized stoichiometric yield of 2 mol/mol glucose. L-aspartate aminotransferase (AspC) was overexpressed for producing L-aspartate and coexpressed with L-aspartate-a-decarboxylase (PanD) for producing L-aspartate's derivative ß-alanine. L-aspartate could only be detected after directing carbon flux towards oxaloacetate and blocking the "futile cycle" with TCA cycle. A cofactor self-sufficient system successfully improved the efficiency of AspC-catalyzing L-aspartate biosynthesis reaction, and the glucose uptake remolding capably decreased byproducts from pyruvate. More targets were modified for relieving the bottleneck during fed-batch bioconversion. As a result, 1.01 mol L-aspartate/mol glucose and 1.52 mol ß-alanine/mol glucose were produced in corresponding strains respectively. Fed-batch bioconversion allowed 249 mM (33.1 g/L) L-aspartate or 424 mM (37.7 g/L) ß-alanine production, respectively. The study provides a novel promising metabolic engineering route for the production of L-aspartate and its derivate chemicals using biomass resources. These results also represent the first report of the efficient bioproduction of L-aspartate directly from glucose in E. coli and the highest yield of ß-alanine reported so far.

17.
Appl Microbiol Biotechnol ; 103(11): 4511-4523, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30982107

RESUMO

XYR1 is the key transcription activator for cellulase gene expression in the model filamentous fungus Trichoderma reesei, which is widely applied in the industry due to its excellent capability of secreting a large quantity of cellulases. Despite the essential role of XYR1, the regulation of its expression in T. reesei cellulolytic response is poorly understood. In this study, we identified a transcription factor RXE1 exhibiting strong binding activity to the xyr1 promoter using yeast one-hybrid screen. RXE1 homologs exist in quite a few filamentous fungi but none of them have been assessed regarding their functional involvement in plant cell wall degradation. Knockdown of rxe1 in T. reesei using a copper-mediated RNAi system not only abrogated conidiation, but also remarkably compromised xyr1 and cellulase gene expression. The defective cellulase but not conidia production in the rxe1-knockdown strain was fully rescued by the constitutive expression of XYR1. Our study thus identified a novel transcriptional regulator controlling xyr1 and cellulase gene expression, which will contribute to elaborating the intricate network of cellulase gene regulation in T. reesei.


Assuntos
Celulase/biossíntese , Regulação Fúngica da Expressão Gênica , Genes Reguladores , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Trichoderma/genética , Trichoderma/metabolismo , Celulase/genética , DNA Fúngico/metabolismo , Técnicas de Silenciamento de Genes , Testes Genéticos , Regiões Promotoras Genéticas , Ligação Proteica
18.
Sensors (Basel) ; 19(6)2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30875910

RESUMO

In this paper, multiple resolvable group target tracking was considered in the frame of random finite sets. In particular, a group target model was introduced by combining graph theory with the labeled random finite sets (RFS). This accounted for dependence between group members. Simulations were presented to verify the proposed algorithm.

19.
Appl Environ Microbiol ; 85(5)2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30578269

RESUMO

The common soil cellulolytic bacterium known as Cytophaga hutchinsonii makes use of a unique but poorly understood strategy in order to utilize cellulose. While several genes have been identified as being an active part of the utilization of cellulose, the mechanism(s) by which C. hutchinsonii both (i) senses its environment and (ii) regulates the expression of those genes are not as yet known. In this study, we identified and characterized the gene CHU_3097 encoding an extracytoplasmic function (ECF) σ factor (σcel1), the disruption of which compromised C. hutchinsonii cellulose assimilation to a large degree. The σcel1 and its putative partner anti-σcel1, encoded by the CHU_3096 gene found immediately downstream from CHU_3097, copurified in vitro The σcel1 was discovered to be associated with inner membrane when cells were cultured on glucose and yet was partially released from the membrane in response to cellulose. This release was found to occur on glucose when the anti-σcel1 was absent. Transcriptome analyses found a σcel1-regulated, cellulose-responsive gene regulon, within which an outer membrane protein encoding the gene CHU_1276, essential for cellulose utilization, was discovered to be significantly downregulated by CHU_3097 disruption. The expression of CHU_1276 almost fully restored cellulose utilization to the CHU_3097 mutant, demonstrating that CHU_1276 represents a critical regulatory target of σcel1 In this way, our study provided insights into the role of an ECF σ factor in coordinating the cellulolytic response of C. hutchinsonii IMPORTANCE The common cellulolytic bacterium Cytophaga hutchinsonii uses a unique but poorly understood strategy in order to make use of cellulose. Throughout the process of cellulosic biomass breakdown, outer membrane proteins are thought to play key roles; this is evidenced by CHU_1276, which is required for the utilization of cellulose. However, the regulatory mechanism of its expression is not yet known. We found and characterized an extracytoplasmic function σ factor that is involved in coordinating the cellulolytic response of C. hutchinsonii by directly regulating the expression of CHU_1276 This study makes a contribution to our understanding of the regulatory mechanism used by C. hut chinsonii in order to adjust its genetic programs and so deal with novel environmental cues.

20.
Medicine (Baltimore) ; 97(52): e13730, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30593146

RESUMO

CASE SERIES: To analyze the clinical results and related factors of further surgical treatment for recurrent sacral chordomas.Chordomas are rare primary malignant tumors with a high recurrence rate. The treatment of recurrent tumors is difficult and controversial. Contamination by previous operations and disturbed local anatomical structures may increase the risk of reoperation. Most previous studies have focused on the primary tumor; there are very few reports on the clinical diagnosis, treatment, and prognosis of recurrent sacral chordomas.Thirty-four patients with recurrent sacral chordomas from 1979 to 2014 were included in this study. The patients comprised 25 men and 9 women with an average age of 50.7 (24-75) years. The average time until recurrence was 19.4 (4-51) months postoperatively, and 85.3% of the recurrent tumors were located in bone. The patients had an average of 1.2 (1-3) recurrences before further operations were performed in our hospital. The mean maximum tumor diameter was 8.1 (4.6-12.0) cm. Thirty-one patients underwent further tumor resection in our hospital. The postoperative recurrence, metastasis, and survival results were followed and analyzed.The mean follow-up after surgical treatment of recurrence was 49.6 (12-144) months. Nine patients (37.5%) developed recurrence again after an average of 26.7 months. The 3-year and 5-year recurrence-free survival rate was 69.4% and 63.1%, respectively. Multivariate analysis showed that the tumor level within the sacrum (P = .001) and the surgical margin (P = .001) were significant recurrence-related factors. Four patients (16.7%) developed lung metastasis. Eighteen patients were alive at last follow-up. The 5-year and 10-year survival rate after surgical treatment of recurrence was 67.3% and 53.9%, respectively.Most recurrent tumors are located in bone, and a safe osteotomy margin is important. The surgical margin is the only controllable factor of further tumor recurrence. Some patients with recurrence achieve long survival and obtain a clinical benefit from repeated operations if complete resection is achieved.


Assuntos
Cordoma/mortalidade , Recidiva Local de Neoplasia/mortalidade , Reoperação/mortalidade , Sacro , Neoplasias da Coluna Vertebral/mortalidade , Adulto , Idoso , Cordoma/patologia , Cordoma/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Sacro/patologia , Sacro/cirurgia , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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