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1.
Bioorg Chem ; 99: 103795, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32240871

RESUMO

Eight new alkaloids, including five isoquinoline alkaloids, a benzoazepine alkaloid, two isoindole alkaloids, and three synthetic alkaloids firstly obtained from the natural sources, together with three known ones were isolated from the bulbs of Corydalis decumbens. The structures were determined by analysis of their spectroscopic data and single-crystal X-ray diffraction. This is the first report of isoindole alkaloid and benzoazepine alkaloid from the genus Corydalis. Full NMR data for 9-11 are reported here for the first time. Moreover, the ability to modulate neuronal Ca2+ mobilization of the isolated alkaloids was tested in primary cultured neocortical neurons. Compound 7 inhibited spontaneous Ca2+ oscillations in primary neocortical neuron cultures at low micromolar concentrations.

2.
Clin Cancer Res ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127394

RESUMO

PURPOSE: Patient-reported outcomes (PROs) were evaluated in the phase 3 IMmotion151 trial (NCT02420821) to inform overall treatment/disease burden of atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (mRCC). EXPERIMENTAL DESIGN: Patients were randomized 1:1 to receive atezolizumab 1200 mg IV q3w plus bevacizumab 15 mg/kg IV q3w or sunitinib 50 mg PO QD 4 weeks on/2 weeks off. Patients completed the MD Anderson Symptom Inventory (MDASI), National Comprehensive Cancer Network Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI-19), and Brief Fatigue Inventory (BFI) at baseline, q3w during treatment, at end-of-treatment, and during survival follow-up. Longitudinal and time to deterioration (TTD) analyses for core and RCC symptoms and their interference with daily life, treatment side-effect bother, and health-related quality of life (HRQOL) were evaluated. RESULTS: The ITT population included 454 and 461 patients in the atezolizumab plus bevacizumab and sunitinib arms, respectively. Completion rates for each instrument were 83%-86% at baseline and ≥ 70% through week 54. Milder symptoms, less symptom interference and treatment side-effect bother, and better HRQOL at most visits were reported with atezolizumab plus bevacizumab versus sunitinib. The TTD HR (95% CI) favored atezolizumab plus bevacizumab for core (HR, 0.50 [0.40, 0.62]) and RCC symptoms (HR, 0.45 [0.37, 0.55]); symptom interference (HR, 0.56 [0.46, 0.68]); and HRQOL (HR, 0.68 [0.58, 0.81]). CONCLUSION: PROs in IMmotion151 suggest lower overall treatment burden with atezolizumab plus bevacizumab compared with sunitinib in patients with treatment-naive mRCC and provide further evidence for clinical benefit of this regimen.

3.
J Endovasc Ther ; : 1526602820910135, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32166999

RESUMO

Purpose: To compare characteristics of acute, subacute, and chronic type B aortic dissection and their influence on long-term results of thoracic endovascular aortic repair (TEVAR). Materials and Methods: In a single-center, retrospective cohort study, 314 patients (median age 52 years; 244 men) with acute (n=165), subacute (n=115), or chronic (n=34) type B aortic dissection underwent TEVAR between January 2009 and December 2013. Patient demographics, risk factors, and imaging characteristics were compared among the groups. Univariable and multivariable Cox regression analyses were performed to identify any factors influencing survival. Results: The acute and subacute patients exhibited more complications at presentation than chronic patients. However, the chronic patients exhibited more aneurysmal dilatation (p<0.001) and true lumen collapse (p<0.001). Over a mean follow-up of 68.1±22.9 months (range 2-108), subacute patients showed a lower reintervention rate (3.6% vs 12.1% vs 12.1%, p=0.045), a lower major complication rate (14.4% vs 33.1% vs 27.3%, p=0.002), and better cumulative overall survival (p=0.03) than the acute and chronic groups, respectively. Furthermore, acute patients developed more stent-graft-induced distal erosion (p=0.017) and retrograde type A dissection (RTAD) (p=0.036), whereas chronic patients had less aortic remodeling in the stented segment (p<0.001), distal thoracic aorta (p<0.001), and abdominal aorta (p=0.047). Finally, multivariable analysis demonstrated age >52 years, visceral malperfusion, and RTAD as independent factors influencing overall survival; aneurysmal dilatation, rupture/impending rupture, and RTAD were independent factors influencing aorta-specific survival. Conclusion: Acute and subacute patients had increased risks of rupture and complications at presentation, whereas chronic patients had increased risks for aneurysmal dilatation. From a long-term perspective, the subacute phase might be an optimal time for TEVAR in cases of type B aortic dissection that do not need emergent interventions. The risk factors influencing survival should be identified, carefully managed, and possibly prevented.

4.
Mikrochim Acta ; 187(4): 214, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32162015

RESUMO

Herein, we report a rapid and sensitive colorimetric detection of Hg2+ by designing a specific DNA probe with phosphorothioate RNA modification (PS-probe) for Hg2+ recognition and utilizing DNA-modified gold nanoparticles (DNA-AuNPs) as the transducer. The distance between two DNA-AuNPs is controlled by a linker DNA, providing the linker DNA-regulated aggregation or dispersion status of AuNPs in solution. Exonuclease III (Exo III) can trigger the recycled digestion of linker DNA strands, inhibiting the reformation of aggregated nanoparticles and hence leading to a color shift from purple to red. However, the Hg2+-induced cleavage of the PS-probe can efficiently prevent the digestion of linker DNA strands by Exo III and hence reassemble the modified AuNPs to form aggregates in purple color. Thus, a positive correlation between the linker DNA strands left and the addition of Hg2+ provides a quantitative basis for Hg2+ sensing. A linear range of A520/A700 versus Hg2+ concentration is achieved in the range 2-100 nM associated with a detection limit as low as 1.30 ± 0.04 nM. Moreover, the biosensor exhibits excellent selectivity for Hg2+. The strong selectivity behavior was confirmed by recoveries ranging from 96 to 114% in real water samples. Graphical abstractSchematic representation of sensing mechanism of Hg2+ using a DNA probe with phosphorothioate RNA modification (PS-probe) and Exo III-assisted signal amplification.

5.
Int J Mol Sci ; 21(5)2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32121400

RESUMO

Cotton fibres, as single cells arising from the seed coat, can be classified as lint and fuzz according to their final length. Gossypium arboreum is a cultivated diploid cotton species and a potential donor of the A subgenome of the more widely grown tetraploid cottons. In this study, we performed genetic studies on one lintless and seven fuzzless G. arboreum accessions. Through association and genetic linkage analyses, a recessive locus on Chr06 containing GaHD-1 was found to be the likely gene underlying the lintless trait. GaHD-1 carried a mutation at a splicing acceptor site that resulted in alternative splicing and a deletion of 247 amino acid from the protein. The regions containing GaGIR1 and GaMYB25-like were found to be associated with fuzz development in G. arboreum, with the former being the major contributor. Comparative transcriptome analyses using 0-5 days post-anthesis (dpa) ovules from lintless, fuzzless, and normal fuzzy seed G. arboreum accessions revealed gene modules and hub genes potentially important for lint and fuzz initiation and development. Three significant modules and 26 hub genes associated with lint fibre initiation were detected by weighted gene co-expression network analysis. Similar analyses identified three vital modules and 10 hub genes to be associated with fuzz development. The findings in this study contribute to understanding the complex molecular mechanism(s) regulating fibre initiation and development and indicate that G. arboreum may have fibre developmental pathways different from tetraploid cotton. It also provides candidate genes for further investigation into modifying fibre development in G. arboreum.

6.
Genome Biol ; 21(1): 70, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32213201

RESUMO

BACKGROUND: Worldwide feralization of crop species into agricultural weeds threatens global food security. Weedy rice is a feral form of rice that infests paddies worldwide and aggressively outcompetes cultivated varieties. Despite increasing attention in recent years, a comprehensive understanding of the origins of weedy crop relatives and how a universal feralization process acts at the genomic and molecular level to allow the rapid adaptation to weediness are still yet to be explored. RESULTS: We use whole-genome sequencing to examine the origin and adaptation of 524 global weedy rice samples representing all major regions of rice cultivation. Weed populations have evolved multiple times from cultivated rice, and a strikingly high proportion of contemporary Asian weed strains can be traced to a few Green Revolution cultivars that were widely grown in the late twentieth century. Latin American weedy rice stands out in having originated through extensive hybridization. Selection scans indicate that most genomic regions underlying weedy adaptations do not overlap with domestication targets of selection, suggesting that feralization occurs largely through changes at loci unrelated to domestication. CONCLUSIONS: This is the first investigation to provide detailed genomic characterizations of weedy rice on a global scale, and the results reveal diverse genetic mechanisms underlying worldwide convergent rice feralization.

7.
Fish Shellfish Immunol ; 100: 9-17, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32130975

RESUMO

Interleukin (IL)-11 is a multifunctional cytokine that exerts a series of important immunomodulatory effects and exists in many tissues and cells. A 1106-bp nucleotide sequence representing the complete cDNA of IL-11 was obtained from large yellow croaker (Larimichthys crocea), containing an open reading frame (ORF) of 603 bp encoding for 200 amino acids (aa). The predicted LcIL-11 protein included a 12aa signal peptide and a conserved IL-11 domain. The polypeptide sequence identities between LcIL-11 and its counterparts in mammals and other fish are from 84% to 92% with known fish IL-11a and 22%-27% with fish IL-11b. LcIL-11 mRNA existed in most tissues with the most predominant expression in the gill. After immune challenge, the expression levels of LcIL-11 were induced largely in vivo and in vitro, with the peak-value of 32 times as much as the control in the liver at 24 h after Vibrio parahaemolyticus injection (p < 0.05) and the greatest value of 13.9 times as much as the control in LCK cells at 12 h after poly I:C stimulation (p < 0.05). Furthermore, the overexpression vector pcDNA3.1-LcIL-11 was constructed and transfected to LCK cells. Our results showed that the transcriptional expression levels of tumor necrosis factor (TNF)-α and myxovirus resistant protein (Mx) significantly up-regulated in LCK cells after LcIL-11 overexpression (p < 0.05). However, no significant changes of IL-1ß, janus kinase (JAK)2 and signal transducers and activators of transcription (STAT)5 was detected. Our finding indicated that LcIL-11 might enhance TNF-α and antiviral protein Mx expression in large yellow croaker.

8.
Pharmazie ; 75(2): 94-101, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32213241

RESUMO

An octahedral Pt (IV) prodrug, Cis-wog, containing a wogonin derivative as a bioactive axial ligand was designed and prepared to suppress DDR (DNA damage repair)-related proteins. In vitro biological studies indicated that a Pt (IV) prodrug with axially functional groups (Cis-wog) showed cytotoxicity superior to cisplatin and reversed its resistance against two pairs of cisplatin sensitive and resistant cell lines. Further mechanistic research revealed that the powerful antitumor activity of Cis-wog resulted from its suppression of JWA and its multi-interaction with XRCC1 to repair DNA single strand breaks (SSBs) caused by the introduction of wogonin. It is concluded that Cis-wog is a promising cytotoxic agent, which could be used for enhancing the antitumor activity of its corresponding Pt(II)-based drugs and reversing cisplatin resistance via decaying JWA-mediated SSBs repair pathways and inducing apoptosis.

9.
Theranostics ; 10(5): 2358-2373, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104508

RESUMO

Invadopodia formation is a key driver of cancer metastasis. The noncanonical IkB-related kinase IKKε has been implicated in cancer metastasis, but its roles in invadopodia formation and colorectal cancer (CRC) metastasis are unclear. Methods: Immunofluorescence, gelatin-degradation assay, wound healing assay and transwell invasion assay were used to determine the influence of IKKε over-expression, knockdown and pharmacological inhibition on invadopodia formation and the migratory and invasive capacity of CRC cells in vitro. Effects of IKKε knockdown or pharmacological inhibition on CRC metastasis were examined in mice. Immunohistochemistry staining was used to detect expression levels of IKKε in CRC patient tissues, and its association with prognosis in CRC patients was also analyzed. Immunoprecipitation, western blotting and in vitro kinase assay were constructed to investigate the molecular mechanisms. Results: IKKε co-localizes with F-actin and the invadopodia marker Tks5 at the gelatin-degrading sites of CRC cells. Genetic over-expression/knockdown or pharmacological inhibition of IKKε altered invadopodia formation and the migratory and invasive capacity of CRC cells in vitro. In vivo, knockdown or pharmacological inhibition of IKKε significantly suppressed metastasis of CRC cells in mice. IKKε knockdown also inhibited invadopodia formation in vivo. Clinical investigation of tumor specimens from 191 patients with CRC revealed that high IKKε expression correlates with metastasis and poor prognosis of CRC. Mechanistically, IKKε directly binds to and phosphorylates kindlin-2 at serine 159; this effect mediates the IKKε-induced invadopodia formation and promotion of CRC metastasis. Conclusions: We identify IKKε as a novel regulator of invadopodia formation and a unique mechanism by which IKKε promotes the metastasis of CRC. Our study suggests that IKKε is a potential target to suppress CRC metastasis.

10.
FASEB J ; 34(3): 4591-4601, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32017279

RESUMO

Injury of renal tubular epithelial cells is a key feature of the pathogenicity associated with tubulointerstitial fibrosis and other kidney diseases. HUWE1, an E3 ubiquitin ligase, acts by participating in ubiquitination and degradation of its target proteins. However, the detailed mechanisms by which HUWE1 might regulate fibrosis in renal tubular epithelial cells have not been established. Here, the possible regulation of renal tubulointerstitial fibrosis by HUWE1 was investigated by examining the expression of HUWE1 and EGFR in unilateral ureteral obstruction (UUO) mice. Markedly consistent reciprocal changes in HUWE1 and EGFR expression were observed at the protein and mRNA levels in the kidney after UUO injury. Expression of HUWE1 inhibited TGF-ß-induced injury to HK-2 cells, while HUWE1 overexpression decreased the expression of EGFR. Further analysis indicated that HUWE1 physically interacted with EGFR and promoted its ubiquitination and degradation. HUWE1 expression also showed clinical relevance in renal disease, as it notably decreased in multiple types of clinical nephropathy, while EGFR expression significantly increased when compared to the normal kidney. Therefore, this study demonstrated that HUWE1, which serves as an E3 ubiquitin ligase specific for EGFR, promotes EGFR ubiquitination and degradation, thereby regulating EGFR expression and providing protection against kidney injury.

11.
Bioresour Technol ; 303: 122958, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32058911

RESUMO

A coupled microbial electrolysis cell - anaerobic granular sludge system (MEC-AGS) was established to explore the degradation efficiency of 2,4,6-trichlorophenol (TCP) with synchronous biogas production. Results showed that MEC-AGS yielded a higher proportion of CH4 than MEC (83.8 ± 0.4% vs 82.0 ± 1.0%, P < 0.05) with sodium acetate (NaAc) as the only carbon source. Moreover, MEC-AGS had higher tolerance to the addition of TCP, with the highest TCP degradation efficiency of 45.5 ± 0.5% under 5 mg L-1 of TCP addition in 24 h. Furthermore, microbial community structures were significantly changed based on community composition, hierarchical cluster and PCoA analysis, which proved that MEC-AGS favored the enrichment of dechlorination-related microbes such as Pseudomonas, Desulfovibrio and Longilinea, as well as their syntrophic bacteria of Anaerolineacea, Syntrophobacter, Arcobacter, etc. The coupled system provides a promising strategy for biogas production from wastewater with recalcitrant organics.


Assuntos
Biocombustíveis , Esgotos , Anaerobiose , Reatores Biológicos , Clorofenóis , Eletrólise
12.
Cell Death Dis ; 11(2): 146, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094322

RESUMO

Renal fibrosis arises by the generation of matrix-producing fibroblasts and myofibroblasts through the epithelial-mesenchymal transition (EMT), a process in which epithelial cells undergo a transition into a fibroblast phenotype. A key feature of the EMT is the reorganization of the cytoskeletons, which may involve the Ca2+-binding protein S100A16, a newly reported member of the S100 protein family. However, very few studies have examined the role of S100A16 in renal tubulointerstitial fibrosis. In this study, S100A16 expression was examined by immunohistochemical staining of kidney biopsy specimens from patients with various nephropathies and kidney tissues from a unilateral ureteral obstruction (UUO) mouse model. Renal histological changes were investigated in S100A16Tg, S100A16+/-, and WT mouse kidneys after UUO. The expression of epithelia marker E-cadherin, mesenchymal markers N-cadherin, and vimentin, extracellular matrix protein, and S100A16, as well as the organization of F-actin, were investigated in S100A16 overexpression or knockdown HK-2 cells. Mass spectrometry was employed to screen for S100A16 binding proteins in HK-2 cells. The results indicated that S100A16 is high expressed and associated with renal tubulointerstitial fibrosis in patient kidney biopsies and in those from UUO mice. S100A16 promotes renal interstitial fibrosis in UUO mice. S100A16 expression responded to increasing Ca2+ and interacted with myosin-9 during kidney injury or TGF-ß stimulation to promote cytoskeleton reorganization and EMT progression in renal tubulointerstitial fibrosis. Therefore, S100A16 is a critical regulator of renal tubulointerstitial fibroblast activation and is therefore a potential therapeutic target for the treatment of renal fibrosis.

13.
Fitoterapia ; : 104494, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32045693

RESUMO

Two new phthalideisoquinoline hemiacetal alkaloid derivatives, named corybensines A and B (1 and 2), and four known alkaloids (3-6) were isolated from the bulbs of Corydalis decumbens. Their structures were characterized by analysis of 1D/2D NMR and ECD data, quantum chemical ECD calculations, and by X-ray diffraction analysis. Among them, compound 2 represents the first naturally occurring phthalideisoquinoline hemiacetal alkaloid derivative with a 2-pyrrolidinone moiety. The activity of the isolated compounds towards neuronal excitability was examined.

14.
Theranostics ; 10(4): 1758-1776, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32042335

RESUMO

Background and Aim: DOT1L regulates various genes involved in cancer onset and progression by catalyzing H3K79 methylation, but how DOT1L activity itself is regulated is unclear. Here, we aimed to identify specific DOT1L post-translational modifications that might regulate DOT1L activity and thus impact on colorectal cancer (CRC) progression. Methods: We conducted affinity purification and mass spectrometry to explore DOT1L post-translational modifications. We then established transwell migration and invasion assays to specifically investigate the role of DOT1L(K358) acetylation on CRC cellular behavior in vitro and a bioluminescence imaging approach to determine the role of DOT1L(K358) acetylation in CRC metastasis in vivo. We performed chromatin immunoprecipitation to identify DOT1L acetylation-controlled target genes. Finally, we used immunohistochemical staining of human tissue arrays to examine the relevance of DOT1L(K358) acetylation in CRC progression and metastasis and the correlation between DOT1L acetylation and CBP. Results: We found that CBP mediates DOT1L K358 acetylation in human colon cancer cells and positively correlates with CRC stages. Mechanistically, DOT1L acetylation confers DOT1L stability by preventing the binding of RNF8 to DOT1L and subsequent proteasomal degradation, but does not affect its enzyme activity. Once stabilized, DOT1L can catalyze the H3K79 methylation of genes involved in epithelial-mesenchymal transition, including SNAIL and ZEB1. An acetylation mimic DOT1L mutant (Q358) could induce a cancer-like phenotype in vitro, characterized by metastasis and invasion. Finally, DOT1L(K358) acetylation correlated with CRC progression and a poor survival rate as well as with high CBP expression. Conclusions: DOT1L acetylation by CBP drives CRC progression and metastasis. Targeting DOT1L deacetylation signaling is a potential therapeutic strategy for DOT1L-driven cancers.

15.
Genes (Basel) ; 11(2)2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32024145

RESUMO

Antimicrobial peptides (AMPs) are evolutionarily ancient molecules that play an essential role in innate immunity across taxa from invertebrates to vertebrates. The evolution system of AMP system has not been well explained in the literature. In this study, we cloned and sequenced AMP transcriptomes of three frog species, namely Rana dybowskii, Rana amurensis, and Pelophylax nigromaculatus, which are partially sympatric in northeast Asia, but show different habitat preferences. We found that each species contained 7 to 14 families of AMPs and the diversity was higher in species with a large geographic range and greater habitat variation. All AMPs are phylogenetically related but not associated with the speciation process. Most AMP genes were under negative selection. We propose that the diversification and addition of novel functions and improvement of antimicrobial efficiency are facilitated by the expansion of family members and numbers. We also documented significant negative correlation of net charges and numbers of amino acid residues between the propiece and mature peptide segments. This supports the Net Charge Balance Hypothesis. We propose the Cut Point Sliding Hypothesis as a novel diversification mechanism to explain the correlation in lengths of the two segments.

16.
Medicine (Baltimore) ; 99(7): e19243, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049865

RESUMO

D-dimer level is a direct measure of activated coagulation and has been used as a biomarker of hypercoagulability. In this study, we aimed to explore the associations between D-dimer level and the clinicopathological features and prognosis in metastatic colorectal cancer (mCRC) patients. One hundred seventy-eight patients diagnosed with mCRC from the Department of General Surgery, Jingmen First People's Hospital from September 2014 to December 2018 were collected. Data of coagulation index was evaluated and survival analysis was performed to identify the biomarker of mCRC. Among 178 cases of colorectal cancer, we found that the value of 0.55 mg/L, 5ng/ml and 40U/ml were cut-off values of D-Dimer, CEA and CA-199 for patients survival, respectively. hypercoagulability was much more frequent in patients aged ≥60 years than <60 years (P < .001) and also in patients with ECOG ≥2 points (P < .001). Moreover, those patients who have CEA >5ng/ml and CA-199>40U/ml had hypercoagulable state (P < .001). There was a significant difference in D-Dimer >0.55 mg/L and D-Dimer ≤0.55 mg/L among the number of metastatic sites (P < .01) and patients with comorbidities (P < .01). Survival analysis showed that patients with D-Dimer >0.55 mg/L have significantly unfavorable overall survival (P = .006) and progressive free survival (P = .011).


Assuntos
Neoplasias Colorretais/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , China/epidemiologia , Estudos de Coortes , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Trombofilia
17.
J Hematol Oncol ; 13(1): 2, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900208

RESUMO

BACKGROUND: Clinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6-12 months and a 5-year survival rate of less than 20%. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear. METHODS: AGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase reporter assays, immunofluorescence and in vivo experiments. RESULTS: AGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3ß signalling pathway in RCC, AGK can increase nuclear accumulation of ß-catenin, which further upregulated TCF/LEF transcription factor activity. CONCLUSIONS: AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3ß signalling pathway and might be a potential target for the further research of RCC.

18.
Inorg Chem ; 59(2): 1323-1331, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31920084

RESUMO

We first design and synthesize a dendritic aromatic 6-carboxyl linker (H6TDCPB), which is successfully assembled with Cd(II) ion to construct a porous metal-organic framework with a raw Cd6 cluster, {[Cd3(TDCPB)·2DMAc]·DMAc·4H2O}n (namely, complex 1). More interestingly, six adjacent linkers are packed together by π-π-stacking interactions to form an amazing six-molecule accumulation in the crystal structure. By virtue of high stability and luminescent properties, the as-synthesized sample not merely owns an excellent detectable ability but also possesses an outstanding selectivity for nitrofurans with remarkable recursitivity.


Assuntos
Antibacterianos/análise , Corantes Fluorescentes/química , Medições Luminescentes , Estruturas Metalorgânicas/química , Corantes Fluorescentes/síntese química , Estruturas Metalorgânicas/síntese química , Estrutura Molecular
19.
J Colloid Interface Sci ; 565: 177-185, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31958657

RESUMO

Non-noble-metal-based catalysts for catalyzing the oxidative coupling of aldehydes and ammonia represent an efficient atom-economical synthetic route to produce nitriles. In this study, an effective Fe-modified N-doped carbon catalyst anchored on fibrous silica nanospheres (Fe-N/KCC-1-T) was successfully prepared by a facile strategy. 1,10-Phenanthroline with a strong chelating ability ensured the homogeneous, ultrafine distribution of Fe-based active sites, and the KCC-1 support material effectively enhanced the accessibility to these active sites, which corresponded to center-radial pore channels and a high surface area. As-fabricated Fe-N/KCC-1-T exhibited excellent catalytic performance for the ammoxidation of aldehydes under mild reaction conditions. A series of functionalized aldehydes were efficiently oxidized into the corresponding nitriles by using air as the green oxidant. Moreover, the catalyst was recycled for at least five runs without any clear decrease in the performance. Hence, this study is expected to provide an eco-friendly synthetic route to produce nitriles from easily available aldehydes and ammonia by using a cost-effective catalyst.

20.
BMJ Open ; 10(1): e032379, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31915163

RESUMO

INTRODUCTION: Perioperative infections may be considered predictors of caesarean scar defect (CSD), and multidose antibiotics have a protective effect against CSD. However, the ability of adjunctive azithromycin combined with cephalosporin to reduce the prevalence of CSD remains unclear. The planned study aims to clarify the protective effect of antibiotics against CSD and to assess the effectiveness of adjunctive azithromycin prophylaxis for CSD. METHODS AND ANALYSIS: This study is a double-blind, parallel-control randomised clinical trial that will be carried out at the International Peace Maternity and Child Health Hospital. A total of 220 eligible patients will be randomised (1:1) to receive either adjunctive azithromycin or single-dose cephalosporin 30 min before the incision. The evaluation criteria are the prevalence and characteristics of CSD as assessed by transvaginal ultrasound (TVU) and saline infusion sonohysterography (SIS) at 42 days, 6 months and 12 months after delivery. The primary outcome will be the prevalence of CSD, and the characteristics of CSD will be assessed by TVU and SIS 42 days after delivery; all other outcomes are secondary. ETHICS AND DISSEMINATION: This protocol received authorisation from the Medical Research Ethics Committee of International Peace Maternity and Child Health Hospital on 25 April 2018 (approval no. GKLW2017-84). The findings will be reported in peer-reviewed publications and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: ChiCTR-INR-17013272.

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