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1.
Biosens Bioelectron ; 258: 116354, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38723331

ABSTRACT

Real-time monitoring of biological markers in sweat is a valuable tool for health assessment. In this study, we have developed an innovative wearable biosensor for precise analysis of glucose in sweat during physical activities. The sensor is based on a single-atom catalyst of platinum (Pt) uniformly dispersed on tricobalt tetroxide (Co3O4) nanorods and reduced graphene oxide (rGO), featuring a unique three-dimensional nanostructure and excellent glucose electrocatalytic performance with a wide detection range of 1-800 µM. Additionally, density functional theory calculations have revealed the synergetic role of Pt active sites in the Pt single-atom catalyst (Co3O4/rGO/Pt) in glucose adsorption and electron transfer, thereby enhancing sensor performance. To enable application in wearable devices, we designed an S-shaped microfluidic chip and a point-of-care testing (POCT) device, both of which were validated for effectiveness through actual use by volunteers. This research provides valuable insights and innovative approaches for analyzing sweat glucose using wearable devices, contributing to the advancement of personalized healthcare.


Subject(s)
Biosensing Techniques , Glucose , Graphite , Platinum , Sweat , Wearable Electronic Devices , Biosensing Techniques/instrumentation , Sweat/chemistry , Platinum/chemistry , Humans , Catalysis , Glucose/analysis , Graphite/chemistry , Electrochemical Techniques/instrumentation , Nanotubes/chemistry , Limit of Detection , Equipment Design , Oxides/chemistry
2.
Anal Chem ; 96(18): 6930-6939, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38652001

ABSTRACT

Circulating tumor DNA (ctDNA) holds great promise as a noninvasive biomarker for cancer diagnosis, treatment, and prognosis. However, the accurate and specific quantification of low-abundance ctDNA in serum remains a significant challenge. This study introduced, for the first time, a novel exponential amplification reaction (EXPAR)-assisted CRISPR/Cas12a-mediated ratiometric dual-signal electrochemical biosensor for ultrasensitive and reliable detection of ctDNA. To implement the dual-signal strategy, a signal unit (ssDNA-MB@Fc/UiO-66-NH2) was prepared, consisting of methylene blue-modified ssDNA as the biogate to encapsulate ferrocene signal molecules within UiO-66-NH2 nanocarriers. The presence of target ctDNA KRAS triggered EXPAR amplification, generating numerous activators for Cas12a activation, resulting in the cleavage of ssDNA-P fully complementary to the ssDNA-MB biogate. Due to the inability to form a rigid structure dsDNA (ssDNA-MB/ssDNA-P), the separation of ssDNA-MB biogate from the UiO-66-NH2 surface was hindered by electrostatic interactions. Consequently, the supernatant collected after centrifugation exhibited either no or only a weak presence of Fc and MB signal molecules. Conversely, in the absence of the target ctDNA, the ssDNA-MB biogate was open, leading to the leakage of Fc signal molecules. This clever ratiometric strategy with Cas12a as the "connector", reflecting the concentration of ctDNA KRAS based on the ratio of the current intensities of the two electroactive signal molecules, enhanced detection sensitivity by at least 60-300 times compared to single-signal strategies. Moreover, this strategy demonstrated satisfactory performance in ctDNA detection in complex human serum, highlighting its potential for cancer diagnosis.


Subject(s)
Biosensing Techniques , Circulating Tumor DNA , Electrochemical Techniques , Humans , Circulating Tumor DNA/blood , Circulating Tumor DNA/genetics , CRISPR-Cas Systems/genetics , DNA, Single-Stranded/chemistry , Limit of Detection , Endodeoxyribonucleases/chemistry , Proto-Oncogene Proteins p21(ras)/genetics , CRISPR-Associated Proteins/chemistry , Bacterial Proteins/chemistry , Bacterial Proteins/genetics
3.
Anal Chem ; 96(12): 4774-4782, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38477105

ABSTRACT

Circulating tumor DNA (ctDNA), as a next-generation tumor marker, enables early screening and monitoring of cancer through noninvasive testing. Exploring the development of new methods for ctDNA detection is an intriguing study. In this work, a unique electrochemical biosensor for the ctDNA detector was constructed in the first utilizing Fe single-atom nanozymes-carbon dots (SA Fe-CDs) as a signaling carrier in collaboration with a DNA walker cascade amplification strategy triggered by nucleic acid exonuclease III (Exo III). The electrochemical active surface area of AuNPs/rGO modified onto a glassy carbon electrode (AuNPs/rGO/GCE) was about 1.43 times that of a bare electrode (bare GCE), with good electrical conductivity alongside a high heterogeneous electron transfer rate (5.81 × 10-3 cm s-1), that is, as well as the ability to load more molecules. Sequentially, the DNA walker cascade amplification strategy driven by Exo III effectively converted the target ctDNA into an amplified biosignal, ensuring the sensitivity and specificity of ctDNA. Ultimately, the electrochemical signal was further amplified by introducing SA Fe-CDs nanozymes, which could serve as catalysts for 3,3',5,5'-tetramethylbenzidine (TMB) oxidation with facile responding (Vmax = 0.854 × 10-6 M s-1) and robust annexation (Km = 0.0069 mM). The integration of the triple signal amplification approach achieved detection limits as low as 1.26 aM (S/N = 3) for a linearity spanning from 5 aM to 50 nM. In this regard, our proposal for a biosensor with exceptional assay properties in complicated serum environments had great potential for early and timely diagnosis of cancer.


Subject(s)
Biosensing Techniques , Circulating Tumor DNA , Exodeoxyribonucleases , Metal Nanoparticles , Neoplasms , Nucleic Acids , Humans , Carbon , Gold/chemistry , Electrochemical Techniques/methods , Limit of Detection , Metal Nanoparticles/chemistry , Biosensing Techniques/methods
4.
Food Chem ; 446: 138770, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38428079

ABSTRACT

Herein, we made 3D MXene-AuNPs by in situ growth of gold nanoparticles (AuNPs) on the surface of MXene by chemical reduction method, and then introduced three sulfhydryl (-SH) compounds as functionalized modifiers attached to the AuNPs to form a highly selective composite material for the detection of Pb2+, Cu2+, and Hg2+, respectively. The doping of AuNPs changes the microstructure of 2D MXene and generates more active sites. On a sensing platform based on ITO array electrodes, the detection system was optimised with sensitivities up to 1.157, 0.846 and 0.799 µA·µg-1Lcm-2 (Pb2+, Cu2+, and Hg2+). The selectivity of MXene@AuNPs was effectively improved by sulfhydryl group modification. In the range of 1-1300 µg L-1, the detection limits of three ions were 0.07, 0.13 and 0.21 µg L-1. In addition, this method can efficiently and accurately detect heavy metal ions in four cereal samples with consistent results with inductively coupled plasma mass spectrometry.


Subject(s)
Mercury , Metal Nanoparticles , Nitrites , Transition Elements , Gold/chemistry , Lead , Edible Grain/chemistry , Metal Nanoparticles/chemistry , Mercury/analysis , Sulfhydryl Compounds/chemistry , Ions/chemistry
5.
Anal Chim Acta ; 1299: 342441, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38499429

ABSTRACT

BACKGROUND: In health assessment and personalized medical services, accurate detection of biological markers such as dopamine (DA) and uric acid (UA) in sweat is crucial for providing valuable physiological information. However, there are challenges in detecting sweat biomarkers due to their low concentrations, variations in sweat yield among individuals, and the need for efficient sweat collection. RESULTS: We synthesized CuNi-MOF@rGO as a high-activity electrocatalyst and investigated its feasibility and electrochemical mechanism for simultaneously detecting low-concentration biomarkers UA and DA. Interaction between the non-coordinating carboxylate group and the sample produces effective separation signals for DA and UA. The wearable biomimetic biosensor has a wide linear range of 1-500 µM, with a detection limit of 9.41 µM and sensitivity of 0.019 µA µM-1 cm-2 for DA, and 10-1000 µM, with a detection limit of 9.09 µM and sensitivity of 0.026 µA µM-1 cm-2 for UA. Thus, our sensor performs excellently in detecting low-concentration biomarkers. To improve sweat collection, we designed a microfluidic-controlled device with hydrophilic modification in the microchannel. Experimental results show optimal ink flow at 2% concentration. Overall, we developed an innovative and highly active electrocatalyst, successfully enabling simultaneous detection of low-concentration biomarkers UA and DA. SIGNIFICANCE: This study provides a strategy for sweat analysis and health monitoring. Moreover, the sensor also showed good performance in detecting real sweat samples. This study has shown great potential in future advances in sweat analysis and health monitoring.


Subject(s)
Biosensing Techniques , Wearable Electronic Devices , Humans , Sweat/chemistry , Dopamine/analysis , Uric Acid/analysis , Biosensing Techniques/methods , Biomarkers , Electrochemical Techniques
6.
Biosens Bioelectron ; 249: 116012, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38232450

ABSTRACT

The development of wearable devices shows great application potential in health management. In this work, we propose the fabrication of a novel wearable electrochemical patch and prove its application in sweat metabolites detection. The patch is developed based on iron nano-catalysts incorporated laser-induced graphene (FeNCs/LIG), which is a newly integrated sensing electrode with unique three-dimensional nanostructure and good electrocatalytic activity. It shows desirable sensing performances for sweat metabolites including tyrosine (Tyr) and uric acid (UA) molecules. The detection limit of Tyr and UA can reach 5.11 µM and 1.37 µM, respectively. Besides, density functional theory calculation deeply reveals that the Fe active sites of FeNCs play an important role in molecule adsorption and electron transference, thus promoting sensing performance. To realize wearable application, a dual-channel hydrogel chip is designed and assembled with FeNCs/LIG. The developed patch is successfully utilized to accurately determination of Tyr and UA in sweat. This work is expected to provide a new non-invasive strategy for evaluating amino acid intake and metabolic level.


Subject(s)
Biosensing Techniques , Graphite , Wearable Electronic Devices , Biosensing Techniques/methods , Sweat/chemistry , Graphite/chemistry , Electrodes
7.
Anal Chim Acta ; 1289: 342155, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38245196

ABSTRACT

Using an assemble-able MOF material, we successfully constructed an ultra-sensitive electrochemical sensor based on Bi2CuO4@Al-MOF@UiO-67 nanocomposite material, in order to investigate the adsorption properties of the Bi2CuO4@Al-MOF@UiO-67 functional material on the heavy metal ion. The Cd2+, Cu2+, Pb2+ and Hg2+ can be detected at the same time. Selective recognition and enrichment of various metal ions on different substrates can be achieved through the assembly of a large number of Al-MOF and UiO-67-MOF nanomaterial composites with small particle sizes on the Bi2CuO4 surface. Based on this, a new type of sensor is researched and prepared, which has been shown to have good stability and reproducibility. Due to its unique assembly structure, large active surface area, excellent adsorption capacity, and high electrical conductivity, Bi2CuO4@Al-MOF@UiO-67 presents outstanding performance. In addition, the sensor also exhibits excellent electrocatalytic redox capacity and high selectivity. The adsorption capacity of Cd2+, Cu2+, Pb2+ and Hg2+ is also significantly improved under the action of the sensor electrode, however, this is not the case. The limits of detection for Cd2+, Cu2+, Pb2+ and Hg2+ were found to be 0.02 pM, 0.032 pM, 0.018 pM and 0.041 pM, respectively. In order to investigate the detection mechanism of Cd2+, Cu2+, Pb2+ and Hg2+ was adsorption properties as well as electrochemical accumulation of Bi2CuO4@Al-MOF@UiO-67 on the metal atoms were investigated. This method has been successfully applied to samples of rice, sorghum, maize, milk, honey, and tea, and has enabled the simultaneous detection of Cd2+, Cu2+, Pb2+ and Hg2+, which is of significant practical value.


Subject(s)
Mercury , Metal-Organic Frameworks , Metals, Heavy , Nanocomposites , Cadmium/chemistry , Reproducibility of Results , Lead , Nanocomposites/chemistry , Ions
8.
Am J Hematol ; 99(3): 380-386, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38258329

ABSTRACT

Acute myeloid leukemia (AML) in older patients has a poor prognosis, low complete remission (CR) rates, and poor overall survival (OS). Preclinical studies have shown synergistic effects of epigenetic priming with hypomethylating agents followed by cytarabine. Based on these data, we hypothesized that an induction regimen using epigenetic priming with decitabine, followed by cytarabine would be effective and safe in older patients with previously untreated AML. Here, we conducted a phase 2 trial in which older patients with previously untreated AML received an induction regimen consisting of 1 or 2 courses of decitabine 20 mg/m2 intravenously (IV) for 5 days followed by cytarabine 100 mg/m2 continuous IV infusion for 5 days. Forty-four patients (median age 76 years) were enrolled, and CR/CRi was achieved by 26 patients (59% of all patients, 66.7% of evaluable patients). Fourteen of 21 (66.7%) patients with adverse cytogenetics achieved CR including six out of seven evaluable patients with TP53 mutations. The 4- and 8-week mortality rates were 2.3% and 9.1%, respectively, with median OS of 10.7 months. These results suggest epigenetic priming with decitabine followed by cytarabine should be considered as an option for first-line therapy in older patients with AML. This trial was registered at www.clinicaltrials.gov as # NCT01829503.


Subject(s)
Cytarabine , Leukemia, Myeloid, Acute , Aged , Humans , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Decitabine , Epigenesis, Genetic , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Remission Induction , Treatment Outcome
9.
Anal Bioanal Chem ; 415(27): 6647-6661, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37848579

ABSTRACT

Detection of human-generated volatile organic compounds (VOCs) is a new pathway for assessing health. Herein, a polyvinylidene fluoride (PVDF)-based colorimetric sensor array was designed for detecting disease-related VOCs (DVOCs) within 15 min, using a complex of Cu metal-organic framework, graphene aerogel, and dyes as response materials. Fingermaps derived from 28 DVOCs were obtained for further data processing. Pattern recognition was successfully employed in the correct discrimination of 28 DVOCs in low (10 µM), medium (100 µM), and high (300 µM) concentrations. Importantly, the sensor array also presented excellent discrimination ability and application potential when detecting VOCs produced by human cancer and normal cells. In general, VOC acquisition is noninvasive and harmless, and the PVDF-based sensor arrays are simple and visual. Such advantages expand their further application potential.


Subject(s)
Neoplasms , Volatile Organic Compounds , Humans , Colorimetry , Polyvinyls , Neoplasms/diagnosis
10.
ACS Appl Mater Interfaces ; 15(37): 43541-43549, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37694575

ABSTRACT

Resting sweat analysis could provide unique insight into the metabolic levels of physiological and pathological states. However, the low secretion rate of resting sweat and the low concentration of metabolic molecules pose challenges for the development of noninvasive wearable sensors. Here, we demonstrated a wearable patch for the precise analysis of uric acid at rest. Fe single-atom nanozymes (FeSAs) with excellent electrocatalytic activity were used to develop a sensor for selective catalysis of uric acid (UA, 1-425 µM), and the catalytic mechanism of UA was later explored by density functional theory. In addition, polyaniline was integrated into the wearable patch for pH detection; thus, accurate analysis of sweat UA molecules can be achieved by pH calibration. Then, we explored the possibility of collecting resting sweat with different ratios of agarose hydrogels to reduce the sweat accumulation time. Finally, the possibility of a wearable patch for accurate UA detection in volunteer sweat samples was experimentally verified. We believe that our work provides novel insights and ideas for the analysis of resting sweat using wearable devices, further driving advancements in the field of personalized medicine.


Subject(s)
Hydrogels , Wearable Electronic Devices , Humans , Uric Acid , Calibration , Catalysis
11.
Target Oncol ; 18(5): 727-734, 2023 09.
Article in English | MEDLINE | ID: mdl-37728835

ABSTRACT

BACKGROUND: Despite recent approvals of lifesaving treatments for chronic lymphocytic leukemia (CLL), real-world data on the tolerability of the Bruton tyrosine kinase inhibitor ibrutinib for CLL treatment are lacking, especially in Black patients. OBJECTIVE: To expand upon a previously reported retrospective chart review of ibrutinib-treated patients with CLL to increase the number of sites and the enrollment period in first-line (1L) and relapsed/refractory (R/R) settings with a subanalysis based on ethnicity. PATIENTS AND METHODS: Adults with CLL who initiated ibrutinib treatment from five centers were followed for ≥ 6 months. RESULTS: We identified 482 patients with CLL [405 White (153 1L, 252 R/R), 37 Black (17 1L, 20 R/R), 40 other/unidentified]. At baseline, 58.5% of all patients (68.8% of Black patients) had hypertension. At a median follow-up of 28.2 months, 31.1% of patients overall discontinued ibrutinib, 16.2% due to adverse events (12.2% 1L, 18.8% R/R). Overall, 46.0% of patients experienced ≥ 1 dose hold (40.2% 1L, 49.8% R/R), and 28.8% of patients experienced ≥ 1 dose reduction (24.9% 1L, 31.4% R/R). Among Black patients, ibrutinib was discontinued in 24.3% of patients (17.6% 1L, 30.0% R/R), 8.1% due to disease progression and 5.4% due to adverse events; 40.5% of patients experienced ≥ 1 dose hold (35.3% 1L, 45.0% R/R), and 32.4% of patients experienced ≥ 1 dose reduction (23.5% 1L, 40.0% R/R). CONCLUSIONS: Toxicity and disease progression were the most common reasons for ibrutinib discontinuations in the overall population and among Black patients, respectively. Encouraging research participation of underrepresented patient groups will help clinicians better understand treatment outcomes.


Ibrutinib, a Bruton tyrosine kinase inhibitor, is an approved oral targeted therapy for the treatment of chronic lymphocytic leukemia (CLL). Patients treated with ibrutinib can experience side effects (referred to as adverse events) and may need to reduce the drug dose (referred to as dose reductions) or stop treatment (referred to as discontinuations) for a variety of reasons. A previous study showed that patients who were treated with ibrutinib experienced frequent dose reductions and discontinuations. This study described dose reductions and discontinuations in a larger patient population treated with ibrutinib and also described outcomes in Black patients. Patients with CLL treated with ibrutinib were identified from five medical centers and were followed for a minimum of 6 months. Patients experienced frequent dose reductions and discontinuations in routine clinical practice. The most common cause of discontinuations was adverse events in the overall patient population and disease progression in the Black patient population. Black patients treated with ibrutinib had similar rates of dose reductions and discontinuations as the overall patient population. Rates of dose reductions and discontinuations for patients with CLL treated with ibrutinib were higher in this real-world study than in clinical trials.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Adult , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Race Factors , Retrospective Studies , Disease Progression
12.
Blood Adv ; 7(22): 7141-7150, 2023 11 28.
Article in English | MEDLINE | ID: mdl-37722354

ABSTRACT

The phase 3 SELENE study evaluated ibrutinib + chemoimmunotherapy (CIT; bendamustine and rituximab [BR]; or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]) for patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Adult patients who had received ≥1 prior line of CIT were randomized 1:1 to oral ibrutinib (560 mg) or placebo daily, plus 6 cycles of BR/R-CHOP. The primary end point was investigator-assessed progression-free survival (PFS). Overall, 403 patients were randomized to ibrutinib + CIT (n = 202) or placebo + CIT (n = 201). Most patients received BR (90.3%) and had FL (86.1%). With a median follow-up of 84 months, median PFS was 40.5 months in the ibrutinib + CIT arm and 23.8 months in the placebo + CIT arm (hazard ratio [HR], 0.806; 95% confidence interval [CI], 0.626-1.037; P = .0922). Median overall survival was not reached in either arm (HR, 0.980; 95% CI, 0.686-1.400). Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 85.6% and 75.4% of patients in the ibrutinib + CIT and placebo + CIT arms, respectively. In each arm, 13 patients had TEAEs leading to death. The addition of ibrutinib to CIT did not significantly improve PFS compared with placebo + CIT. The safety profile was consistent with known profiles of ibrutinib and CIT. This trial was registered at www.clinicaltrials.gov as #NCT01974440.


Subject(s)
Lymphoma, B-Cell, Marginal Zone , Lymphoma, Follicular , Adult , Humans , Rituximab/adverse effects , Bendamustine Hydrochloride/therapeutic use , Piperidines/therapeutic use , Vincristine/adverse effects , Cyclophosphamide/adverse effects , Prednisone/adverse effects , Doxorubicin/adverse effects , Lymphoma, B-Cell, Marginal Zone/drug therapy , Lymphoma, Follicular/drug therapy
13.
Anal Chem ; 95(32): 12122-12130, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37527175

ABSTRACT

Accurate detection of cancer-associated mRNAs is beneficial to early diagnosis and potential treatment of cancer. Herein, for the first time, we developed a novel CRISPR/Cas12a-powered electrochemical/fluorescent (EC/FL) dual-mode controlled-release homogeneous biosensor for mRNA detection. A functionalized ssDNA P2-capped Fe3O4-NH2 loaded with methylene blue (P2@MB-Fe3O4-NH2) was synthesized as the signal probe, while survivin mRNA was chosen as the target RNA. In the presence of the target mRNA, the nicking endonuclease-mediated rolling circle amplification (NEM-RCA) was triggered to produce significant amounts of ssDNA, activating the collateral activity of Cas12a toward the surrounding single-stranded DNA. Thus, the ssDNA P1 completely complementary to ssDNA P2 was cleaved, resulting in that the ssDNA P2 bio-gate on Fe3O4-NH2 could not be opened due to electrostatic interactions. As a result, there was no or only a little MB in the supernatant after magnetic separation, and the measured EC/FL signal was exceedingly weak. On the contrary, the ssDNA P2 bio-gate was opened, enabling MB to be released into the supernatant, and generating an obvious EC/FL signal. Benefiting from the accuracy of EC/FL dual-mode cross-verification, high amplification efficiency, high specificity of NEM-RCA and CRISPR/Cas12a, and high loading of mesoporous Fe3O4-NH2 on signal molecules, the strategy shows aM-level sensitivity and single-base mismatch specificity. More importantly, the practical applicability of this dual-mode strategy was confirmed by mRNA quantification in complex serum environments and tumor cell lysates, providing a new way for developing a powerful disease diagnosis tool.


Subject(s)
Biosensing Techniques , CRISPR-Cas Systems , CRISPR-Cas Systems/genetics , Delayed-Action Preparations , RNA, Messenger/genetics , RNA , Coloring Agents , DNA, Single-Stranded/genetics , Endonucleases , Serine Proteinase Inhibitors
14.
Bioelectrochemistry ; 154: 108542, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37591183

ABSTRACT

An ultra-sensitive ratiometric electrochemical aptasensor was constructed based on metal-organic frameworks (MOFs) and bimetallic oxides for the detection of the human epidermal growth factor receptor 2 (HER2), a breast cancer marker. The aluminum metal-organic framework (Al-MOF) and cerium-metal-organic framework (Ce-MOF) have higher specific surface area, which is conducive to load more aptamers or complementary DNA (cDNA), and realize the amplification of internal reference signal Fc. Furthermore, nanoflower-like bismuth copper oxide (Bi2CuO4) with abundant active sites was introduced to modify more aptamers on its surface, which were then fixed to the glassy carbon electrode (GCE) to amplify the detection signal. The quantitative detection of HER2 was achieved by differential pulse voltammetry (DPV), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The materials were characterized by scanning electron microscope, transmission electron microscope, Zeta potential analyzer, X-ray diffraction and X-ray photoelectron spectroscopy. The ratiometric electrochemical aptasensor based on nanomaterial and chain displacement signal amplification technology could discern HER2 in a very wide range (0.001-20.0 ng/mL) with an extremely low detection limit (0.049 pg/mL) and has demonstrated good performance in clinical serum analysis. This strategy also provides a feasible idea for sensitive analysis of other clinical tumor markers.


Subject(s)
Metal-Organic Frameworks , Humans , Receptor, ErbB-2 , Biomarkers, Tumor
15.
Anal Chim Acta ; 1276: 341642, 2023 Oct 02.
Article in English | MEDLINE | ID: mdl-37573120

ABSTRACT

Herein, an ultrasensitive electrochemical biosensor for microRNA-155 (miR-155) detection based on the powerful catalytic and continuous walking signal amplification capability of 3D DNAzyme walker and the gold nanoparticles/graphene aerogels carbon fiber paper-based (AuNPs/GAs/CFP) flexible sensing electrode with excellent electrochemical performance was successfully constructed. In a proof-of-concept experiment, in the presence of miR-155, the DNAzyme strands anchored on the streptavidin-modified magnetic beads (MBs) silenced by locked strands can be activated, thus generating the walking arm of the 3D DNAzyme walker. Meanwhile, the substrate strands modified with Fe-MOF-NH2 nanoparticles were evenly distributed on the surface of MBs and served as tracks of the 3D DNAzyme walker. Once the DNAzyme strand was activated, the catalytic site in the substrate strand can be cleaved in the presence of Mn2+, and a large number of stumps modified with Fe-MOF-NH2 nanoparticles (output@Fe-MOF-NH2) will be generated during the continuous and efficient walking cleavage of the DNAzyme walker, driving the recognition-catalysis-release cycle process for signal amplification. Immediately afterwards, the signal was read out through the base complementary pairing of capture probe (PS) immobilized on the surface of the paper-based flexible sensing electrode AuNPs/GAs/CFP and signal probes output@Fe-MOF-NH2, thus achieving the quantitative detection of miR-155. Under optimal experimental conditions, the designed 3D DNAzyme walker-based biosensor exhibited a relatively lower limit of detection (LOD) of 56.23 aM, with a linear range of 100 aM to 100 nM. Overall, the proposed 3D DNAzyme walker biosensor exhibited good interference and reproducibility, demonstrating a promising future in the field of clinical disease diagnosis.


Subject(s)
Biosensing Techniques , DNA, Catalytic , Metal Nanoparticles , MicroRNAs , Gold , Reproducibility of Results , Electrochemical Techniques , Limit of Detection
16.
Hematol Oncol ; 41(4): 743-752, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37086447

ABSTRACT

Relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) is a genetically complex and heterogeneous disease with a poor prognosis and limited treatment options. Thus, there is an urgent need to develop therapeutic combinations to overcome drug resistance in AML. This open-label, multicenter, international, phase 1b study evaluated the safety, efficacy, and pharmacokinetics of venetoclax in combination with alvocidib in patients with R/R AML. Patients were treated with escalating doses of venetoclax (400, 600, and 800 mg QD, orally, days 1-28) and alvocidib (45 and 60 mg/m2 , intravenously, days 1-3) in 28-day cycles. The combination was found to be safe and tolerable, with no maximum tolerated dose reached. Drug-related Grade ≥3 adverse events were reported in 23 (65.7%) for venetoclax and 24 (68.6%) for alvocidib. No drug-related AEs were fatal. Gastrointestinal toxicities, including diarrhea, nausea, and vomiting were notable and frequent; otherwise, the toxicities reported were consistent with the safety profile of both agents. The response rate was modest (complete remission [CR] + incomplete CR [CRi], 11.4%; CR + CRi + partial response rate + morphologic leukemia-free state, 20%). There was no change in alvocidib pharmacokinetics with increasing doses of venetoclax. However, when venetoclax was administered with alvocidib, AUC24 and Cmax decreased by 18% and 19%, respectively. A recommended phase 2 dose was not established due to lack of meaningful increase in efficacy across all cohorts compared to what was previously observed with each agent alone. Future studies could consider the role of the sequence, dosing, and the use of a more selective MCL1 inhibitor for the R/R AML population.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Leukemia, Myeloid, Acute , Humans , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/etiology
18.
Appl Opt ; 62(6): A127-A136, 2023 Feb 20.
Article in English | MEDLINE | ID: mdl-36821331

ABSTRACT

Trace detection of toxic heavy metals is a very important and difficult problem in several areas: convenience, sensitivity, and reliability. Herein, we develop an innovative fluorescence resonance energy transfer (FRET)-based ratio fluorescence sensor for the detection of heavy metal mercury ion (H g 2+). The sensing platform is composed of coumarin derivatives (CDs) and a copper metal-organic framework (Cu-MOF) named CD/Cu-MOF. The constructed CD/Cu-MOFs ratio fluorescence sensor exhibits dual emission peaks at 430 and 505 nm under the single excitation wavelength of 330 nm. With the addition of H g 2+, the fluorescence intensity of the system at 430 nm gradually increased, and the fluorescence intensity at 505 nm remained stable, resulting in a change in the fluorescence ratio. There is a good logarithmic relationship between the H g 2+ concentration in the range from 2×10-8 to 0.001 nM and the ratio of the fluorescence emission intensity of the system (F 430/F 505) (R 2=0.9901), and its calculated detection limit is 3.76×10-9 n M. In addition, the CD/Cu-MOFs ratio fluorescence sensor has achieved a good recovery rate of standard addition in the actual food sample recovery experiment, which provides an effective method for the detection of H g 2+ in food samples.

19.
Talanta ; 256: 124294, 2023 May 01.
Article in English | MEDLINE | ID: mdl-36696736

ABSTRACT

Herein, we developed a unique screen-printed carbon electrode (SPCE) with three-dimensional melamine-doped graphene oxide/MXene composite aerogel (3D MGMA) modification, which is used for the simultaneous and sensitive detection of three metal ions (Zn2+, Cd2+, and Pb2+) in the environment. A self-assembly method was used to fabricate 3D MXene aerogels based on MXene, graphene oxide (GO), and melamine. Notably, the network-like 3D structure combining 2D MXene and rGO sheets can provide a high ratio of surface area and enriched functional clusters, which are beneficial for improving the electrical conductivity and promoting the uptake of heavy metal ions. In the linear range of 3-900 µg L-1, the constructed innovative sensing platform can sensitively detect Zn2+, Cd2+, and Pb2+ simultaneously, with detection limits of 0.48 µg L-1,0.45 µg L-1 and 0.29 µg L-1 respectively. This work reflects precision and reliability in the detection of three water samples (tap water, Minzhu lake and Yangtze River) and four cereal samples (sorghum, rice, wheat and corn), proposing a novel strategy for monitoring heavy metal ions in the natural environment.

20.
Anal Chim Acta ; 1281: 341867, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-38783733

ABSTRACT

Efficient catalytic decomposition of H2O2 is accompanied by electron transfer through Fe-Nx active sites of hemin in the human body. Inspired by this reaction process, the Fe SAs/Co CNs were successfully synthesized by combined Co atomic sites with nitrogen-carbon doped Fe single-atom active sites (SAs). The synergy between transition metals not only reduces agglomeration during synthesis but also improves its own electrical conductivity due to the interaction between Fe and Co that promotes the formation of graphite surface. Crucially, the synergistic effect of the Co site significantly enhanced the peroxidase activity of the Fe SAs and the reaction rate of the Fenton-like reaction, resulting in an efficient detection of H2O2. Catalytic kinetic calculations and enzymatic kinetic calculations were used to verify the electron transfer rate and catalytic performance of their constructed electrochemical sensing interfaces. The results showed that Fe SAs/Co CNs@GCE showed better detection performance than Fe SAs CNs@GCE. It was applied successfully to detect H2O2 released from cells in real-time as well. The linear detection range of Fe SAs/Co CNs@GCE for H2O2 was 1-16664 µM, and the detection limit was as low as 0.25 µM. Furthermore, an electrochemical sensing chip was constructed using Fe SAs/Co CNs@SPE and the prepared microfluidic channel. The constructed portable FeSAs/Co CNs@SPE had a linear range of 1-400 µM and a detection limit of 0.36 µM and achieved the recovery detection of H2O2 in serum. The electrochemical sensing interfaces constructed based on Fe SAs/Co CNs all have efficient catalytic performance and excellent real-time hydrogen peroxide detection performance, which have practical application potential for human oxidative stress level detection. And it provides a novel approach to the trace detection of bioactive small molecules.


Subject(s)
Cobalt , Electrochemical Techniques , Hydrogen Peroxide , Iron , Limit of Detection , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/analysis , Electrochemical Techniques/methods , Cobalt/chemistry , Iron/chemistry , Humans , Catalysis
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