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1.
Cancer Biomark ; 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34151833

RESUMO

This paper aimed at investigating AS1 expression in prostate cancer (PCa) and its effects on the proliferation and invasion of prostate cancer cells (PCCs). The prostate tissues and the matched adjacent normal prostate tissues excised and preserved during radical prostatectomy in our hospital were collected. The LncRNA NCK1-AS1 expression was detected. PCa patients were followed up for three years to analyze their prognosis. The correlation of LncRNA NCK1-AS1 expression with clinicopathological features was analyzed. Human normal prostate cells and human PCCs were selected, in which LncRNA NCK1-AS1 expression was tested to screen and then transfect the cells. Cell proliferation, invasion and migration were detected. Cell cycles and apoptosis were analyzed. Compared with the adjacent normal tissues, LncRNA NCK1-AS1 was highly expressed in the prostate cancer tissues. Its expression was remarkably different in those with different stages of TNM and with lymphatic metastasis or not. The prognosis of patients with high LncRNA NCK1-AS1 expression was remarkably poorer than that of those with low expression. Compared with the human normal prostate cells, LncRNA NCK1-AS1 expression in the human PCCs remarkably rose, with the greatest difference in 22Rv1 cells. Compared with the Blank group, cell proliferation and the number of plate cloned cells remarkably reduced in the sh-NCK1-AS1 group. Additionally, in this group, the number of invasive and migratory cells remarkably reduced; the expression of invasion-related protein E-cadherin remarkably rose but that of MMP-2 remarkably reduced; cell cycles were arrested and the expression of cycle-related proteins (CDK4, CDK6, cyclin D1) remarkably reduced; the apoptotic rate and the expression of apoptosis-related protein Bax remarkably rose. LncRNA NCK1-AS1 is highly expressed in PCa, so its down-regulation can inhibit PCCs from proliferating and reduce the number of invasive cells.

2.
J Hazard Mater ; 418: 126238, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34119976

RESUMO

Arsenite (As(III)) is more toxic and difficult to remove than arsenate (As(V)). In this study, an S-doped Cu-La bimetallic oxide (S-CuLaO) decorated with metal-organic framework (MOF) composite (S-CuLaO@UIO-66) was synthesized and applied for the adsorption of As(III). The maximum adsorption capacity of As(III) by S-CuLaO@UIO-66 was as high as 171 mg/g, which was much higher compared with other MOF compounds reported to date. The UIO-66 support improved the dispersion and reduced the size of the S-CuLaO particles, which increased the number of exposed adsorption reactive sites. Study of the mechanism revealed that the synchronous oxidation and adsorption significantly increased the removal of As(III). O2∙- was produced by the receiving electron from the dissolved oxygen from Cu(I) in S-CuLaO, which converted As(III) to As(V). Furthermore, the stability and reusability S-CuLaO@UIO-66 (without regeneration) was investigated at a low As(III) concentration (approximately 1000 µg/L) in deionized water and well water. The residual arsenic concentration ranged from 0.8 to 2.8 µg/L in deionized water and 3-58.2 µg/L in well water within 240 min during three cycles. Generally, this study suggests that combining an optimal oxide with a stable MOF is a promising approach for the fabrication of composite adsorbents.

3.
Inorg Chem ; 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061510

RESUMO

An open-frame aluminophosphate, K[(Zn0.5Al0.5)2P2O8] (KZAPO), was rationally designed by a substitution design strategy and synthesized by a high-temperature molten salt method. Compared with the parent crystal of K[ZnBP2O8], KZAPO was characterized by similar 4 × 8 × 8 networks, a comparable short-wave ultraviolet transparency and a more regular tetrahedral frame with the mixing of (ZnO4)6- and (AlO4)5- anionic groups, highlighting the multifunctional roles that anionic group mixing played in structural and property modulations. In particular, KZAPO was characterized by a high thermal stability (over 850 °C) and a congruent-melting behavior, being conducive to practical applications.

4.
Open Biol ; 11(6): 210020, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34062094

RESUMO

Smoothened is a key receptor of the hedgehog pathway, but the roles of Smoothened in cardiac development remain incompletely understood. In this study, we found that the conditional knockout of Smoothened from the mesoderm impaired the development of the venous pole of the heart and resulted in hypoplasia of the atrium/inflow tract (IFT) and a low heart rate. The blockage of Smoothened led to reduced expression of genes critical for sinoatrial node (SAN) development in the IFT. In a cardiac cell culture model, we identified a Gli2-Tbx5-Hcn4 pathway that controls SAN development. In the mutant embryos, the endocardial-to-mesenchymal transition (EndMT) in the atrioventricular cushion failed, and Bmp signalling was downregulated. The addition of Bmp2 rescued the EndMT in mutant explant cultures. Furthermore, we analysed Gli2+ scRNAseq and Tbx5-/- RNAseq data and explored the potential genes downstream of hedgehog signalling in posterior second heart field derivatives. In conclusion, our study reveals that Smoothened-mediated hedgehog signalling controls posterior cardiac progenitor commitment, which suggests that the mutation of Smoothened might be involved in the aetiology of congenital heart diseases related to the cardiac conduction system and heart valves.

5.
Anal Methods ; 13(20): 2320-2330, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-33960336

RESUMO

Here, we provide evidence that functionalizing the carbon-fiber surface with amines significantly improves direct electrochemical adenosine triphosphate (ATP) detection with fast-scan cyclic voltammetry (FSCV). ATP is an important extracellular signaling molecule throughout the body and can function as a neurotransmitter in the brain. Several methods have been developed over the years to monitor and quantitate ATP signaling in cells and tissues; however, many of them are limited in temporal resolution or are not capable of measuring ATP directly. FSCV at carbon-fiber microelectrodes is a widely used technique to measure neurotransmitters in real-time. Many electrode treatments have been developed to study the interaction of cationic compounds like dopamine at the carbon surface yet studies investigating how to improve anionic compounds, like ATP, at the carbon fiber surface are lacking. In this work, carbon-fibers were treated with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) which reacts with carboxylic acid groups on the carbon surface followed by reaction with ethylenediamine (EDA) to produce NH2-functionalized carbon surfaces. Overall, we a 5.2 ± 2.5-fold increase in ATP current with an approximately 9-fold increase in amine functionality, as analyzed by X-ray Photoelectron Spectroscopy, on the carbon surface was observed after modification with EDC-EDA. This provides evidence that amine-rich surfaces improve interactions with ATP on the surface. This study provides a detailed analysis of ATP interaction at carbon surfaces and ultimately a method to improve direct and rapid neurological ATP detection in the future.

6.
Phytomedicine ; 87: 153575, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33984593

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with limited treatment options. Conventional antitumor therapy combined with traditional Chinese medicine (TCM) to limit tumor progression has gradually become the focus of complementary and alternative therapies for HCC treatment. The Fuzheng Jiedu Xiaoji formulation (FZJDXJ) alleviates the clinical symptoms of patients and inhibits tumor progression, but its curative effect still requires extensive clinical research and mechanistic analysis. PURPOSE: To explore the effectiveness of FZJDXJ in HCC patients and investigate its biological function and mechanism underlying anticancer therapy. METHODS: This randomized controlled clinical trial enrolled 291 HCC patients receiving transcatheter arterial chemoembolization (TACE) therapy; patients received either FZJDXJ combined with standard treatment, or standard treatment alone, for 48 weeks. Statistical analyses were performed according to survival time at the end of the trial. The main constituents of the FZJDXJ extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. The antitumor effects of FZJDXJ and its specific biological mechanism of action were studied. RESULTS: After 48 weeks of treatment, one-year overall survival (OS) and progression-free survival (PFS) were significantly different between the two groups. Co-administration of FZJDXJ and TACE prolonged the OS of HCC patients, especially in BCLC A or B stage. FZJDXJ and TACE treatment effectively extended the PFS of patients, especially in the BCLC B stage. HPLC-MS/MS identified 1619 active constituents of FZJDXJ, including formononetin, chlorogenic acid (CGA), caffeic acid, luteolin, gallic acid, diosgenin, ergosterol endoperoxide, and lupeol, which may function through the AKT/CyclinD1/p21/p27 pathways. Through molecular docking, CGA and gallic acid could effectively combine with Thr308, an important phosphorylation site of AKT1. FZJDXJ inhibited tumor growth in nude mice. In vitro, FZJDXJ-mediated serum inhibited the proliferation, migration, and invasion of liver cancer cells, and promoted cell apoptosis. CONCLUSION: Clinically, FZJDXJ combined with TACE therapy significantly prolonged OS and PFS and reduced the mortality rate of HCC patients. Mechanistically, FZJDXJ effectively inhibited the proliferation and migration of liver cancer cells through the modulation of the AKT/CyclinD1/p21/p27 pathways, and may be a promising TCM drug for anti-HCC therapy.

7.
Sci Rep ; 11(1): 10640, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34017049

RESUMO

Methyl orange (MO) is a common anionic azo dye that is harmful to the environment and biology, so it must be treated innocuously before it can be discharged. Adsorption is an effective method to remove anionic dyes. Nanotube mineral is a natural one-dimensional adsorption material, and its unique morphology and structure endow it with good adsorption capacity. Although there are many related studies, there is a lack of in-depth discussions on the influence of nanotube's composition and structure on the adsorption of dyes and other pollutants. In this paper, two kinds of natural one-dimensional silicate minerals [halloysite nanotubes (HNTs) and chrysotile nanotubes (ChNTs)] with similar morphology but slightly different compositions and crystal structures were used as adsorbents, and MO solution was used as simulate pollutants. It is the first time to discuss in depth the influence of the composition and structure of nanotube minerals on their charge properties and the adsorption performance of methyl orange dyes. It is found that HNTs and ChNTs have different adsorption capacity due to the difference of electronegativity between Al3+ and Mg2+ in the crystal, so they possess negative and positive charges respectively in near-neutral solution, which leads to the adsorption capacity of MO by ChNTs with positive charges which is greater than that of HNTs.

8.
Luminescence ; 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34032371

RESUMO

It is meaningful and promising to develop a practical sensor toward melamine in dairy products with high sensitivity and selectivity. However, complicated composition and environment in milk necessitate stable luminophore as sensor with excellent photophysical properties. Herein, ultrathin graphitic carbon nitride nanosheet (CNNS) is prepared via successive thermal polymerization and acid exfoliation. The photophysical property of CNNS states its strong ultraviolet absorption and intense blue-light emission. Noteworthily, the CNNS could act as a chemo-sensor to detect trace melamine in dairy products. The high stability, eminent sensitivity, powerful selectivity and competitiveness substantiates that this CNNS luminophore is a promising sensor for melamine in dairy products, being of potentially practical value on monitoring milk quality.

9.
Methods Mol Biol ; 2285: 297-317, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33928561

RESUMO

The dynamic regulation of protein function by altered protein expression and post-translational modifications (PTMs) is essential for T cell function, but it has remained difficult to systemically quantify such events. Mass spectrometry (MS)-based proteomics has become a mainstream tool for comprehensive profiling of proteome and PTMs, especially with the development of multiplexed isobaric labeling methods, such as tandem mass tag (TMT), coupled with high-resolution two-dimensional liquid chromatography and tandem mass spectrometry (LC/LC-MS/MS). Here, we introduce a deep proteomics profiling protocol with an optimized 11-plex TMT-LC/LC-MS/MS platform to quantitate whole proteome, phosphoproteome, acetylome, and methylome in activated T cells. The major steps include preparation of activated T cells, protein extraction and digestion, TMT labeling, basic pH reverse phase LC, modified peptide enrichment, acidic pH reverse phase LC-MS/MS, and computational data processing. Approximately 10,000 proteins, 30,000 phosphosites, 2,000 lysine acetylated sites, and 1,000 lysine methylated sites can be identified and quantified from 1 mg of proteins per sample. Quality control steps are implemented in this protocol, and future development, such as nanoscale 16-plex TMT analysis, is discussed. This multiplexed and robust method provides a powerful tool for dissecting proteomic and PTM signatures in T cells at the systems level, and it is equally suitable for other biological samples, including effector T cell subsets.

10.
Adv Ther ; 38(5): 2472-2490, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33822328

RESUMO

INTRODUCTION: Cabozantinib and ramucirumab are approved for the treatment of adults with hepatocellular carcinoma (HCC) following prior sorafenib treatment; ramucirumab is restricted to use in patients with serum alpha-fetoprotein (AFP) ≥ 400 ng/mL. This matching-adjusted indirect comparison evaluated the efficacy and safety of both drugs after sorafenib in patients with HCC and AFP ≥ 400 ng/mL. METHODS: Individual patient data (IPD) from the CELESTIAL trial (cabozantinib) and population-level data from the REACH-2 trial (ramucirumab) were used. To align with REACH-2, the CELESTIAL population was limited to patients who received first-line sorafenib only and had baseline serum AFP ≥ 400 ng/mL. The IPD from CELESTIAL were weighted to balance the distribution of 11 effect-modifying baseline characteristics with those of REACH-2. Overall survival (OS; primary endpoint) and progression-free survival (PFS) were compared for the CELESTIAL (matching-adjusted) and REACH-2 populations using weighted Kaplan-Meier (KM) curves and parametric (OS, Weibull; PFS, log-logistic) modeling. Rates of treatment-related adverse events (TRAEs) and TRAE-related discontinuations were also compared. RESULTS: After matching and weighting, baseline characteristics were balanced between populations (REACH-2, N = 292; CELESTIAL, effective sample size = 105). Weighted KM estimates for OS (median [95% CI]) were not significantly different between cabozantinib and ramucirumab (10.6 [9.5-17.3] months versus 8.7 [7.3-10.8] months; p = 0.104), but PFS was significantly longer for cabozantinib than for ramucirumab (5.5 [4.6-7.4] months versus 2.8 [2.7-4.1] months; p = 0.016). Parametric modeling results were consistent with the weighted KM analysis. Rates of some grade 3 or 4 TRAEs were lower with ramucirumab than with cabozantinib; however, TRAE-related discontinuation rates were similar (p = 0.271). CONCLUSION: In this MAIC, cabozantinib significantly prolonged median PFS compared with ramucirumab after prior sorafenib treatment in patients with HCC and AFP ≥ 400 ng/mL; rates of some grade 3 or 4 TRAEs were lower with ramucirumab than cabozantinib but related discontinuation rates were not significantly different between treatments. TRIAL REGISTRATION: Clinical trials.gov identifiers: CELESTIAL trial (NCT01908426) and REACH-2 trial (NCT02435433). These slides can be retrieved under Electronic Supplementary Material.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Anilidas , Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Piridinas , Sorafenibe , alfa-Fetoproteínas
11.
Front Immunol ; 12: 647618, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796113

RESUMO

Objective: To evaluate the potential of serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (sGFAP) as disease biomarkers in neuromyelitis optica spectrum disorder (NMOSD) with aquaporin-4 antibody (AQP4-ab) or myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD). Methods: Patients with AQP4-ab-positive NMOSD (n = 51), MOGAD (n = 42), and relapsing-remitting multiple sclerosis (RRMS) (n = 31 for sNfL and n = 22 for sGFAP testing), as well as healthy controls (HCs) (n = 28), were enrolled prospectively. We assessed sNfL and sGFAP levels using ultrasensitive single-molecule array assays. Correlations of sNfL and sGFAP levels with clinical parameters were further examined in AQP4-ab-positive NMOSD and MOGAD patients. Results: sNfL levels were significantly higher in patients with AQP4-ab-positive NMOSD (median 17.6 pg/mL), MOGAD (27.2 pg/mL), and RRMS (24.5 pg/mL) than in HCs (7.4 pg/mL, all p < 0.001). sGFAP levels were remarkably increased in patients with AQP4-ab-positive NMOSD (274.1 pg/mL) and MOGAD (136.7 pg/mL) than in HCs (61.4 pg/mL, both p < 0.001). Besides, sGFAP levels were also significantly higher in patients with AQP4-ab-positive NMOSD compared to those in RRMS patients (66.5 pg/mL, p < 0.001). The sGFAP/sNfL ratio exhibited good discrimination among the three disease groups. sNfL levels increased during relapse in patients with MOGAD (p = 0.049) and RRMS (p < 0.001), while sGFAP levels increased during relapse in all three of the disease groups (all p < 0.05). Both sNfL and sGFAP concentrations correlated positively with Expanded Disability Status Scale scores in AQP4-ab-positive NMOSD (ß = 1.88, p = 0.018 and ß = 2.04, p = 0.032) and MOGAD patients (ß = 1.98, p = 0.013 and ß = 1.52, p = 0.008). Conclusion: sNfL and sGFAP levels are associated with disease severity in AQP4-ab-positive NMOSD and MOGAD patients, and the sGFAP/sNfL ratio may reflect distinct disease pathogenesis.

12.
Sci Rep ; 11(1): 6281, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737695

RESUMO

Pathological changes after third-generation drug-eluting stent implantation remain unclear. We compared the tissue responses of coronary arteries after the implantation of third-generation abluminal biodegradable-polymer everolimus-eluting stent (3rd EES) and second-generation durable-polymer EES (2nd EES) using autopsy specimens and an atherosclerotic porcine model. We compared the histology of stented coronary arteries obtained by autopsy performed 1-10 months after 3rd EES (n (number of cases) = 4, stent-implanted period of 3-7 months) and 2nd EES (n (number of cases) = 9, stent-implanted period of 1-10 months) implantations. The ratio of covered stent struts was higher with 3rd EESs than with 2nd EESs (3rd; 0.824 ± 0.032 vs. 2nd; 0.736 ± 0.022, p = 0.035). Low-density lipoprotein receptor knockout minipigs were stented with 3rd or 2nd EES in the coronary arteries and the stented regions were investigated. The fibrin deposition around the 2nd EES was more prominent. Additionally, higher density of smooth muscle cells was confirmed after the 3rd EES implantation. Pathological examination after the 3rd EES demonstrated a combination of less fibrin deposition and more rapid acquisition of well-developed neointima as compared to the 2nd EES at autopsy and the atherosclerotic porcine model.

13.
J Magn Reson Imaging ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33694250

RESUMO

BACKGROUND: Differential diagnosis of primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) is useful to guide treatment strategies. PURPOSE: To investigate the use of a convolutional neural network (CNN) model for differentiation of PCNSL and GBM without tumor delineation. STUDY TYPE: Retrospective. POPULATION: A total of 289 patients with PCNSL (136) or GBM (153) were included, the average age of the cohort was 54 years, and there were 173 men and 116 women. FIELD STRENGTH/SEQUENCE: 3.0 T Axial contrast-enhanced T1 -weighted spin-echo inversion recovery sequence (CE-T1 WI), T2 -weighted fluid-attenuation inversion recovery sequence (FLAIR), and diffusion weighted imaging (DWI, b = 0 second/mm2 , 1000 seconds/mm2 ). ASSESSMENT: A single-parametric CNN model was built using CE-T1 WI, FLAIR, and the apparent diffusion coefficient (ADC) map derived from DWI, respectively. A decision-level fusion based multi-parametric CNN model (DF-CNN) was built by combining the predictions of single-parametric CNN models through logistic regression. An image-level fusion based multi-parametric CNN model (IF-CNN) was built using the integrated multi-parametric MR images. The radiomics models were developed. The diagnoses by three radiologists with 6 years (junior radiologist Y.Y.), 11 years (intermediate-level radiologist Y.T.), and 21 years (senior radiologist Y.L.) of experience were obtained. STATISTICAL ANALYSIS: The 5-fold cross validation was used for model evaluation. The Pearson's chi-squared test was used to compare the accuracies. U-test and Fisher's exact test were used to compare clinical characteristics. RESULTS: The CE-T1 WI, FLAIR, and ADC based single-parametric CNN model had accuracy of 0.884, 0.782, and 0.700, respectively. The DF-CNN model had an accuracy of 0.899 which was higher than the IF-CNN model (0.830, P = 0.021), but had no significant difference in accuracy compared to the radiomics model (0.865, P = 0.255), and the senior radiologist (0.906, P = 0.886). DATA CONCLUSION: A CNN model can differentiate PCNSL from GBM without tumor delineation, and comparable to the radiomics models and radiologists. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

14.
J Neurol Neurosurg Psychiatry ; 92(7): 709-716, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33687975

RESUMO

BACKGROUND: Brain structural alterations and their clinical significance of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) have not been determined. METHODS: We recruited 35 MOGAD, 38 aquaporin 4 antibody positive neuromyelitis optica spectrum diseases (AQP4+ NMOSD), 37 multiple sclerosis (MS) and 60 healthy controls (HC) who underwent multimodal brain MRI from two centres. Brain lesions, volumes of the whole brain parenchyma, cortical and subcortical grey matter (GM), brainstem, cerebellum and cerebral white matter (WM) and diffusion measures (fractional anisotropy, FA and mean diffusivity, MD) were compared among the groups. Associations between the MRI measurements and the clinical variables were assessed by partial correlations. Logistic regression was performed to differentiate MOGAD from AQP4+ NMOSD and MS. RESULTS: In MOGAD, 19 (54%) patients had lesions on MRI, with cortical/juxtacortical (68%) as the most common location. MOGAD and MS showed lower cortical and subcortical GM volumes than HC, while AQP4+ NMOSD only demonstrated a decreased cortical GM volume. MS demonstrated a lower cerebellar volume, a lower FA and an increased MD than MOGAD and HC. The subcortical GM volume was negatively correlated with Expanded Disability Status Scale in MOGAD (R=-0.51; p=0.004). A combination of MRI and clinical measures could achieve an accuracy of 85% and 93% for the classification of MOGAD versus AQP4+ NMOSD and MOGAD versus MS, respectively. CONCLUSION: MOGAD demonstrated cortical and subcortical atrophy without severe WM rarefaction. The subcortical GM volume correlated with clinical disability and a combination of MRI and clinical measures could separate MOGAD from AQP4+ NMOSD and MS.

15.
J Am Soc Mass Spectrom ; 32(4): 936-945, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33683887

RESUMO

The linear sequence of amino acids in a protein folds into a 3D structure to execute protein activity and function, but it is still challenging to profile the 3D structure at the proteome scale. Here, we present a method of native protein tandem mass tag (TMT) profiling of Lys accessibility and its application to investigate structural alterations in human brain specimens of Alzheimer's disease (AD). In this method, proteins are extracted under a native condition, labeled by TMT reagents, followed by trypsin digestion and peptide analysis using two-dimensional liquid chromatography and tandem mass spectrometry (LC/LC-MS/MS). The method quantifies Lys labeling efficiency to evaluate its accessibility on the protein surface, which may be affected by protein conformations, protein modifications, and/or other molecular interactions. We systematically optimized the amount of TMT reagents, reaction time, and temperature and then analyzed protein samples under multiple conditions, including different labeling time (5 and 30 min), heat treatment, AD and normal human cases. The experiment profiled 15370 TMT-labeled peptides in 4475 proteins. As expected, the heat treatment led to extensive changes in protein conformations, with 17% of the detected proteome displaying differential labeling. Compared to the normal controls, AD brain showed different Lys accessibility of tau and RNA splicing complexes, which are the hallmarks of AD pathology, as well as proteins involved in transcription, mitochondrial, and synaptic functions. To eliminate the possibility that the observed differential Lys labeling was caused by protein level change, the whole proteome was quantified with standard TMT-LC/LC-MS/MS for normalization. Thus, this native protein TMT method enables the proteome-wide measurement of Lys accessibility, representing a straightforward strategy to explore protein structure in any biological system.

16.
Semin Ophthalmol ; : 1-8, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33734947

RESUMO

Purpose: To explore the feasibility of corneal morphological and biomechanical parameters for keratoconus and forme fruste keratoconus diagnosis.Methods: This case-control study included a total of 517 eyes from 408 keratoconus patients (KC group), 83 eyes from 83 forme fruste keratoconus patients (FFKC group), and 158 eyes from 158 patients with normal corneas (NL group). All subjects underwent routine ophthalmologic examinations. Pentacam and Corneal Visualization Scheimpflug Technology (Corvis ST) were used to obtain corneal morphological and biomechanical parameters. Differences between groups were compared using receiver operating characteristic (ROC) curve analysis.Results: ROC analysis showed that all corneal morphological parameters and most biomechanical parameters distinguished KC from NL, with an area under the curve (AUC) greater than 0.80, of which Belin-Ambrósio enhanced ectasia total deviation index (BAD-D) and tomographic and biomechanical index (TBI) were most efficient. The AUC for distinguishing KC from NL of the BAD-D was 0.989 and the TBI was 0.993, which were not statistically significant (DeLong et al., P= .232). The BAD-D cut-off point of 1.595 provided 95.9% sensitivity for distinguishing KC from NL with 100% specificity. The TBI cut-off point of 0.515 provided 96.7% sensitivity for distinguishing KC from NL with 100% specificity. The ability of other parameters to distinguish KC from NL was lower than that of BAD and TBI. Except for central astigmatism from the anterior corneal surface (AstigF), the AUC that distinguished FFKC from NL was 0.862. The AstigF cut-off point of 4.65 provided 73.5% sensitivity for distinguishing FFKC from NL with 99.3% specificity. Other parameters distinguished FFKC from NL with low efficiency. Among them, the AUC for distinguishing FFKC from NL of the TBI was 0.722, whose cut-off point of 0.273 provided 55.4% sensitivity for distinguishing KC from NL with 79.7% specificity.Conclusion: BAD-D and TBI have the highest efficiency, sensitivity, and specificity for distinguishing KC from NL. Except for AstigF, other corneal morphological and biomechanical parameters have a relatively low ability to distinguish FFKC from NL.

17.
Oncol Rep ; 45(3): 1306-1314, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33650669

RESUMO

Non­small cell lung cancer (NSCLC) remains an intractable disease, which is primarily due to tumor metastasis and the acquisition of resistance to chemotherapy. Therefore, there is an urgent need for novel therapeutics to overcome these obstacles. It was recently demonstrated that upregulated expression of monoamine oxidase A (MAOA) contributes to the progression of NSCLC. G10, a tumor­targeting representative conjugate of heptamethine carbocyanine dye and an inhibitor of MAOA, was shown to exert potent cytotoxic effects, comparable to those of doxorubicin, against prostate cancer cell lines, as well as moderate MAOA inhibitory activity. The research described herein aimed to extend our previous study on the antitumor function of G10 in NSCLC in vitro and in vivo, and to elucidate the mechanisms through which G10 exerts its antineoplastic effects. G10 markedly inhibited the proliferation of paclitaxel­resistant NSCLC cells (H460/PTX) and reduced tumor cell migration and invasion. Gene expression profiling of paclitaxel­resistant NSCLC cells following treatment with G10 demonstrated that the expression of genes associated with the extracellular matrix was significantly affected, particularly the metastasis­related genes matrix metallopeptidase (MMP)2, MMP14 and COL6A, which exhibited notably reduced expression. Additionally, the results also demonstrated that MAOA­related pathways, including AKT and hypoxia­inducible factor­1α, were also inhibited by G10 treatment and, subsequently, the downstream molecules of these pathways, such as p21, MMP2 and vascular endothelial growth factor, were also downregulated, highlighting a possible mechanism through which G10 suppresses tumor cell migration, invasion and proliferation. Importantly, in mouse NSCLC xenografts, combined treatment with G10 and paclitaxel resulted in pronounced inhibition of tumor growth. Taken together, the results of the present study highlight the potential of G10 as a novel therapeutic targeting MAOA in paclitaxel­resistant NSCLC.

18.
ACS Appl Mater Interfaces ; 13(7): 8736-8744, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33565848

RESUMO

Integrating nanostructured active materials, antimicrobial components, and rational porous structures is one of the promising approaches for simultaneously boosting removal efficiency, antimicrobial capacity, mechanical property, hydrophobic performance, and air permeability of air filters. However, realizing these performances of an air filter still remains a big challenge. Herein, a multifunctional air filter zNFs-Ag@PT, which is composed of a unique substrate prepared from Ag nanoparticles (AgNPs)-paper towel (PT) microfibers and an upper layer formed from aligned zein nanofibers (zNFs) inspired by a "tug-of-war" repulsion force, is reported. The Ag@PT substrate is fabricated via in situ reduction; and zNFs are prepared by electrospinning a well-prepared zein Pickering emulsion onto a specially designed collector. The innovative collector is a partially conductive design composed of an insulative middle section and two conductive ends. It is demonstrated that the introduction of AgNPs not only endows the zNFs-Ag@PT filter with an effective antimicrobial activity but also provides the substrate with an anisotropic electric field to achieve stretched and aligned zein fibers forming thinner nanofibers than that without AgNPs. As a result, the filtration performances of a zNFs-Ag@PT filter are enhanced. This study initiates an effective way to fabricate bio-based multifunctional air filters with antimicrobial and filtration performances via combining nano- and biotechnology.

20.
Bioorg Med Chem Lett ; 35: 127775, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33412152

RESUMO

Seventeen flavonoids (1-17) were isolated from Sophora alopecuroides L.. Compounds 1 and 2 were new compounds, and compounds 5, 8, 11, 12, and 17 were isolated from S. alopecuroides for the first time. The sources of compounds 1 and 2 were determined from the seeds of S. alopecuroides by UPLC-QE-Orbitrap-MS, and compounds 1, 2, 7, 13, 14, 15, 16, and 17 were proven to improve the insulin resistance of C2C12 myotubes and significantly increase glucose consumption levels. Among them, compounds 1, 2, 13, 14, 16, and 17 could bind to protein tyrosine phosphatase 1B (PTP1B), thereby significantly inhibiting the enzyme activity of PTP1B. Compound 2 had the strongest inhibitory effect, with an inhibition rate of 95.22% at 0.1 µg mL-1.

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