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1.
J Org Chem ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645268

RESUMO

An unprecedented method for the synthesis of dichlorinated and dibrominated 2-amino-substituted chromanones is developed by employing enaminones and NCS/NBS as starting materials under microwave irradiation. The reactions proceed quickly to deliver products without using any catalyst or additive, thus providing practical access to 3,3-dihalogenated 2-aminochromanones.

2.
Eur J Radiol ; 144: 109981, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34624648

RESUMO

OBJECTIVES: To investigate the value of combining clinicopathological characteristics with computed tomographic (CT) features of tumours for predicting occult lymph node metastasis (OLNM) in peripheral solid non-small cell lung cancer (PS-NSCLC). METHODS: The study included 478 NSCLC clinically N0 (cN0) patients who underwent lobectomy and systemic lymph node dissection from January 2014 to August 2019. Patients were classified into OLNM and negative lymph node metastasis (NLNM) groups. The CT features of non-metastatic and metastatic lymph nodes with a largest short-diameter > 5 mm were compared in the OLNM group. Thereafter, the clinicopathological characteristics and CT morphological features of tumours were compared between both groups. Multivariable logistic regression analysis and receiver-operating characteristic curve were developed. RESULTS: CT images detected 103 metastatic and 705 non-metastatic lymph nodes, and no significant differences in CT features of lymph nodes were found in all 161 OLNM patients (P > 0.05). For both groups, sex, carcinoembryonic antigen and pathological type differed significantly (all P < 0.05), while tumour size, necrosis, calcification, vascular convergence, pleural involvement, and the shortest interval of tumour-pleura differed significantly on CT images (all P < 0.05). Multivariable logistic regression analysis showed that carcinoembryonic antigen > 5.00 ng/ml, adenocarcinoma, absence of vascular convergence, and pleural involvement of Type II (one linear or cord-like pleural tag or tumour abut to the pleura with a broad base observed on both lung and mediastinal window images) were independent predicting factors of OLNM. CONCLUSIONS: CT findings of lymph nodes can provide limited value and integrating clinicopathological characteristics with the CT morphological features of tumours is helpful in predicting OLNM in patients with PS-NSCLC.

3.
Eur J Med Chem ; 226: 113817, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34537445

RESUMO

Glioblastoma is one of the most lethal brain tumors. The crucial chemotherapy is mainly alkylating agents with modest clinical success. Given this desperate need and inspired by the encouraging results of a phase II trial via concomitant Topo I inhibitor plus COX-2 inhibitor, we designed a series of N-2-(phenylamino) benzamide derivatives as novel anti-glioblastoma agents based on structure modification on 1,5-naphthyridine derivatives (Topo I inhibitors). Notably, the target compounds I-1 (33.61 ± 1.15 µM) and I-8 (45.01 ± 2.37 µM) were confirmed to inhibit COX-2, while a previous reported compound (1,5-naphthyridine derivative) resulted nearly inactive towards COX-2 (IC50 > 150 µM). Besides, I-1 and I-8 exhibited higher anti-proliferation, anti-migration, anti-invasion effects than the parent compound 1,5-naphthyridine derivative, suggesting the success of modification based on the parent. Moreover, I-1 obviously repressed tumor growth in the C6 glioma orthotopic model (TGI = 66.7%) and U87MG xenograft model (TGI = 69.4%). Besides, I-1 downregulated PGE2, VEGF, MMP-9, and STAT3 activation, upregulated E-cadherin in the orthotopic model. More importantly, I-1 showed higher safety than temozolomide and different mechanism from temozolomide in the C6 glioma orthotopic model. All the evidence demonstrated that N-2-(phenylamino) benzamide derivatives as novel anti-glioblastoma agents could be promising for the glioma management.

4.
Infect Immun ; 89(11): e0022421, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34370510

RESUMO

The immunomes of Ehrlichia chaffeensis and Ehrlichia canis have recently been revised to include immunodominant hypothetical proteins with conformational antibody epitopes. In this study, we examined 216 E. chaffeensis and 190 E. canis highly antigenic proteins according to ANTIGENpro and also performed a genome-wide hypothetical protein analysis (E. chaffeensis n = 104; E. canis n = 124) for immunoreactivity. Using cell-free protein expression and immunoanalysis, 118 E. chaffeensis and 39 E. canis proteins reacted with sera from naturally E. chaffeensis-infected patients or E. canis-infected dogs. Moreover, 22 E. chaffeensis and 18 E. canis proteins consistently and strongly reacted with a panel of patient or canine sera. A subset of E. chaffeensis (n = 18) and E. canis (n = 9) proteins were identified as immunodominant. Consistent with our previous study, most proteins were classified as hypothetical, and the antibody epitopes exhibited complete or partial conformation dependence. The majority (28/40, 70%) of E. chaffeensis and E. canis proteins contained transmembrane domains, and 19 (48%) were predicted to be secreted effectors. The antigenic repertoires of E. chaffeensis and E. canis were mostly diverse and suggest that the immunomes of these closely related ehrlichiae are dominated by species-specific conformational antibody epitopes. This study reveals a significant group of previously undefined E. chaffeensis and E. canis antigens and reaffirms the importance of conformation-dependent epitopes as targets of anti-Ehrlichia immune responses. These findings substantially expand our understanding of host-Ehrlichia immune responses, advance efforts to define the molecular features of protective proteins, and improve prospects for effective vaccines for the ehrlichioses.

5.
Nat Commun ; 12(1): 3583, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117225

RESUMO

Construction of C-C bonds via reductive coupling of aldehydes and ketones is hindered by the highly negative reduction potential of these carbonyl substrates, particularly ketones, and this renders the formation of ketyl radicals extremely endergonic. Here, we report the efficient activation of carbonyl compounds by the formation of specific host-guest interactions in a hydroxyl-decorated porous photocatalyst. MFM-300(Cr) exhibits a band gap of 1.75 eV and shows excellent catalytic activity and stability towards the photoreductive coupling of 30 different aldehydes and ketones to the corresponding 1,2-diols at room temperature. Synchrotron X-ray diffraction and electron paramagnetic resonance spectroscopy confirm the generation of ketyl radicals via confinement within MFM-300(Cr). This protocol removes simultaneously the need for a precious metal-based photocatalyst or for amine-based sacrificial agents for the photochemical synthesis.

6.
Acta Pharmacol Sin ; 42(10): 1690-1702, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34112960

RESUMO

Ferroptotic cell death is characterized by iron-dependent lipid peroxidation that is initiated by ferrous iron and H2O2 via Fenton reaction, in which the role of activating transcription factor 3 (ATF3) remains elusive. Brucine is a weak alkaline indole alkaloid extracted from the seeds of Strychnos nux-vomica, which has shown potent antitumor activity against various tumors, including glioma. In this study, we showed that brucine inhibited glioma cell growth in vitro and in vivo, which was paralleled by nuclear translocation of ATF3, lipid peroxidation, and increases of iron and H2O2. Furthermore, brucine-induced lipid peroxidation was inhibited or exacerbated when intracellular iron was chelated by deferoxamine (500 µM) or improved by ferric ammonium citrate (500 µM). Suppression of lipid peroxidation with lipophilic antioxidants ferrostatin-1 (50 µM) or liproxstatin-1 (30 µM) rescued brucine-induced glioma cell death. Moreover, knockdown of ATF3 prevented brucine-induced accumulation of iron and H2O2 and glioma cell death. We revealed that brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H2O2 accumulation via upregulating NOX4 and SOD1 to generate H2O2 on one hand, and downregulating catalase and xCT to prevent H2O2 degradation on the other hand. H2O2 then contributed to brucine-triggered iron increase and transferrin receptor upregulation, as well as lipid peroxidation. This was further verified by treating glioma cells with exogenous H2O2 alone. Moreover, H2O2 reversely exacerbated brucine-induced ER stress. Taken together, ATF3 contributes to brucine-induced glioma cell ferroptosis via increasing H2O2 and iron.

7.
Molecules ; 26(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068822

RESUMO

The contribution of rheological properties and viscoelasticity of the interfacial adsorbed layer to the emulsification mechanism of enzymatic modified sugar beet pectin (SBP) was studied. The component content of each enzymatic modified pectin was lower than that of untreated SBP. Protein and ferulic acid decreased from 5.52% and 1.08% to 0.54% and 0.13%, respectively, resulting in a decrease in thermal stability, apparent viscosity, and molecular weight (Mw). The dynamic interfacial rheological properties showed that the interfacial pressure and modulus (E) decreased significantly with the decrease of functional groups (especially proteins), which also led to the bimodal distribution of particle size. These results indicated that the superior emulsification property of SBP is mainly determined by proteins, followed by ferulic acid, and the existence of other functional groups also promotes the emulsification property of SBP.


Assuntos
Beta vulgaris/química , Emulsões/química , Enzimas/metabolismo , Pectinas/metabolismo , Reologia , Adsorção , Difusão , Elasticidade , Cinética , Peso Molecular , Óleos/química , Tamanho da Partícula , Pressão , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Termogravimetria , Fatores de Tempo , Viscosidade , Água/química
8.
BMC Med Imaging ; 21(1): 81, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33985454

RESUMO

BACKGROUND: Necrotic pulmonary lesions manifest as relatively low-density internally on contrast-enhanced computed tomography (CT). However, using CT to differentiate malignant and benign necrotic pulmonary lesions is challenging, as these lesions have similar peripheral enhancement. With the introduction of dual-energy spectral CT (DESCT), more quantitative parameters can be obtained and the ability to differentiate material compositions has been highly promoted. This study investigated the use of kVp-switching DESCT in differentiating malignant from benign necrotic lung lesions. METHODS: From October 2016 to February 2019, 40 patients with necrotic lung cancer (NLC) and 31 with necrotic pulmonary mass-like inflammatory lesion (NPMIL) were enrolled and underwent DESCT. The clinical characteristics of patients, CT morphological features, and DESCT quantitative parameters of lesions were compared between the two groups. Binary logistic regression analysis was performed to identify the independent prognostic factors differentiating NPMIL from NLC. Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of single-parameter and multiparametric analyses. RESULTS: Significant differences in age, C-reactive protein concentration, the slope of the spectral curve from 40 to 65 keV (K40-65 keV) of necrosis in non-contrast-enhanced scanning (NCS), arterial phase (AP) and venous phase (VP), effective atomic number of necrosis in NCS, and iodine concentration (IC) of the solid component in VP were observed between groups (all p < 0.05). The aforementioned parameters had area under the ROC curve (AUC) values of 0.747, 0.691, 0.841, 0.641, 0.660, 0.828, and 0.754, respectively, for distinguishing between NLC and NPMIL. Multiparametric analysis showed that age, K40-65 keV of necrosis in NCS, and IC of the solid component in VP were the most effective factors for differentiating NLC from NPMIL, with an AUC of 0.966 and percentage of correct class of 88.7%. CONCLUSIONS: DESCT can differentiate malignant from benign necrotic lung lesions with a relatively high accuracy.

9.
Int J Biol Macromol ; 183: 1621-1629, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34000314

RESUMO

The aim of the present study was to investigate the effect of glycosylation with sugar beet pectin (SBP) on the interfacial behaviour and emulsifying ability of coconut protein (CP). The physical stabilities of the emulsions were predicted by transmission variation, droplet distribution and zeta potentials. The results showed that SBP-CP-stabilized emulsions showed better stability during centrifugation than those stabilized by CP because SBP-CP reduced the degree of variation in the CP transmission profile. The adsorption kinetics of all emulsifiers at the oil-water interface were determined to investigate the relationship between the interfacial behaviour and emulsion stability. The presence of SBP considerably reduced the adsorption rate of CP (0.698 mN/m/s1/2) and hampered the development of a highly viscoelastic network at the oil-water interface. The values of the dilatational elastic modulus (Ed = 19.477 mN/m) and dilatational viscous modulus (E = 19.719 mN/m) were approximately equal, indicating that the adsorption process was mainly dominated by elastic behaviour. Additionally, the SBP-CP interaction enhanced the dilatational property of the CP-absorbed layer.


Assuntos
Beta vulgaris/metabolismo , Cocos/metabolismo , Emulsificantes/química , Pectinas/química , Proteínas de Plantas/química , Adsorção , Emulsões , Glicosilação , Cinética , Tamanho da Partícula , Reologia , Tensão Superficial , Viscosidade
10.
Acta Pharmacol Sin ; 42(8): 1324-1337, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33879840

RESUMO

FOXO3a (forkhead box transcription factor 3a) is involved in regulating multiple biological processes in cancer cells. BNIP3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) is a receptor accounting for priming damaged mitochondria for autophagic removal. In this study we investigated the role of FOXO3a in regulating the sensitivity of glioma cells to temozolomide (TMZ) and its relationship with BNIP3-mediated mitophagy. We showed that TMZ dosage-dependently inhibited the viability of human U87, U251, T98G, LN18 and rat C6 glioma cells with IC50 values of 135.75, 128.26, 142.65, 155.73 and 111.60 µM, respectively. In U87 and U251 cells, TMZ (200 µM) induced DNA double strand breaks (DSBs) and nuclear translocation of apoptosis inducing factor (AIF), which was accompanied by BNIP3-mediated mitophagy and FOXO3a accumulation in nucleus. TMZ treatment induced intracellular ROS accumulation in U87 and U251 cells via enhancing mitochondrial superoxide, which not only contributed to DNA DSBs and exacerbated mitochondrial dysfunction, but also upregulated FOXO3a expression. Knockdown of FOXO3a aggravated TMZ-induced DNA DSBs and mitochondrial damage, as well as glioma cell death. TMZ treatment not only upregulated BNIP3 and activated autophagy, but also triggered mitophagy by prompting BNIP3 translocation to mitochondria and reinforcing BNIP3 interaction with LC3BII. Inhibition of mitophagy by knocking down BNIP3 with SiRNA or blocking autophagy with 3MA or bafilomycin A1 exacerbated mitochondrial superoxide and intracellular ROS accumulation. Moreover, FOXO3a knockdown inhibited TMZ-induced BNIP3 upregulation and autophagy activation. In addition, we showed that treatment with TMZ (100 mg·kg-1·d-1, ip) for 12 days in C6 cell xenograft mice markedly inhibited tumor growth accompanied by inducing FOXO3a upregulation, oxidative stress and BNIP3-mediated mitophagy in tumor tissues. These results demonstrate that FOXO3a attenuates temozolomide-induced DNA double strand breaks in human glioma cells via promoting BNIP3-mediated mitophagy.

11.
mSphere ; 6(2)2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33883266

RESUMO

Ehrlichia chaffeensis expresses the TRP120 multifunctional effector, which is known to play a role in phagocytic entry, on the surface of infectious dense-cored ehrlichiae, but a cognate host receptor has not been identified. We recently reported that E. chaffeensis activates canonical Wnt signaling in monocytes to promote bacterial uptake and intracellular survival and that TRP120 was involved in this activation event. To identify the specific mechanism of pathway activation, we hypothesized that TRP120 is a Wnt signaling ligand mimetic that initiates Wnt pathway activity through direct interaction with the Wnt pathway Frizzled family of receptors. In this study, we used confocal immunofluorescence microscopy to demonstrate very strong colocalization between E. chaffeensis and Fzd2, 4, 5, 7, and 9 as well as coreceptor LRP5 at 1 to 3 h postinfection. Direct binding between TRP120 and multiple Fzd receptors was further confirmed by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR). Interfering RNA knockdown of Wnt receptors, coreceptors, and signaling pathway components significantly reduced E. chaffeensis infection, demonstrating that complex and redundant interactions are involved in Wnt pathway exploitation. We utilized in silico approaches to identify a repetitive short linear motif (SLiM) in TRP120 that is homologous to Wnt ligands and used mutant SLiM peptides and an α-TRP120-Wnt-SLiM antibody to demonstrate that the TRP120 Wnt SLiM activates the canonical Wnt pathway and promotes E. chaffeensis infection. This study reports the first example of bacterial mimicry of Wnt pathway ligands and highlights a pathogenic mechanism with potential for targeting by antimicrobial therapeutics.IMPORTANCE Upon infecting mammalian hosts, Ehrlichia chaffeensis establishes a replicative niche in microbe-eating immune system cells where it expertly orchestrates infection and spread. One of the ways Ehrlichia survives within these phagocytes is by activating evolutionarily conserved signaling pathways including the Wnt pathway; however, the molecular details of pathway hijacking have not been defined. This study is significant because it identifies an ehrlichial protein that directly interacts with components of the Wnt receptor complex, influencing pathway activity and promoting infection. Consequentially, Ehrlichia serves as a unique tool to investigate the intricacies of how pathogens repurpose human immune cell signaling and provides an opportunity to better understand many cellular processes in health and disease. Furthermore, understanding how this bacterium utilizes its small genome to survive within cells that evolved to destroy pathogens will facilitate the development of antibacterial therapeutics that could target Ehrlichia as well as other intracellular agents of human disease.

12.
Acta Trop ; 219: 105931, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33901440

RESUMO

Ehrlichia spp. are important tick-borne pathogens of animals in Brazil, and Ehrlichia canis is the most prevalent species infecting dogs. Moreover, Ehrlichia minasensis has also recently been identified as a novel ehrlichial agent that infects cattle in Brazil. The objective of this study was to determine whether dogs could be infected by E. minasensis. To investigate this possibility, sera (n = 429) collected from dogs in the Pantanal region were retrospectively analyzed for the presence of antibodies against E. canis and E. minasensis. Canine sera were screened by two isolates of E. canis in indirect immunofluorescence assay (IFA) and the majority (n = 298; 69.4%) had antibodies with endpoint titers ranging from 80 to 327,680. In order to further confirm E. canis-specific antibodies, IFA positive sera were analyzed by ELISA using E. canis-specific peptides (i.e. TRP19 and TRP36 US/BR/CR), which detected E. canis antibodies in 80.2% (239/298) of the dog sera. Fifty-nine (13.7%) samples had detectable antibodies to E. canis by IFA but were negative by E. canis peptide ELISA. These sera were then tested by E. minasensis IFA (Cuiaba strain) as antigen and 67.8% (40/59) were positive (titers ranging from 80 to 20,480). Eleven sera had antibody titers against E. minasensis at least two-fold higher than observed for E. canis and suggests that these dogs were previously infected with E. minasensis. The results of the present study suggest that multiple ehrlichial agents infect dogs in Brazil, which highlights the need to consider different Ehrlichia spp. in Brazilian dogs, particularly in areas where dogs are frequently exposed to multiple tick species. This investigation is the first to provide serologic evidence of E. minasensis infection in dogs from Brazil.


Assuntos
Doenças do Cão/diagnóstico , Ehrlichia/fisiologia , Ehrlichiose/veterinária , Testes Sorológicos , Animais , Anticorpos Antibacterianos/sangue , Bovinos , Doenças do Cão/imunologia , Cães , Ehrlichia/imunologia , Ehrlichiose/diagnóstico , Ehrlichiose/imunologia
13.
Cancer Med ; 10(7): 2268-2285, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33660378

RESUMO

In this study, we developed a long noncoding RNA (lncRNA)-based prognostic signature for stratification of patients with head a nd neck squamous cell carcinoma (HNSCC). In total, 493 HNSCC samples obtained from the Cancer Genome Atlas database were divided into training and testing cohorts (3:2 ratio). We identified 3913 immune-related lncRNAs in the HNSCC training cohort by Pearson correlation analysis; only seven were independently associated with overall survival and were used to develop an immune-related lncRNA prognostic signature (IRLPS) grouping of HNSCC patients into high- and low-IRLPS subgroups. Univariate and multivariate Cox analyses revealed that low-IRLPS patients had a better prognosis in all the cohorts, which was retained after stratification by sex, grade, and HPV status. Although the TNM stage was also an independent prognostic factor, the IRLPS had a better discriminability with higher AUC at the 3- and 5-year follow-ups in all cohorts. Low-IRLPS samples had more immune cell infiltration and were enriched in immune-related pathways, while high- IRLPS samples were enriched in metabolic pathways. A nomogram constructed including age, TNM stage, and IRLPS showed good calibration. Thus, IRLPS improves the prognostic prediction and also distinguishes different tumor microenvironment (TME) in HNSCC patients.


Assuntos
Neoplasias de Cabeça e Pescoço/genética , Nomogramas , RNA Longo não Codificante/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Fatores Etários , Idoso , Bases de Dados Genéticas , Feminino , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imunidade Celular , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Fatores Sexuais , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Análise de Sobrevida , Transcriptoma
14.
CNS Neurosci Ther ; 27(7): 792-804, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33764684

RESUMO

AIMS: The basal forebrain (BF) plays an essential role in wakefulness and cognition. Two subtypes of BF gamma-aminobutyric acid (GABA) neurons, including somatostatin-expressing (GABASOM ) and parvalbumin-positive (GABAParv ) neurons, function differently in mediating the natural sleep-wake cycle. Since the loss of consciousness induced by general anesthesia and the natural sleep-wake cycle probably share similar mechanisms, it is important to clarify the accurate roles of these neurons in general anesthesia procedure. METHODS: Based on two transgenic mouse lines expressing SOM-IRES-Cre and PV-IRES-Cre, we used a combination of genetic activation, inactivation, and chronic ablation approaches to further explore the behavioral and electroencephalography (EEG) roles of BFSOM and BFParv neurons in general anesthesia. After a single intravenous injection of propofol and the induction and recovery times of isoflurane anesthesia, the anesthesia time was compared. The changes in cortical EEG under different conditions were also compared. RESULTS: Activation of BF GABASOM neurons facilitates both the propofol and isoflurane anesthesia, manifesting as a longer anesthesia duration time with propofol anesthesia and a fast induction time and longer recovery time with isoflurane anesthesia. Moreover, BF GABASOM -activated mice displayed a greater suppression of cortical electrical activity during anesthesia, showing an increase in δ power bands or a simultaneous decrease in high-frequency power bands. However, only a limited and nuanced effect on propofol and isoflurane anesthesia was observed with the manipulated BF GABAParv neurons. CONCLUSIONS: Our results suggested that BF GABASOM neurons play a critical role in propofol and isoflurane general anesthesia, while BF GABAParv neurons appeared to have little effect.

15.
Water Res ; 194: 116909, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33609905

RESUMO

In this work, a rhamnolipid (RL) pretreatment technology was proposed to promote methane production from two-phase anaerobic digestion of waste activated sludge. In the first phase (i.e., acidogenic phase), the WAS hydrolysis and acidogenesis were significantly enhanced after RL pretreatment for 4 day, under which the concentration of soluble protein and the short-chain fatty acids (SCFA) in the presence of RL at 0.04 g/g TSS was respectively 2.50 and 5.02 times higher than that without RL pretreatment. However, methane production was inhibited in the presence of RL. In the second phase (i.e., methanogenic phase), batch biochemical methane potential tests suggested that the addition of RL is effective in promoting anaerobic methane production. With an increase of RL dosage from 0 to 0.04 g/g TSS, the cumulative methane yield increased from 100.42 ± 3.01 to 168.90 ± 5.42 mL. Although the added RL could be utilized to produce methane, it was not the major contributor to the enhancement of methane yield. Further analysis revealed that total cumulative yield from the entire two-phase anaerobic digestion (sum of the yield of the acidogenic phase and methanogenic phase) increased from 113.42 ± 3.56 to 164.18 ± 5.20 mL when RL dosage increased from 0 to 0.03 g/g TSS, indicating that the addition of RL induced positive effect on the methane production of the entire two-phase anaerobic digestion. The enzyme activity analysis showed that although higher dosages of RL still inhibited the microorganisms related to methanogenesis to some extends in the methanogenic phase, the inhibitory effect was significantly weakened compared to the acidogenic phase. Microbial analysis revealed that RL reduced the abundance of Candidatus_Methanofastidiosum sp. while increased the abundance of Methanosaeta sp., causing the major methanogenesis pathway to change from hydrogenotrophic to aceticlastic. Moreover, the community of hydrolytic microbes and acidogens was shifted in the direction that is conducive to hydrolysis-acidogenesis. The findings reported not only expand the application field of RL, but also may provide supports for sustainable operation of wastewater treatment plants (WWTPs).


Assuntos
Esgotos , Eliminação de Resíduos Líquidos , Anaerobiose , Reatores Biológicos , Glicolipídeos , Metano
16.
Dalton Trans ; 50(9): 3116-3120, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33565539

RESUMO

The kinetics of hydrolysis of dimethyl nitrophenyl phosphate (DMNP), a simulant of the nerve agent Soman, was studied and revealed transition metal salts as catalysts. The relative rates of DMNP hydrolysis by zirconium and hafnium chlorides are in accordance with their Lewis acidity. In situ conversion of zirconium chloride to zirconium oxy-hydroxide was identified as the key step. We propose a precursor-MOF activity relationship.

17.
BMC Cancer ; 21(1): 188, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622258

RESUMO

BACKGROUND: Gastric outlet obstruction (GOO) is a late complication of advanced gastric cancer, and it is controversial how to select the therapeutic strategies: gastrojejunostomy and palliative gastrectomy? Therefore, this study was to compare the surgical and survival outcomes of gastrojejunostomy and palliative gastrectomy. METHODS: In total, 199 gastric cancer patients with outlet obstruction treated by surgery between January 2000 and December 2015 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Patients were divided into gastrojejunostomy group and palliative gastrectomy group. Propensity score matching (PSM) was performed to balance the selection bias. RESULTS: After 1:1 PSM, a total of 104 patients were included for final analysis. The median overall survival (OS) times in the gastrojejunostomy group and palliative gastrectomy group were 8.50 and 11.87 months, respectively (P = 0.243). The postoperative complication rates in the gastrojejunostomy group and palliative gastrectomy group were 19.23% (10/52) and 17.31% (9/52), respectively (P = 0.800), and no treatment-related death was observed. Multivariate analysis showed that periton0eal seeding (P = 0.014) and chemotherapy (P < 0.001) were independent prognostic factors. Among them, peritoneal seeding was a risk factor and postoperative chemotherapy was a protective factor. CONCLUSIONS: Our results indicated that although the surgical complications of palliative gastrectomy were manageable, it showed no survival benefit. Therefore, relieving obstruction symptom, improving patients' quality of life and creating better conditions for chemotherapy appear to be the main therapeutic strategies for advanced gastric cancer with GOO.


Assuntos
Gastrectomia/métodos , Derivação Gástrica/métodos , Obstrução da Saída Gástrica/cirurgia , Cuidados Paliativos , Pontuação de Propensão , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrectomia/efeitos adversos , Derivação Gástrica/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/mortalidade
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(1): 82-86, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33474894

RESUMO

Objective: In order to better understand the role of mechanical stress in early tooth development, we examined the spatiotemporal expression patterns of mechanical-stress related regulatory protein (actin filament, or F-actin), non-muscle myosin ⅡB (NMⅡB) and vinculin at different stages of tooth development in mice. Methods: Mouse first mandible molars were used as the research model. Immunofluorescence staining was performed to detect the expression patterns of F-actin, NMⅡB and Vinculin, the key molecules constituting the chemical mechanical system, at bud, cap, early bell and late bell stages of tooth. Results: F-actin, NMⅡB and vinculin were all expressed in the tooth epithelium in an extensive or a limited way at different stages of tooth development, while F-actin was also expressed steadily in the mesenchymal cells. The quantitative analysis of fluorescence intensity showed that F-actin and NMⅡB exhibited significantly increase in the early stage of tooth development, but then dropped to their basal levels at the end of the late bell stage and the early bell stage respectively, with the differences of expression changes between successive developmental stages showing statistically significance ( P<0.05). Vinculin expression, however, remained at a relatively constant level except for the late bell stage when vinculin expression was slightly elevated compared to that of the early bell stage ( P<0.05). Conclusions: The findings suggest that mechanical stress is involved in early tooth development. F-actin may have an important role in dispersing and transmitting mechanical stress while NMⅡB may participate in tooth epithelial invagination and cusps formation. The findings also suggest that vinculin can respond to the mechanical stimuli and its interaction with cell adhesion molecules may play a role in tooth development. The mechanism of how actomyosin and cell adhesion interact with each other in regulating tooth development still needs further investigation.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Odontogênese , Animais , Epitélio , Camundongos , Dente Molar , Odontogênese/genética , Estresse Mecânico
19.
Dev Comp Immunol ; 118: 103996, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33444646

RESUMO

Interferon regulatory factors (IRFs) are crucial transcription factors involved in transcriptional regulation of type I interferons (IFNs) and IFN-stimulated genes (ISGs) against viral infection. In teleost fish, eleven IRFs have been found, however, understanding of their roles in the antiviral response remains limited. In the previous study, IRF1 (LcIRF1) and IRF2 (LcIRF2) genes were cloned from large yellow croaker (Larimichthys crocea). Here, we further characterized their function in the antiviral response. LcIRF1 and LcIRF2 were constitutively expressed in primary head kidney monocytes/macrophages (PKMs), lymphocytes (PKLs), granulocytes (PKGs) and large yellow croaker head kidney (LYCK) cell line, and significantly upregulated in PKMs and LYCK cells after stimulation with poly (I:C). LcIRF1 could induce promoter activities of three large yellow croaker type I IFNs, IFNc, IFNd and IFNh, while LcIRF2 could only induce those of IFNd and IFNh, and inhibit IFNc promoter activity. Correspondingly, overexpression of LcIRF1 in LYCK cells increased expression of all three IFNs (IFNc, IFNd and IFNh), while that of LcIRF2 only upregulated the expression levels of IFNd and IFNh, and inhibited expression of IFNc, although both LcIRF1and LcIRF2 induced expression of IFN-stimulated genes (ISGs), MxA, PKR and Viperin. Additionally, both LcIRF1 and LcIRF2 inhibited the Spring Viremia of Carp Virus (SVCV) replication in epithelioma papulosum cyprinid (EPC) cells, thus showing antiviral activity. Taken together, these results indicated that both LcIRF1 and LcIRF2 play positive roles in regulating the antiviral response of large yellow croaker by induction of distinct subgroups of type I IFNs.

20.
Eur J Med Chem ; 211: 113027, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33248852

RESUMO

The combination between two well-studied bioactive compounds melatonin and salicylic acid with proper modifications unexpectedly creates a sharp pair of "scissors" cutting off the vicious connection between inflammation and cancer by targeting a key contributor Signal Transducers and Activators of Transcription 3 (STAT3) in the two pathological processes. A representative compound P-3 with IC50 values on each tested cell line ranging from 7.37 to 18.62 µM among the designed melatonin derivatives is equipped with the ability of curbing inflammation-promoting cancer by down-regulating the expression, activation and nuclear translocation of STAT3, breaking the feedforward loop of STAT3 activation by decreasing the expression of pro-tumorigenic cytokines, and inducing cell apoptosis through ROS triggered Cyto-c/Caspase-3 pathway. This study suggests that the melatonin derivative P-3 is likely to become a promising chemical structure for developing the novel anti-cancer agents taking effect through hindering the mutual-promoting processes between inflammation and cancer.


Assuntos
Antineoplásicos/farmacologia , Inflamação/tratamento farmacológico , Melatonina/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Inflamação/metabolismo , Inflamação/patologia , Melatonina/síntese química , Melatonina/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
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