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1.
J Gene Med ; 23(3): e3319, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33527480

RESUMO

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Genetic factors play important roles in PD risk. rs653765 and rs514049 of ADAM10 were reported to be associated with Alzheimer's disease (AD) in Caucasian population; however, the association of the two variants with PD in Chinese Han population remains unknown. The present investigation aimed to explore the possible association of ADAM10 variants with PD in Chinese Han population. METHODS: We enrolled 565 PD patients and 518 healthy controls to conduct a case-control study. DNA samples were extracted from peripheral blood leukocytes, and the genotypes were determined by utilization of MassARRAY platform. Plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: We found CC genotype of rs514049 was associated with an increased risk of PD (OR (95% CI) = 3.776 (1.127-11.217), p = 0.018). The C allele frequency of rs514049 was significantly higher in PD group (OR (95% CI) = 1.328 (1.031-1.709), p = 0.028), especially in male subgroup (OR (95% CI) = 1.484 (1.053-2.092), p = 0.024). However, there was no significant difference in the genotype or allele frequencies for rs653765 within the groups. Plasma levels were significantly decreased in PD patients compared with controls (p < 0.001). CONCLUSIONS: Our data suggested that C allele of rs514049 in ADAM10 may increase the risk of PD in Chinese Han population, especially in males. The decreased plasma levels are probably involved in PD development.

2.
Anal Chim Acta ; 1146: 33-40, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33461717

RESUMO

Fluorescence quenching of carbon nanodots by metal ions has been extensively applied for the determination of oligonucleotides, proteins, small molecules and metal ions. However, the problem of poor selectivity originating from the coordination of surface oxygen-containing groups to many kinds of metal ions has limited the prosperity of carbon nanodots in detection field. Herein, the specific recognition of carbon nanodots to Hg2+ is controlled by rational regulation of the surface structure of carbon nanodots. Passivation of the surface carboxyl and hydroxyl groups plays a decisive role in inhibiting the binding of metal ions with carbon nanodots. Upon the attachment of Hg2+ specific recognition unit, carbon nanodots exhibited a high selectivity to Hg2+. This work facilitates to rationally design the surface structure of carbon nanodots to obtain the desirable selective recognition ability.

3.
Cancer Sci ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33440047

RESUMO

Clinically, patients with urothelial carcinoma of the bladder (UCB) with tumor metastasis are incurable. To find new therapeutic strategies, the mechanisms underlying UCB invasion and metastasis should be further investigated. In this study, zinc finger and homeobox 3 (ZHX3) was first screened as a critical oncogenic factor associated with poor prognosis in a UCB dataset from The Cancer Genome Atlas (TCGA). These results were also confirmed in a large cohort of clinical UCB clinical samples. Next, we found that ZHX3 could promote the migration and invasion capacities of UCB cells both in vitro and in vivo. Mechanistically, coimmunoprecipitation (coIP) and mass spectrometry (MS) analysis indicated that ZHX3 was a target of tripartite motif 21 (TRIM21), which mediates its ubiquitination and subsequent degradation. Notably, RNA-seq analysis showed that ZHX3 repressed the expression of regulator of G protein signaling 2 (RGS2). Generally, our results suggest that ZHX3 plays an oncogenic role in UCB pathogenesis and might serve as a novel therapeutic target for UCB.

4.
Talanta ; 223(Pt 1): 121721, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33303167

RESUMO

Fluorescence anisotropy (FA) has been widely applied for detecting and monitoring special targets in life sciences. However, matrix autofluorescence restricted its further application in complex biological samples. Herein, we report a near-infrared-II (NIR-II) FA strategy for detecting adenosine triphosphate (ATP) in human serum samples and breast cancer cell lysate, which employed NIR-II fluorescent Ag2Se quantum dots (QDs) as tags to reduce matrix autofluorescence effect and applied graphene oxide (GO) to enhance fluorescence anisotropy signals. In the presence of ATP, the recognition between NIR-II Ag2Se QDs labeled aptamer (QD-pDNA) and ATP led to the release of QD-pDNA from GO, resulting in the obvious decrease of FA values. ATP could be quantitatively detected in concentrations ranged from 3 nM to 2500 nM, with a detection limit down to 1.01 nM. This study showed that the developed NIR-II FA strategy could be applied for detecting targets in complex biological samples and had great potential for monitoring interactions between biomolecules in biomedical research.

5.
Anal Chem ; 93(3): 1757-1763, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33373183

RESUMO

An ultrasensitive electrochemiluminescence (ECL) biosensor was proposed based on a closed bipolar electrode (BPE) for the detection of alkaline phosphatase (ALP). For most of the BPE-ECL biosensors, an effective signal amplification strategy was the key to enhance the sensitivity of the system. Herein, the signal amplification strategy of the enzyme catalysis was utilized in the BPE-ECL system. Au nanoparticles (NPs) were electrodeposited on the cathode surface of the ITO electrode to improve the stability and sensitivity of the signal. Compared with the previous BPE-ECL biosensors, the sensitivity was increased by at least 3 orders of magnitude. The biosensor showed high sensitivity and specificity of ALP detection with a detection limit of as low as 3.7 aM. Besides, it was further applied to the detection of ALP in different types of cells and successfully realized ALP detection in single Hep G2 cell, which had a huge application prospect in single biomolecule detection or single cell analysis.


Assuntos
Fosfatase Alcalina/análise , Técnicas Biossensoriais , Técnicas Eletroquímicas , Medições Luminescentes , Análise de Célula Única , Fosfatase Alcalina/metabolismo , Eletrodos , Ouro/química , Células Hep G2 , Humanos , Nanopartículas Metálicas/química
6.
Microb Cell Fact ; 19(1): 223, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287813

RESUMO

BACKGROUND: Genome reduction and metabolic engineering have emerged as intensive research hotspots for constructing the promising functional chassis and various microbial cell factories. Surfactin, a lipopeptide-type biosurfactant with broad spectrum antibiotic activity, has wide application prospects in anticancer therapy, biocontrol and bioremediation. Bacillus amyloliquefaciens LL3, previously isolated by our lab, contains an intact srfA operon in the genome for surfactin biosynthesis. RESULTS: In this study, a genome-reduced strain GR167 lacking ~ 4.18% of the B. amyloliquefaciens LL3 genome was constructed by deleting some unnecessary genomic regions. Compared with the strain NK-1 (LL3 derivative, ΔuppΔpMC1), GR167 exhibited faster growth rate, higher transformation efficiency, increased intracellular reducing power level and higher heterologous protein expression capacity. Furthermore, the chassis strain GR167 was engineered for enhanced surfactin production. Firstly, the iturin and fengycin biosynthetic gene clusters were deleted from GR167 to generate GR167ID. Subsequently, two promoters PRsuc and PRtpxi from LL3 were obtained by RNA-seq and promoter strength characterization, and then they were individually substituted for the native srfA promoter in GR167ID to generate GR167IDS and GR167IDT. The best mutant GR167IDS showed a 678-fold improvement in the transcriptional level of the srfA operon relative to GR167ID, and it produced 311.35 mg/L surfactin, with a 10.4-fold increase relative to GR167. CONCLUSIONS: The genome-reduced strain GR167 was advantageous over the parental strain in several industrially relevant physiological traits assessed and it was highlighted as a chassis strain for further genetic modification. In future studies, further reduction of the LL3 genome can be expected to create high-performance chassis for synthetic biology applications.

7.
J Gene Med ; : e3302, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33295114

RESUMO

BACKGROUND: Clusterin (CLU) plays important role in the pathology of neurodegenerative disorders. Recently, genetic variant of CLU rs9331896 has been reported as a risk estimate for Alzheimer disease (AD). However, the association between this variant and risk of Parkinson's disease (PD) in Chinese Han population remains elusive. METHODS: We sequenced CLU rs9331896 in 353 PD patients and 326 healthy-matched individuals of Chinese Han population. The genotypes of rs9331896 were analyzed by Agena MassArray in accordance with the platform directions. The distribution of genotypes and allelic frequencies was analyzed by Chi-square test. Additionally, the expression of CLU protein in plasma was evaluated by enzyme-linked immunosorbent Assay (ELISA) and analysed with T test. RESULTS: TT genotype in rs9331896 in a recessive model was found to be associated with the increased risk of PD (OR=1.408, 95%CI = (1.034, 1.916), p=0.029). Subgroup analysis indicated that TT genotype carriers showed a significantly higher risk in male PD patients when compared to male healthy controls (OR=1.611, 95%CI = (1.046, 2.483), p =0.030). Besides, CLU levels in plasma of PD patients were significantly higher than controls (p =0.024). CONCLUSIONS: CLU-rs9331896-TT genotype was a risk factor for PD, particularly in males. PD patients also expressed a high level of CLU in plasma.

8.
Nanomedicine ; : 102340, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33227540

RESUMO

Copper(II) diethyldithiocarbamate complex (CuET), the metabolite of disulfiram complexed with copper, is the component responsible for cancer treatment efficacy of disulfiram. But the hydrophobic property of CuET limits its use in vivo, and an appropriate drug delivery system needs to be developed. Ultrasmall melanin nanoparticle (M-Dot) with excellent biosafety and biocompatibility properties has been synthesized in our previous studies. Herein we prepared CuET loaded with M-Dots through hydrophobic interaction, which could enhance the water solubility significantly. After the administration of M-Dots-CuET in mice tumor models, the nanoparticles showed good tumor accumulation as evidenced by the enhanced photoacoustic signal in tumor regions. M-Dots-CuET also displayed excellent tumor inhibition capability, and the tumor growth inhibition value (TGI) was 45.1%. When combined with photothermal therapy, the TGI reached up to 78.6%. In summary, M-Dots-CuET provide a new potential strategy for cancer theranostics.

9.
Am J Transl Res ; 12(10): 6524-6536, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194049

RESUMO

BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a lethal disease with poor treatment response and a high death rate. Immune cells infiltrating the tumor tissues have been shown to play a vital role in tumorigenesis and tumor progression, but their prognostic significance in MIBC remains unclear. OBJECTIVES: To explore the landscape and prognostic significance of tumor-infiltrating immune cells (TIICs) in MIBC, and to develop a model to improve the prognostic predictions of MIBC. METHODS AND MATERIALS: The gene expression profile and clinical data of MIBC patients were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas portal. The fractions of 22 TIIC subtypes were calculated using the Cell Type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm. A TIICs-based model was constructed using least absolute shrinkage and selection operator (LASSO) Cox regression in a training cohort and validated in the validation cohort. RESULTS: Ten types of TIICs demonstrated different infiltration abundance between MIBC and normal tissue. We also found 11 types of TIICs that were significantly associated with overall survival (OS). A TIICs-based model was established, consisting of 15 types of immune cells, and an immunoscore was calculated. Significant differences in OS were found between the high and low immunoscore groups, in both training (n = 343) and validation (n = 146) cohorts. The model could identify patients who would have worse OS despite having similar clinical characteristics. Furthermore, multivariate analysis identified the immunoscore as an independent risk factor (hazard ratio, 3.23; 95% confidence interval; 2.22-4.70) for OS in MIBC patients. CONCLUSION: The landscape of immune infiltration is different between MIBC and normal tissue. The TIICs-based model could provide promising predictive value to complement the existing staging system for predicting the OS of MIBC patients.

10.
Exp Cell Res ; : 112389, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33221316

RESUMO

Ischemia-reperfusion (I/R) injury is a multifactorial process triggered when an organ is subjected to transiently reduced blood supply. The result is a cascade of pathological complications and organ damage due to the production of reactive oxygen species following reperfusion. The present study aims to evaluate the role of activated calcium-sensing receptor (CaR)-cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway in I/R injury. Firstly, an I/R rat model with CSE knockout was constructed. Transthoracic echocardiography, TTC and HE staining were performed to determine the cardiac function of rats following I/R Injury, followed by TUNEL staining observation on apoptosis. Besides, with the attempt to better elucidate how CaR-CSE/H2S affects I/R, in-vitro culture of human coronary artery endothelial cells (HCAECs) was conducted with gadolinium chloride (GdCl3, a CaR agonist), H2O2, siRNA against CSE (siCSE), or W7 (a CaM inhibitor). The interaction between CSE and CaM was subsequently detected. Plasma oxidative stress indexes, H2S and CSE, and apoptosis-related proteins were all analyzed following cell apoptosis. We found that H2S elevation led to the improvement whereas CSE knockdown decreased cardiac function in rats with I/R injury. Moreover, oxidative stress injury in I/R rats with CSE knockout was aggravated, while the increased expression of H2S and CSE in the aortic tissues resulted in alleviated the oxidative stress injury. Moreover, increased H2S and CSE levels were found to inhibit cell apoptotic ability in the aortic tissues after I/R injury, thus attenuating oxidative stress injury, accompanied by inhibited expression of apoptosis-related proteins. In HCAECs following oxidative stress treatment, siCSE and CaM inhibitor were observed to reverse the protection of CaR agonist. Coimmunoprecipitation assay revealed the interaction between CSE and CaM. Taken together, all above-mentioned data provides evidence that activation of the CaR-CSE/H2S pathway may confer a potent protective effect in cardiac I/R injury.

11.
Postgrad Med ; : 1-7, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33131368

RESUMO

Objective: The current study was to evaluate the association of Lipoprotein (a) [Lp(a)] and in-hospital outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods: ACS patients undergoing PCI were retrospectively enrolled. Based on Lp(a) level, patients were divided into low (<30 mg/dL) and high (≥30 mg/dL) Lp(a) groups. Results: Compared to those with low Lp(a), patients with high Lp(a) had larger numbers of coronary arteries ≥70% stenosis and had longer coronary artery lesion (P < 0.05). After adjustment for covariates, high Lp(a) remained associated with higher odds of having coronary artery ≥70% stenosis, type C coronary lesion and pre-PCI TIMI flow grade 1/0. Patients with high Lp(a) had a higher unadjusted odds of acute stent thrombosis (odds ratio [OR] 1.10 and 95% confidence interval [CI] 1.01-2.27), congestive heart failure (OR 1.24 and 95% CI 1.15-2.38) and composite in-hospital outcomes (OR 1.28 and 95% CI 1.18-2.42). After adjustment for covariates, patients with high Lp(a) still had a higher odds of congestive heart failure (OR 1.08 and 95% CI 1.01-1.78) and composite in-hospital outcomes (OR 1.12 and 95% CI 1.04-1.81). Conclusion: In ACS patients undergoing PCI, compared to those with low Lp(a), patients with high Lp(a) had more severe coronary artery lesion, higher risk of congestive heart failure and composite in-hospital outcomes.

12.
Cell Death Dis ; 11(10): 897, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093440

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disease characterized by Lewy body formation and progressive dopaminergic neuron death in the substantia nigra (SN). Genetic susceptibility is a strong risk factor for PD. Previously, a rare gain-of-function variant of GLUD2 glutamate dehydrogenase (T1492G) was reported to be associated with early onset in male PD patients; however, the function and underlying mechanism of this variant remains elusive. In the present study, we generated adeno-associated virus expressing GLUD2 and its mutant under the control of the glial fibrillary acidic protein promotor and injected the virus into the SN pars compacta of either untreated mice or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. Our results demonstrate that GLUD2 mutation in MPTP-induced PD mice exacerbates movement deficits and nigral dopaminergic neuron death and reduces glutamate transporters expression and function. Using GC-Q-TOF/MS-based metabolomics, we determined that GLUD2 mutation damages mitochondrial function by decreasing succinate dehydrogenase activity to impede the tricarboxylic acid cycle in the SN of MPTP-induced PD mice. Accordingly, GLUD2 mutant mice had reduced energy metabolism and increased apoptosis, possibly due to downregulation of brain-derived neurotrophic factor/nuclear factor E2-related factor 2 signaling in in vitro and in vivo PD models. Collectively, our findings verify the function of GLUD2 in PD and unravel a mechanism by which a genetic variant in human GLUD2 may contribute to disease onset.

13.
Medicine (Baltimore) ; 99(27): e20794, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629663

RESUMO

BACKGROUND: Recently, trimethylamine N-oxide (TMAO) unexplained gut microbe has been proposed as a promising risk factor for atherosclerotic cardiovascular disease (CVD) pathogenesis and adverse events. The relationship of TMAO with coronary atherosclerotic burden has been evaluated in patients with stable coronary artery disease and ST-segment elevation myocardial infarction, but still needs to be explored in newly diagnosed non-ST-segment elevation myocardial infarction (NSTEMI) patients. MATERIAL AND METHODS: A prospective, single-center, SZ-NSTEMI trial (ChiCTR1900022366) is underway to investigate the relationship of TMAO with the severity and prognosis of coronary atherosclerosis in newly diagnosed NSTEMI patients who will undergo coronary angiography with primary percutaneous coronary intervention (pPCI). The primary endpoint of the study will be assessed the association of TMAO with coronary atherosclerotic severity quantify by the number of diseased coronary arteries and SYNTAX score after the coronary angiography. The secondary endpoints will be identified the TMAO as a prognostic biomarker for the short (1 month) and long-term (12 months) major cardiovascular and cerebrovascular events (MACCEs) rate including myocardial infarction, target vessel revascularization, stroke, heart failure, all-cause rehospitalization, and all-cause mortality after the pPCI. The blood samples will be collected from each patient before the procedure to measure the TMAO by isotope dilution high-performance liquid chromatography. In conclusion, SZ-NSTEMI will be the first cohort that will be investigated the association of TMAO with the severity and prognosis of coronary atherosclerotic burden in NSTEMI patients, aiming to identify TMAO as a predictor and a prognostic biomarker.


Assuntos
Aterosclerose/patologia , Doença da Artéria Coronariana/patologia , Metilaminas/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/patologia , Adolescente , Adulto , Idoso , Biomarcadores , Doenças Cardiovasculares/patologia , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
14.
Minerva Med ; 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32512976

RESUMO

BACKGROUND: The purpose of this study was to explore the mechanism by which microRNA-196b exerts a tumor promotion effect on ovarian cancer (OCa). METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of microRNA-196b in 60 pairs of tumor samples and paracancerous ones collected from patients with ovarian cancer, meanwhile, microRNA-196b expression in human ovarian cancer cell lines and normal ovarian epithelial cell lines were also analyzed by qRT-PCR. Bioinformatics methods suggested that ZMYND11 was predicted the target gene of microRNA-196b and its binding relationship was verified by dual luciferase reporter gene experiment. Then cell counting kit (CCK-8) and 5-Ethynyl-2'- deoxyuridine (EdU) assay were performed to analyze the influence of microRNA-196b overexpression on OCa cell proliferation. RESULTS: QRT-PCR results showed that microRNA-196b level in OCa tissues was remarkably higher than that in normal ovarian tissues, which was closely relevant to the poor prognosis of tumors. The dual luciferase reporter gene experiments confirmed that microRNA-196b could directly bind to the 3'-UTR of ZMYND11. Overexpression of microRNA-196b remarkably enhanced the proliferation, invasiveness and migratory ability of OCa cells. Meanwhile, overexpression of microRNA-196b significantly decreased ZMYND11 mRNA and protein expression. In addition, ZMYND11 level was also significantly increased in ovarian cancer cells. Compared with the miRNA-NC group, microRNA-196b-mimics + ZMYND11-OE treatment reversed the effect of microRNA-196b-mimics on OCa cell functions. CONCLUSIONS: MicroRNA-196b was highly expressed in OCa tissues, which can promote the proliferation, invasiveness and migratory ability of OCa cells by targeting ZMYND11. In addition, the expression disorder of microRNA-196b was associated with the malignant development of OCa.

15.
ACS Omega ; 5(24): 14261-14266, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32596562

RESUMO

Near-infrared (NIR) fluorescence has attracted much attention in biomedical fields because it offers deep tissue penetration and high spatial resolution. Herein, a method is developed for the preparation of NIR fluorescent nanocomposites (NCs) by encapsulating natural chlorophyll (Chl) into the micelles of octylamine-modified poly(acrylic acid) (OPA). Both femtosecond transient absorption spectra and isothermal titration calorimetry thermogram reveal that the micelles of OPA provide a hydrophobic environment for the improved fluorescence efficiency. Hence the resulted Chl NCs possess unique properties such as ultrasmall size, outstanding photostability, good biocompatibility, and superbright NIR fluorescence emission. In vivo imaging of sentinel lymph node is achieved in nude mice, demonstrating the potential of Chl NCs in biomedical applications. This work provides a new strategy for the preparation of highly biocompatible NIR fluorescence labeling nanocomposites.

16.
J Bioenerg Biomembr ; 52(4): 257-268, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32472432

RESUMO

To investigate the effect of hydrogen-rich water on myocardial tissue metabolism in a myocardial ischemia-reperfusion injury (MIRI) rat model. Twelve rats were randomly divided into a hydrogen-rich water group and a control group of size 6 each. After the heart was removed, it was fixed in the Langendorff device, and the heart was perfused with 37 °C perfusion solution pre-balanced with oxygen. The control group was perfused with Kreb's-Ringers (K-R) solution, and the hydrogen-rich water group was perfused with K-R solution + hydrogen-rich water. Liquid Chromatograph Mass Spectrometer (LC-MS) analysis platform was used for metabolomics research. Principle component analysis (PCA), partial least squares discriminant analysis (PLS-DA), orthogonal partial least squares discriminant analysis (OPLS-DA), Variable importance in projection (VIP) value of OPLS-DA model (threshold value ≥1) were employed with independent sample T Test (p < 0.05) to find differentially expressed metabolites, and screen for differential metabolic pathways. VIP (OPLS-DA) analysis was performed with T test, and the metabolites of the control group and the hydrogen-rich water group were significantly different, and the glycerophospholipid metabolism was screened. Seven myocardial ischemia-reperfusion injury (MIRI)-related signaling pathways were identified, including glycerophospholipid metabolism, glycosylphosphatidylinositol (GPI) anchored biosynthesis, and purine metabolism, as well as 10 biomarkers such as phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine. Hydrogen-rich water regulates the metabolic imbalance that could change MIRI myocardial tissue metabolism, and alleviate ischemia-reperfusion injury in isolated hearts of rats through multiple signaling pathways.

17.
Angew Chem Int Ed Engl ; 59(28): 11240-11244, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32246736

RESUMO

Comprehensive phenotypic profiling of heterogeneous circulating tumor cells (CTCs) at single-cell resolution has great importance for cancer management. Herein, a novel spectrally combined encoding (SCE) strategy was proposed for multiplex biomarker profiling of single CTCs using a multifunctional nanosphere-mediated microfluidic platform. Different cellular biomarkers uniquely labeled by multifunctional nanosphere barcodes, possessing identical magnetic tags and distinct optical signatures, enabled isolation of heterogeneous CTCs with over 91.6 % efficiency and in situ SCE of phenotypes. By further trapping individual CTCs in ordered microstructures on chip, composite single-cell spectral signatures were conveniently and efficiently obtained, allowing reliable spectral-readout for multiplex biomarker profiling. This SCE strategy exhibited great potential in multiplex profiling of heterogeneous CTC phenotypes, offering new avenues for cancer study and precise medicine.

19.
Anal Chem ; 92(7): 5258-5266, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32156113

RESUMO

To enhance signal acquisition stability and diminish background interference for conventional flow bead-based fluorescence detection methods, we demonstrate here an exceptional microfluidic chip assisted platform by integrating near-infrared optical tweezers with upconversion luminescence encoding. For the former, a single 980 nm laser is employed to perform optical trapping and concurrently excite upconversion luminescence, avoiding the fluctuation of the signals and the complexity of the apparatus. By virtue of the favorable optical properties of upconversion nanoparticles (UCNPs), the latter is carried out by employing two-color UCNPs (Er-UCNPs and Tm-UCNPs) with negligible spectral overlaps. With the assistance of the double key techniques, we fabricated complex microbeads referred to a UCNPs-miRNAs-microbead sandwich construct by a one-step nucleic acid hybridization process and then obtained uniform terrace peaks for the automatic and simultaneous quantitative determination of miRNA-205 and miRNA-21 sequences with a detection limit of pM level on the basis of a special home-built flow bead platform. Furthermore, the technique was successfully applied for analyzing complex biological samples such as cell lysates and human tissue lysates, holding certain potential for disease diagnosis. In addition, it is expected that the flow platform can be utilized to investigate many other biomolecules of single cells and to allow analysis of particle heterogeneity in biological fluid by means of optical tweezers.

20.
World J Urol ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32215675

RESUMO

OBJECTIVE: To access the surgical and oncological outcomes of simultaneous thulium laser enucleation of bladder tumor (ThuLEBT) and thulium laser enucleation of prostate (ThuLEP) in patients with non-muscle invasive bladder tumor (NMIBC) and benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Between June 2009 and June 2017, 118 men with NMIBC who underwent simultaneous ThuLEBT and ThuLEP and fulfilled the inclusion criteria were matched with 118 patients who received ThuLEBT alone. Clinicopathological parameters, surgical outcome data and oncological outcomes were retrospectively analyzed and compared. RESULTS: The patients who underwent simultaneous ThuLEBT and ThuLEP experienced a longer length of operation time (70.4 vs. 25.5 min; p < 0.001), but there were no statistically significant differences in catheterization period, hospital stay and complication between the two groups. At a mean follow-up of 58.7 and 55.8 months in ThuLEBT/ThuLEP group and ThuLEBT group, no significant differences in overall recurrence rates, progression rates, recurrence in the bladder neck/prostatic fossa and mean elapsed time to recurrence were detected. The 5-year recurrence-free probability was 73.2% for ThuLEBT/ThuLEP and 69.2% for ThuLEBT (p = 0.361). CONCLUSIONS: Our results indicate that simultaneous ThuLEBT and ThuLEP can be safely performed without increasing the surgical risk and the risk of tumor recurrence and progression in patients with NMIBC and BPH, and it may be preferred alternative for select patients.

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