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1.
Am J Med Sci ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34998723

RESUMO

BACKGROUND: Endoscopic ultrasound (EUS) is widely used as a cost-effective method for detecting pancreatic neuroendocrine tumors (PNTs), but its diagnostic value is variable among published studies. This meta-analysis aimed to determine the diagnostic value of EUS for PNTs. METHODS: Three electronic databases, including PubMed, Embase, and the Cochrane Library, were searched for studies published up to July 2018. The summary sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and receiver operating characteristic (ROC) curve were calculated to evaluate the diagnostic value of EUS using the random-effects model. RESULTS: Thirteen studies involving 609 patients were included in this meta-analysis. The summary sensitivity and specificity of EUS for detecting PNTs were 0.86 and 0.89, respectively. The PLR and NLR of EUS were 7.81 and 0.15, respectively. The DOR of EUS for diagnosing PNTs was 24.20. The area under the ROC was 0.90. Finally, the subgroup analyses indicated that publication year and percentage of males could introduce potential biases for the DOR of EUS. CONCLUSIONS: This meta-analysis suggests that EUS has a relatively high diagnostic value for diagnosing PNTs.

2.
Cancer Lett ; 527: 164-173, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34952145

RESUMO

As the downstream effectors of Hippo pathway, YAP/TAZ are identified to participate in organ growth, regeneration and tumorigenesis. However, owing to lack of a DNA-binding domain, YAP/TAZ usually act as coactivators and cooperate with other transcription factors or partners to mediate their transcriptional outputs. In this article, we first present an overview of the core components and the upstream regulators of Hippo-YAP/TAZ signaling in mammals, and then systematically summarize the identified transcription factors or partners that are responsible for the downstream transcriptional output of YAP/TAZ in various cancers.

4.
Biomed Res Int ; 2021: 1004849, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34901265

RESUMO

Objective: This current research is aimed at assessing clinical efficacy and prognosis of three-dimensional (3D) printing assisted patient-specific instrument (PSI) osteotomy guide in precise osteotomy of adult talipes equinovarus (ATE). Methods: We included a total of 27 patients of ATE malformation (including 12 males and 15 females) from June 2014 to June 2018 in the current research. The patients were divided into the routine group (n = 12) and 3D printing group (n = 15) based on different operative methods. The parameters, including the operative time, intraoperative blood loss, complications, time to obtain bony fusion, functional outcomes based on American Orthopedic Foot and Ankle Society (AOFAS), and International Congenital Clubfoot Study group (ICFSG) scoring systems between the two groups were observed and recorded regularly. Results: The 3D printing group exhibits superiorities in shorter operative time, less intraoperative blood loss, higher rate of excellent, and good outcomes presented by ICFSG score at last follow-up (P < 0.001, P < 0.001, P = 0.019) than the routine group. However, there was no significant difference exhibited in the AOFAS score at the last follow-up and total rate of complications between the two groups (P = 0.136, P = 0.291). Conclusion: Operation assisted by 3D printing PSI osteotomy guide for correcting the ATE malformation is novel and feasible, which might be an effective method to polish up the precise osteotomy of ATE malformation and enhance the clinical efficacy.


Assuntos
Osteotomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Sangue Operatório/efeitos adversos , Duração da Cirurgia , Impressão Tridimensional , Estudos Retrospectivos , Resultado do Tratamento
5.
Genes (Basel) ; 12(11)2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34828353

RESUMO

The N6-methyladenosine (m6A) RNA modification can regulate autophagy to modulate the growth and development of tumors, but the mechanism of m6A modification for the regulation of autophagy in hepatocellular carcinoma cells (HCC) remains unclear. In the study, the knockdown of the Wilms' tumor 1-associating protein (WTAP) was made in HCC to study the correlation between m6A modification and autophagy. A fluorescent confocal microscopy analysis showed that the knockdown of WTAP could facilitate the autophagy of HCC. A Western blot analysis showed that the level of p-AMPK was decreased in WTAP-knockdown HCC cells. Additionally, LKB1, the upstream kinase of AMPK, was regulated by WTAP and it could mediate the phosphorylation of AMPK in an m6A-dependent manner. Further studies revealed that the knockdown of WTAP could reduce the level of LKB1 mRNA with m6A. This could result in the increased stability of LKB1 mRNA to promote its expression. The knockdown of WTAP could upregulate the level of autophagy and inhibit HCC proliferation. However, the overexpression of WTAP could resist autophagic cell death.

6.
Front Oncol ; 11: 718871, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778033

RESUMO

Background: BRCA2 mutation has a more substantial impact on the homologous recombination and superior therapeutic response to platinum-based chemotherapy than BRCA1 mutation. Whether BRCA2-mutated patients could benefit more from PARPi than BRCA1-mutated patients remains unclear. We performed a meta-analysis to assess the efficacy difference of PARPi between BRCA1 mutation carriers and BRCA2 mutation carriers. Methods: Pubmed, Embase, and Cochrane Library were comprehensively searched for randomized controlled trials (RCTs) of PARPi that had available hazard ratios (HRs) of progression-free survival (PFS) in both BRCA1-mutated population and BRCA2-mutated population. We calculated the pooled PFS HRs and 95%CI using randomized-effect models, and the difference between the two estimates was compared by interaction test. Results: A total of 11 eligible RCTs of high quality were identified through search. Overall, 1544 BRCA1 mutation carriers and 1191 BRCA2 mutation carriers were included in the final analysis. The pooled PFS HR was 0.42 (95% CI: 0.35-0.50) in BRCA1-mutated patients who were treated with PARPi compared with patients in the control group. In BRCA2-mutated patients treated with PARPi, the pooled PFS HR compared with the control groups was 0.35 (95% CI: 0.24-0.51). The difference in efficacy of PARPi was not significant between the two subgroups (P heterogeneity = 0.40, for interaction). Conclusion: BRCA1-mutated patients and BRCA2-mutated patients could benefit from PARPi, and the efficacy is comparable. Currently, there is no evidence that BRCA2-mutated patients would benefit more from PARPi than BRCA1-mutated patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020214582.

7.
Chemosphere ; : 132907, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34780744

RESUMO

The aggregation of anaerobic ammonium oxidation (anammox) bacteria is important for the start-up and biomass retention of anammox processes. However, it is unclear whether it is beneficial to the activity, growth and reproduction of anammox bacteria. In this study, four reactor systems were developed to explore the effects of aggregation on anammox activity, growth and reproduction, after excluding the contribution of aggregation to sludge settling and retention. Results demonstrated that (i) compared with free-living planktonic bacteria, the aggregated bacteria had a higher volumetric nitrogen removal rate (0.75 kg-N/(m³·d)) and specific nitrogen removal activity (1.097 kg-N/VSS/d). And after 67 days cultivation, it had the higher sludge concentration and relative abundance (92.4%); (ii) compared with acidic polysaccharides and α-d-glucopyranose polysaccharides, ß-d-glucopyranose polysaccharide play more essential roles of anammox aggregation; (iii) norspermidine triggered the secretion of α-d-glucopyranose polysaccharides to combat the toxicity, and inhibited biomass growth rate; (iv) immobilization in polyvinyl alcohol (10%) or sodium alginate (2%) gel beads was better than sodium alginate-chitosan gel beads and norspermidine (biofilm inhibitor) for the cultivation of free-living planktonic anammox bacteria. This is the first comparative study of three methods for cultivating free-living anammox bacteria. In conclusion, we found that the aggregation of anammox sludge not only facilitates biomass retention but also enhances the bioactivity, relative abundance, growth, and reproduction rate of anammox bacteria. The work is helpful to understand the formation of anammox granular sludge and contribute to the fast start-up and stable operation in anammox application.

8.
J Am Chem Soc ; 143(47): 19956-19965, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34792328

RESUMO

The wide usage of N-heterocyclic carbenes (NHCs) has raised the quest for their deuterated molecules. Effective synthesis method to obtain them, however, has remained elusive. We present here a catalytic method for the preparation of deuterated NHCs, namely, the catalytic hydrogen-deuterium exchange reaction between NHCs and deuterated benzene using a coordinatively unsaturated Ru NHC catalyst. The catalytic system enables selective deuteration of the C(sp3)-H bonds of the alkyl groups on N-substituents, as well as the sterically nonhindered C(sp2)-H bonds of NHCs as demonstrated by the preparation of 16 deuterium-labeled NHCs that have a deuteration ratio on specified sites higher than 90%. The gram-scale synthesis of deuterated IMes indicated the applicability of this catalytic method. Mechanistic studies revealed that the high regio-selectivity toward those C(sp3)-H bonds on NHCs originates from the regio-selectivity of cyclometalation reactions of coordinatively unsaturated Ru NHC species.

9.
Exp Ther Med ; 22(5): 1275, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34594412

RESUMO

Oxidized low-density lipoprotein (ox-LDL) induces endothelial cell apoptosis and dysfunction. Statins are drugs that are clinically used to lower serum cholesterol levels, and they have been shown to exert vascular protective effects. In the present study, human umbilical vein endothelial cells were transfected with scramble control siRNA or siRNA specific for glutathione peroxidase (GPx)4 or cystine-glutamate antiporter (xCT). MTT, Matrigel and Transwell assays were used to evaluate cell proliferation, tube formation and migration, respectively. The levels of TNF-α, IL-α, 4-hydroxynonenal, GPx4 and xCT expression were detected by western blot analysis. It was demonstrated that ox-LDL promoted cytokine production and reduced the proliferation, migration and angiogenesis of endothelial cells. It was also observed that ox-LDL decreased GPx4 and xCT expression and induced ferroptosis. Furthermore, the inhibition of ferroptosis by deferoxamine mesylate attenuated ox-LDL-induced endothelial cell dysfunction and restored ox-LDL-decreased GPx4 and xCT expression. Consistent with these results, GPx4 and xCT knockdown by siRNA transfection aggravated ox-LDL-induced endothelial cell dysfunction and inhibition of proliferation. To the best of our knowledge, the present study was the first to discover that fluvastatin may protect endothelial cells from ox-LDL-induced ferroptosis and dysfunction. Furthermore, knockdown of GPx4 and xCT expression blunted the protective effects of fluvastatin on ox-LDL-treated endothelial cells. These data indicated a novel function of fluvastatin in the protection of endothelial cells from ox-LDL-induced ferroptosis, the mechanism of which involves the regulation of GPx4 and xCT.

10.
J Immunother Cancer ; 9(9)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34593618

RESUMO

BACKGROUND: Viral-based immunotherapy can overcome resistance to immune checkpoint blockade (ICB) and fill the unmet needs of many patients with cancer. Oncolytic viruses (OVs) are defined as engineered or naturally occurring viruses that selectively replicate in and kill cancer cells. OVs also induce antitumor immunity. The purpose of this study was to compare the antitumor effects of live oncolytic vaccinia viruses versus the inactivated versions and elucidate their underlying immunological mechanisms. METHODS: We engineered a replication-competent, oncolytic vaccinia virus (OV-GM) by inserting a murine GM-CSF gene into the thymidine kinase locus of a mutant vaccinia E3L∆83N, which lacks the Z-DNA-binding domain of vaccinia virulence factor E3. We compared the antitumor effects of intratumoral (IT) delivery of live OV-GM versus heat-inactivated OV-GM (heat-iOV-GM) in a murine B16-F10 melanoma bilateral implantation model. We also generated vvDD, a well-studied oncolytic vaccinia virus, and compared the antitumor effects of live vvDD vs heat-inactivated vvDD (heat-ivvDD) in a murine A20 B-cell lymphoma bilateral tumor implantation model. RESULTS: Heat-iOV-GM infection of dendritic cells (DCs) and tumor cells in vitro induced type I interferon and proinflammatory cytokines and chemokines, whereas live OV-GM did not. IT live OV-GM was less effective in generating systemic antitumor immunity compared with heat-iOV-GM. Similar to heat-iOV-GM, the antitumor effects of live OV-GM also require Batf3-dependent CD103+ dendritic cells. When combined with systemic delivery of ICB, IT heat-iOV-GM was more effective in eradicating tumors, compared with live OV-GM. IT heat-ivvDD was also more effective in treating murine A20 B-cell lymphoma, compared with live vvDD. CONCLUSIONS: Tumor lysis induced by the replication of oncolytic vaccinia virus has a limited effect on the generation of systemic antitumor immunity. The activation of Batf3-dependent CD103+ DCs is critical for antitumor effects induced by both live OV-GM and heat-iOV-GM, with the latter being more potent than live OV-GM in inducing innate and adaptive immunity in both locally injected and distant, non-injected tumors. We propose that evaluations of both innate and adaptive immunity, induced by IT oncolytic viral immunotherapy at injected and non-injected tumors, should be included as potential biomarkers for host responses to viral therapy.

11.
Clin Neurol Neurosurg ; 209: 106912, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34509141

RESUMO

BACKGROUND: To evaluate the value of serum Lactate Dehydrogenase (LDH) level in predicting recurrence and the overall survival (OS) of glioma patients. MATERIALS AND METHODS: A total number of 216 patients with glioma in our institution were retrospectively recruited to analyze the relationship between preoperative serum LDH level and prognosis. RESULTS: Overall, the median age of patients was 46.0 (31.0-57.0) years old; 53.7% (116 of 216) of the enrolled patients were male. Multivariate analysis revealed that serum LDH level (odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.96-0.98, P < 0.001) and World Health Organization (WHO) grade (grade II: OR = 19.64, 95%CI = 5.56-69.35, P < 0.001; grade III: OR =1 9.50, 95%CI = 7.08-53.73, P < 0.001; grade IV: OR = 15.23, 95%CI = 4.94-46.97, P < 0.001) were significant and independent of 1-year Progression-free survival (PFS) after adjusting for confounders. The predictive performance of serum LDH level was represented with area under curve (AUC) = 0.741, 95%CI = 0.677-0.798. Multivariate Cox analysis revealed that LDH level (hazard ratio [HR] = 2.56, 95%CI = 1.59-4.15, P < 0.001) and WHO grade (grade II: HR = 4.58, 95%CI = 0.56-37.23, P = 0.155; grade III: HR = 16.35, 95%CI = 2.16-123.80, P = 0.007; grade IV: HR = 42.13, 95%CI = 5.83-304.47, P < 0.001) remained associated with survival at 2-year follow-up. At 3-year follow-up, lymphocyte count (HR = 0.68, 95%CI = 0.51-0.91, P = 0.008), LDH level (HR = 2.21, 95%CI = 1.40-3.49, P = 0.001), and WHO grade (grade II: HR = 1.44, 95%CI = 0.44-4.68, P = 0.543; grade III: HR = 4.99, 95%CI = 1.68-14.87, P = 0.004; grade IV: HR = 16.96, 95%CI = 6.13-46.93, P < 0.001) remained associated with survival in multivariate Cox analysis. CONCLUSION: Our study demonstrated that preoperative serum LDH level could serve as a reliable indicator for predicting prognosis of glioma patients. Further multicenter studies are still required to verify our findings.

12.
Front Neurol ; 12: 711468, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512523

RESUMO

Objective: Early identification for the need of tracheostomy (TT) in aneurysmal subarachnoid hemorrhage (aSAH) patients remains one of the main challenges in clinical practice. Our study aimed to establish and validate a nomogram model for predicting postoperative TT in aSAH patients. Methods: Patients with aSAH receiving active treatment (interventional embolization or clipping) in our institution between June 2012 and December 2018 were retrospectively included. The effects of patients' baseline information, aneurysm features, and surgical factors on the occurrence of postoperative TT were investigated for establishing a nomogram in the training cohort with 393 patients. External validation for the nomogram was performed in the validation cohort with 242 patients. Results: After multivariate analysis, higher age, high neutrophil-to-lymphocyte ratio (NLR), high World Federation of Neurological Surgeons Scale (WFNS), and high Barrow Neurological Institute (BNI) grade were left in the final logistic regression model. The predictive power of the model was excellent in both training cohort and validation cohort [area under the curve (AUC): 0.924, 95% confidence interval [CI]: 0.893-0.948; AUC: 0.881, 95% CI: 0.833-0.919]. A nomogram consisting of these factors had a C-index of 0.924 (95% CI: 0.869-0.979) in the training cohort and was validated in the validation cohort (C-index: 0.881, 95% CI: 0.812-0.950). The calibration curves suggested good match between prediction and observation in both training and validation cohorts. Conclusion: Our study established and validated a nomogram model for predicting postoperative TT in aSAH patients.

13.
Front Microbiol ; 12: 715709, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497595

RESUMO

Silage is fed to horses in China and other areas in the world, however, knowledge about the impact of feeding silage on horse health is still limited. In the current study, 12 horses were assigned into two groups and fed ryegrass silage and ryegrass hay, respectively, for 8 weeks. High-throughput sequencing was applied to analyze fecal microbiota, while liquid chromatography-tandem mass spectrometry (LC-MS/MS) based metabolomics technique was used for blood metabolite profile to investigate the influence of feeding ryegrass silage (group S) compared to feeding ryegrass hay (group H) on equine intestinal and systemic health. Horses in group S had significantly different fecal microbiota and blood metabolomes from horses in group H. The results showed that Verrucomicrobia was significantly less abundant which plays important role in maintaining the mucus layer of the hindgut. Rikenellaceae and Christensenellaceae were markedly more abundant in group S and Rikenellaceae may be associated with some gut diseases and obesity. The metabolomics analysis demonstrated that ryegrass silage feeding significantly affected lipid metabolism and insulin resistance in horses, which might be associated with metabolic dysfunction. Furthermore, Pearson's correlation analysis revealed some correlations between bacterial taxa and blood metabolites, which added more evidence to diet-fecal microbiota-health relationship. Overall, ryegrass silage feeding impacted systemic metabolic pathways in horses, especially lipid metabolism. This study provides evidence of effects of feeding ryegrass silage on horses, which may affect fat metabolism and potentially increase risk of insulin resistance. Further investigation will be promoted to provide insight into the relationship of a silage-based diet and equine health.

14.
Front Endocrinol (Lausanne) ; 12: 719920, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539572

RESUMO

Observational studies report some association between circulating bilirubin levels and osteoporosis, but it is unknown if this association is causal or confounded. In this two-sample Mendelian randomization (MR) study, we included a large genome-wide association study (GWAS) associated with total bilirubin levels among 317,639 people, a large meta-analysis to identify genetic variants associated with bone mineral density (BMD) estimated by heel quantitative ultrasound (eBMD) among 426,824 individuals and fracture among 1.2 million individuals. The results revealed that circulating bilirubin levels had no causal influence on eBMD (beta-estimate: 0.004, 95% confidence interval [CI]: -0.019 to 0.028, SE:0.012, P-value=0.705) or the risk of fracture (beta-estimate: -0.009, 95% CI: -0.035 to 0.017, SE:0.013, P-value=0.488), which were both confirmed by multiple sensitivity analyses. Our results confirm that circulating bilirubin levels have no causal role in eBMD or the incidence of fracture, indicating that circulating bilirubin levels is unlikely to be a causal risk factor for osteoporosis or fracture.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34554920

RESUMO

Recently, extensive studies have focused on analyzing aerodynamic performance due to its important impact on aircraft design. Most of these works compute the aerodynamic coefficient of the airfoil through computational fluid dynamics (CFD) simulation, which is too time-consuming. To reduce the computational time required, some intelligence-based methods have been presented. However, these methods also suffer from certain issues. First, most of them directly implement existing machine learning methods used to predict the aerodynamic coefficient without adding any improvements. Second, some methods convert the airfoil shape and aerodynamic curves into images, which may lead to curve distortion and the introduction of noise. Third, some methods learn the relationship between the airfoil shape and aerodynamic coefficients but ignore the influence of initial inflow conditions. Accordingly, to address these issues, we propose an intelligent method for predicting the pressure coefficients (Cp) of airfoil based on a conditional generative adversarial network (cGAN). More specifically, we first present a two-step data augmentation strategy designed to expand the original airfoil dataset. Subsequently, we design a novel cGAN-based neural network to predict the Cp curve. To the best of our knowledge, this is the first work to apply generative adversarial network (GAN) to aerodynamic coefficient prediction. Moreover, we design a new loss function to train our network. Extensive experimental results demonstrate that the Cp curve predicted by our method is very close to that generated via CFD simulation. More importantly, our method achieves a speedup close to 1000x compared with CFD simulation.

16.
J Am Chem Soc ; 143(32): 12847-12856, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34347477

RESUMO

Metal-catalyzed hydrosilylation of alkynes is an ideal atom-economic method to prepare vinylsilanes that are useful reagents in the organic synthesis and silicone industry. Although great success has been made in the preparation of ß-vinylsilanes by metal-catalyzed hydrosilylation reactions of alkynes, reported metal-catalyzed reactions for the synthesis of α-vinylsilanes suffer from narrow substrate scope and/or poor selectivity. Herein, we present selective Markovnikov hydrosilylation reactions of terminal alkynes with tertiary silanes using a dicobalt carbonyl N-heterocyclic carbene (NHC) complex [(IPr)2Co2(CO)6] (IPr = 1,3-di(2,6-diisopropylphenyl)imidazol-2-ylidene) as catalyst. This cobalt catalyst effects the hydrosilylation of both alkyl- and aryl-substituted terminal alkynes with a variety of tertiary silanes with good functional group compatibility, furnishing α-vinylsilanes with high yields and high α/ß selectivity. Mechanistic study revealed that the stoichiometric reactions of [(IPr)2Co2(CO)6] with PhC≡CH and HSiEt3 can furnish the dinuclear cobalt alkyne and mononuclear cobalt silyl complexes [(IPr)(CO)2Co(µ-η2:η2-HCCPh)Co(CO)3], [(IPr)(CO)2Co(µ-η2:η2-HCCPh)Co(CO)2(IPr)], and [(IPr)Co(CO)3(SiEt3)], respectively. Both dicobalt bridging alkyne complexes can react with HSiEt3 to yield α-triethylsilyl styrene and effect the catalytic Markovnikov hydrosilylation reaction. However, the mono(NHC) dicobalt complex [(IPr)(CO)2Co(µ-η2:η2-HCCPh)Co(CO)3] exhibits higher catalytic activity over the di(NHC)-dicobalt complexes. The cobalt silyl complex [(IPr)Co(CO)3(SiEt3)] is ineffective in catalyzing the hydrosilylation reaction. Deuterium labeling experiments with PhC≡CD and DSiEt3 indicates the syn-addition nature of the hydrosilylation reaction. The absence of deuterium scrambling in the hydrosilylation products formed from the catalytic reaction of PhC≡CH with a mixture of DSiEt3 and HSi(OEt)3 hints that mononuclear cobalt species are less likely the in-cycle species. These observations, in addition to the evident of nonsymmetric Co2C2-butterfly core in the structure of [(IPr)(CO)2Co(µ-η2:η2-HCCPh)Co(CO)3], point out that mono(IPr)-dicobalt species are the genuine catalysts for the cobalt-catalyzed hydrosilylation reaction and that the high α selectivity of the catalytic system originates from the joint play of the dicobalt carbonyl species to coordinate alkynes in the Co(µ-η2:η2-HCCR')Co mode and the steric demanding nature of IPr ligand.

17.
J Am Chem Soc ; 143(28): 10751-10759, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34232039

RESUMO

Mononuclear Pd(I) species are putative intermediates in Pd-catalyzed reactions, but our knowledge about them is limited due to difficulties in accessing them. Herein, we report the isolation of a Pd(I) amido complex, [(BINAP)Pd(NHArTrip)] (BINAP = 2,2'-bis(diphenylphosphino)-1,1'-binaphthalene, ArTrip = 2,6-bis(2',4',6'-triisopropylphenyl)phenyl), from the reaction of (BINAP)PdCl2 with LiNHArTrip. This Pd(I) amido species has been characterized by X-ray crystallography, electron paramagnetic resonance, and multiedge Pd X-ray absorption spectroscopy. Theoretical study revealed that, while the three-electron-two-center π-interaction between Pd and N in the Pd(I) complex imposes severe Pauli repulsion in its Pd-N bond, pronounced attractive interligand dispersion force aids its stabilization. In accord with its electronic features, reactions of homolytic Pd-N bond cleavage and deprotonation of primary amines are observed on the Pd(I) amido complex.

18.
Neoplasia ; 23(8): 766-774, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34233230

RESUMO

Death receptor 4 (DR4) is a cell surface protein that is generally thought to mediate apoptosis upon binding to its ligand named TRAIL. However, its contribution to apoptosis resistance has also been reported. MET (or c-MET) gene amplification represents an important mechanism for acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) against EGFR mutant non-small cell lung cancer (NSCLC). This study focuses on demonstrating the impact of MET inhibition on DR4 modulation in MET-amplified EGFR mutant NSCLC cell lines and the underlying mechanisms. Several MET inhibitors decreased DR4 levels in MET-amplified HCC827 cell lines resistant to EGFR-TKIs with no or limited effects on modulating DR5 levels, while increasing DR4 levels in HCC827 parental cells and other NSCLC cell lines. MET inhibitors did not affect DR4 stability, but decreased DR4 mRNA levels with suppression of AP-1-dependent DR4 promoter transactivation. Moreover, these inhibitors suppressed ERK and c-Jun phosphorylation accompanied with decreasing c-Jun levels. Hence, it is likely that MET inhibition downregulates DR4 expression in MET-amplified EGFR mutant NSCLC cells through suppressing AP-1-mediated DR4 transcription. Osimertinib combined with MET inhibition synergistically induces apoptosis in the MET-amplified EGFR mutant NSCLC cells accompanied with augmented DR4 reduction both in vitro and in vivo. Furthermore, MET inhibition combined with TRAIL enhanced killing of MET-amplified EGFR mutant HCC827/AR cells, but not HCC827 parental cells. These data collectively suggest that DR4 may possess an unrecognized anti-apoptotic function, contributing to apoptosis resistance under given conditions.

20.
Animals (Basel) ; 11(5)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34066969

RESUMO

Diet is an important factor affecting intestinal microbiota in horses. Fecal microbiota is commonly used as a substitute for studying hindgut microbiota when investigating the relationship between intestinal microbial changes and host health. So far, no study has compared the difference between the fecal microbiota found in horses that are fed pasture grass, silage, and hay. The present study aims to characterize the fecal microbiota in horses that were exclusively on one of the three forage diets, and to analyze the potential impact of these forages, especially silage, on horse intestinal health. There were 36 horses randomly assigned to each of the three groups; each group was fed only one type of forage for 8 weeks. High throughput sequencing was applied to analyze the bacterial taxa in fecal samples collected from the horses at the end of the feeding trial. The Lachnospiraceae family was statistically more abundant in horses fed with hay, while it was the least abundant in horses fed with silage. The Streptococcaceae spp., considered a core microbial component in equine intestinal microbiota, were present in significantly lower quantities in feces from horses that were fed pasture grass as compared to those from horses fed hay or silage. The novel data may help promote the balancing of horse intestinal microbiota and the maintenance of intestinal health in horses.

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