Association between adductor pollicis muscle thickness and low skeletal muscle mass index in community-dwelling older women undergoing outpatient rehabilitation.

OBJECTIVE: The performance of sarcopenia diagnosis using adductor pollicis muscle thickness (APMT) has been reported. However, the relationship between APMT and low skeletal muscle mass index (SMI) is unclear. The purpose of this study is to investigate the relationship between APMT and low SMI and APMT performance to diagnose low SMI in community-dwelling older women undergoing outpatient rehabilitation. METHODS: This study included 65 older women (mean age: 86.4 years). Subjects were received outpatient rehabilitation one to three times a week. The main outcomes were low SMI as diagnosed using the Asian working group for sarcopenia 2019 and APMT. Logistic regression analysis was performed with low SMI as the dependent variable, APMT, and propensity score calculated using age, sex, number of medications, and updated Charlson comorbidity index as the independent variable. A receiver operating characteristic (ROC) curve of APMT for low SMI was created. A cut-off value was calculated using the Youden index. RESULTS: Among the 65 subjects, 45 (69.2 %) had low SMI. The results of the logistic regression analysis showed a significant association between APMT and low SMI (odds ratio: 0.482 {95 % confidence interval [CI]: 0.313-0.744}). The cut-off value of APMT calculated from the ROC curve was 13 mm. The sensitivity and specificity of this cut-off value were 0.800 (95 % CI: 0.654-0.904) (36 out of 45 subjects) and 0.850 (95 % CI: 0.621-0.968) (17 out of 20 subjects), respectively. The positive predictive value, negative predictive value, and area under the curve were 0.923 (95 % CI: 0.791-0.984), 0.654 (95 % CI: 0.443-0.828), and 0.843 (95 % CI: 0.731-0.955), respectively. The APMT cut-off value of 13 mm is good to identify low SMI. CONCLUSIONS: The results of this study show that APMT is associated with low SMI. Furthermore, the cut-off value of APMT for diagnosing low SMI was 13 mm. The APMT cut-off value of 13 mm is good to identify low SMI. Our findings indicate that measuring APMT is useful for diagnosing low SMI in community-dwelling older women undergoing outpatient rehabilitation.

Urinary prostanoids are elevated by anti-TNF and anti-IL6 receptor disease-modifying antirheumatic drugs but are not predictive of response to treatment in early rheumatoid arthritis.

BACKGROUND: Disease-modifying antirheumatic drugs (DMARDs) are widely used for treating rheumatoid arthritis (RA). However, there are no established biomarkers to predict a patient's response to these therapies. Prostanoids, encompassing prostaglandins, prostacyclins, and thromboxanes, are potent lipid mediators implicated in RA progression. Nevertheless, the influence of DMARDs on prostanoid biosynthesis in RA patients remains poorly understood. This study aims to assess the impact of various DMARDs on urinary prostanoids levels and to explore whether urinary prostanoid profiles correlate with disease activity or response to therapy. METHODS: This study included 152 Swedish female patients with early RA, all rheumatoid factor (RF) positive, enrolled in the NORD-STAR trial (registration number: NCT01491815). Participants were randomized into four therapeutic regimes: methotrexate (MTX) combined with (i) prednisolone (arm ACT), (ii) TNF-α blocker certolizumab pegol (arm CZP), (iii) CTLA-4Ig abatacept (arm ABA), or (iv) IL-6R blocker tocilizumab (arm TCZ). Urine samples, collected before start of treatment and at 24 weeks post-treatment, were analyzed for tetranor-prostaglandin E metabolite (tPGEM), tetranor-prostaglandin D metabolite (tPGDM), 2,3-dinor thromboxane B2 (TXBM), 2,3-dinor-6-keto prostaglandin F1a (PGIM), leukotriene E4 (LTE4) and 12-hydroxyeicosatetraenoic acid (12-HETE) using liquid chromatography-mass spectrometry (LC-MS). Generalized estimating equation (GEE) models were used to analyze the change in urinary eicosanoids and their correlations to clinical outcomes. RESULTS: Patients receiving MTX combined with CZP or TCZ exhibited significant elevations in urinary tPGEM and TXBM levels after 24 weeks of treatment. Other eicosanoids did not show significant alterations in response to any treatment. Baseline urinary eicosanoid levels did not correlate with baseline clinical disease activity index (CDAI) levels, nor with changes in CDAI from baseline to week 24. Their levels were also similar between patients who achieved CDAI remission and those with active disease at week 24. CONCLUSIONS: Treatment with anti-TNF or anti-IL6R agents in early RA patients leads to an increased systemic production of proinflammatory and prothrombotic prostanoids. However, urinary eicosanoid levels do not appear to be predictive of the response to DMARDs therapy.

Associations of per- and polyfluoroalkyl substances (PFAS) and their mixture with oxidative stress biomarkers during pregnancy.

BACKGROUND: Oxidative stress from excess reactive oxygen species (ROS) is a hypothesized contributor to preterm birth. Per- and polyfluoroalkyl substances (PFAS) exposure is reported to generate ROS in laboratory settings, and is linked to adverse birth outcomes globally. However, to our knowledge, the relationship between PFAS and oxidative stress has not been examined in the context of human pregnancy. OBJECTIVE: To investigate the associations between prenatal PFAS exposure and oxidative stress biomarkers among pregnant people. METHODS: Our analytic sample included 428 participants enrolled in the Illinois Kids Development Study and Chemicals In Our Bodies prospective birth cohorts between 2014 and 2019. Twelve PFAS were measured in second trimester serum. We focused on seven PFAS that were detected in >65 % of participants. Urinary levels of 8-isoprostane-prostaglandin-F2α, prostaglandin-F2α, 2,3-dinor-8-iso-PGF2α, and 2,3-dinor-5,6-dihydro-8-iso-PGF2α were measured in the second and third trimesters as biomarkers of oxidative stress. We fit linear mixed-effects models to estimate individual associations between PFAS and oxidative stress biomarkers. We used quantile g-computation and Bayesian kernel machine regression (BKMR) to assess associations between the PFAS mixture and averaged oxidative stress biomarkers. RESULTS: Linear mixed-effects models showed that an interquartile range increase in perfluorooctane sulfonic acid (PFOS) was associated with an increase in 8-isoprostane-prostaglandin-F2α (ß = 0.10, 95 % confidence interval = 0, 0.20). In both quantile g-computation and BKMR, and across all oxidative stress biomarkers, PFOS contributed the most to the overall mixture effect. The six remaining PFAS were not significantly associated with changes in oxidative stress biomarkers. CONCLUSIONS: Our study is the first to investigate the relationship between PFAS exposure and biomarkers of oxidative stress during human pregnancy. We found that PFOS was associated with elevated levels of oxidative stress, which is consistent with prior work in animal models and cell lines. Future research is needed to understand how prenatal PFAS exposure and maternal oxidative stress may affect fetal development.

Study of bypassing Microsoft Windows Security using the MITRE CALDERA Framework.

Background: Microsoft Windows Security is a recently implemented safeguard for the Windows operating systems, including the latest versions of Windows10 and 11. However, there is a major shortcoming in this system to stop Advanced Persistent Threat (APT). These are government-financed groups that are funded to attack other government entities. Following the initial security breach, the hacked Windows device is used to access the rest of the network devices in order to transfer data to external storage (Exfiltration). Methods: In this work, we have tested the Microsoft Windows Security system using MITRE CALDERA and ATT&CK frameworks and explain how APT groups are able to bypass Windows Security. Results: In this study we used "54ndc47" agent through GoLang feature in MITRE CALDERA platform to test and bypass Microsoft Windows Security systems (MS Windows 10). Through it, we were able to bypass the Windows Security system and display entire files in the victim's device. Conclusions: In this paper, we have provided recommendations to Microsoft to improve their Windows Security tool through the use of Artificial intelligence (AI).

Dual-mode photoelectrochemical/electrochemical sensor based on Z-scheme AgBr/AgI-Ag-CNTs and aptamer structure switch for the determination of kanamycin.

A "signal-on" dual-mode aptasensor based on photoelectrochemical (PEC) and electrochemical (EC) signals was established for kanamycin (Kana) assay by using a novel Z-scheme AgBr/AgI-Ag-CNTs composite as sensing platform, an aptamer structure switch, and K3[Fe(CN)6] as photoelectron acceptor and electrochemical signal indicator. The aptamer structure switch was designed to obtain a "signal-off" state, which included an extended Kana aptamer (APT), one immobilized probe (P1), and one blocking probe (P2) covalently linked with graphdiyne oxide (GDYO) nanosheets. P1, P2, and aptamer formed the double helix structure, which resulted in the inhibited photocurrent intensity because of the weak conductivity of double helix layer and serious electrostatic repulsion of GDYO towards K3[Fe(CN)6]. In the presence of Kana, APT specifically bound to the target and dissociated from P1 and P2, and thus, a "signal-on" state was initiated by releasing P2-GDYO from the platform. Based on the sensing platform and the aptamer structure switch, the dual-mode aptasensor realized the linear determination ranges of 1.0 pM-2.0 µM with a detection limit (LOD) of 0.4 pM (for PEC method) and 10 pM-5.0 µM with a LOD of 5 pM (for EC method). The aptasensor displayed good application potential for Kana test in real samples.

Translocation of Specific DNA Nanocarrier through an Ultrasmall Nanopipette: Toward Single-Protein-Molecule Detection with Superior Signal-to-Noise Ratio.

The use of functional DNA nanostructures as carriers to ship proteins through solid-state nanopores has recently seen substantial growth in single-protein-molecule detection (SPMD), driven by the potential of this methodology and implementations that it may enable. Ultrasmall nanopores have exhibited obvious advantages in spatiotemporal biological detection due to the appropriate nanoconfined spaces and unique properties. Herein, a 6.8 nm DNA tetrahedron (TDN) with a target-specific DNA aptamer (TDN-apt) was engineered to carry the representative target of acetylcholinesterase (AChE) through an ultrasmall nanopipet with a 30 nm orifice, underpinning the advanced SPMD of AChE with good performance in terms of high selectivity, low detection limit (0.1 fM), and especially superior signal-to-noise ratio (SNR). The kinetic interaction between TDN-apt and AChE was studied and the practical applicability of the as-developed SPMD toward real samples was validated using serum samples from patients with Alzheimer's disease. This work not only presented a feasible SPMD solution toward low-abundance proteins in complex samples and but also was envisioned to inspire more interest in the design and implementation of synergized DNA nanostructure-ultrasmall nanopore systems for future SPMD development.

A self-assembled bilayer polypeptide-engineered hydrogel for spatiotemporal modulation of bactericidal and anti-inflammation process in osteomyelitis treatment.

BACKGROUND: Drug resistance of pathogens and immunosuppression are the main causes of clinical stagnation of osteomyelitis. The ideal treatment strategy for osteomyelitis is to achieve both efficient antibacterial and bone healing through spatiotemporal modulation of immune microenvironment. METHODS: In this study, a bilayer hydrogel based on genetically engineered polypeptide AC10A and AC10ARGD was prepared by self-assembly. Ag2S QDs@DSPE-mPEG2000-Ce6/Aptamer (AD-Ce6/Apt) was loaded in the top layer AC10A hydrogel (AA) for antibacterial, and bone marrow-derived mesenchymal stem cells (BMSCs) were loaded in the lower layer AC10ARGD hydrogel (MAR) for bone healing. The AD-Ce6/Apt can be released from the AA hydrogel to target S. aureus before bacterial biofilm formation and achieved significant bactericidal effect under irradiation with a 660 nm laser. Moreover, AD-Ce6/Apt can induce M1 type polarization of macrophages to activate the immune system and eliminate residual bacteria. Subsequently, BMSCs released from the MAR hydrogel can differentiate into osteoblasts and promote the formation of an anti-inflammatory microenvironment by regulating the M2 type polarization of macrophages. The bilayer AA-MAR hydrogel possessed good biocompatibility. RESULTS: The in vitro and in vivo results showed that the AA-MAR hydrogel not only realized efficient photodynamic therapy of S. aureus infection, but also promoted the transformation of immune microenvironment to fulfill the different needs of each stage, which ultimately improved bone regeneration and mechanical properties post-surgery. CONCLUSION: This work presents an approach for spatiotemporal modulation of immune microenvironment in the treatment of osteomyelitis.

Abbreviated Antiplatelet Therapy After Coronary Stenting in Patients With Myocardial Infarction at High Bleeding Risk.

BACKGROUND: The optimal duration of antiplatelet therapy (APT) after coronary stenting in patients at high bleeding risk (HBR) presenting with an acute coronary syndrome remains unclear. OBJECTIVES: The objective of this study was to investigate the safety and efficacy of an abbreviated APT regimen after coronary stenting in an HBR population presenting with acute or recent myocardial infarction. METHODS: In the MASTER DAPT trial, 4,579 patients at HBR were randomized after 1 month of dual APT (DAPT) to abbreviated (DAPT stopped and 11 months single APT or 5 months in patients with oral anticoagulants) or nonabbreviated APT (DAPT for minimum 3 months) strategies. Randomization was stratified by acute or recent myocardial infarction at index procedure. Coprimary outcomes at 335 days after randomization were net adverse clinical outcomes events (NACE); major adverse cardiac and cerebral events (MACCE); and type 2, 3, or 5 Bleeding Academic Research Consortium bleeding. RESULTS: NACE and MACCE did not differ with abbreviated vs nonabbreviated APT regimens in patients with an acute or recent myocardial infarction (n = 1,780; HR: 0.83; 95% CI: 0.61-1.12 and HR: 0.86; 95% CI: 0.62-1.19, respectively) or without an acute or recent myocardial infarction (n = 2,799; HR: 1.03; 95% CI: 0.77-1.38 and HR: 1.13; 95% CI: 0.80-1.59; Pinteraction = 0.31 and 0.25, respectively). Bleeding Academic Research Consortium 2, 3, or 5 bleeding was significantly reduced in patients with or without an acute or recent myocardial infarction (HR: 0.65; 95% CI: 0.46-0.91 and HR: 0.71; 95% CI: 0.54-0.92; Pinteraction = 0.72) with abbreviated APT. CONCLUSIONS: A 1-month DAPT strategy in patients with HBR presenting with an acute or recent myocardial infarction results in similar NACE and MACCE rates and reduces bleedings compared with a nonabbreviated DAPT strategy. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).

Colorimetric biosensor for visual determination of Golgi protein 73 based on reduced graphene oxide-carboxymethyl chitosan-Hemin/platinum@palladium nanozyme with peroxidase-like activity.

A Golgi protein 73 (GP73) colorimetric biosensor based on the reduced graphene oxide-carboxymethyl chitosan-hemin/platinum@palladium nanoparticles (RGO-CMCS-Hemin/Pt@Pd NPs) with peroxidase-like activity was constructed. The RGO-CMCS-Hemin/Pt@Pd NPs with high peroxidase-like activity were successfully synthesized under mild conditions. Then, the aminylated GP73 aptamer (Apt) was bound to the RGO-CMCS-Hemin/Pt@Pd NPs to form the recognition probe. Another unmodified GP73 aptamer (AptI) was served as the capture probe. In the presence of target GP73, the capture probe and the recognition probe specifically bind to GP73 and form a RGO-CMCS-Hemin/Pt@Pd NP-Apt/GP73/AptI sandwich-type structure, which can oxidase the colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxTMB in the presence of H2O2. GP73 detection was achieved by measuring the peak UV absorption at 652 nm. Under the optimum conditions, the GP73 concentration was linearly related to the absorbance intensity in the range 10.0-110.0 ng/mL, and the limit of detection (LOD) was 4.7 ng/mL. The proposed colorimetric biosensor was successfully applied to detect GP73 in spiked human serum samples with recoveries of 98.2-107.0% and RSDs of 1.90-5.44%, demonstrating the excellent potential for highly sensitive GP73 detection in clinical detection. A colorimetric biosensor for visual determination of GP73 based on RGO-CMCS-Hemin/Pt@Pd NPs nanozyme with peroxidase-like activity was designed. The GP73 biosensor responses linearly from 10.0-110.0 ng/mL with LOD of 4.7 ng/mL, and shows acceptable specificity and good recovery.

Quasi-steady-state amide proton transfer (QUASS APT) MRI enhances pH-weighted imaging of acute stroke.

PURPOSE: Chemical exchange saturation transfer (CEST) imaging measurement depends not only on the labile proton concentration and pH-dependent exchange rate but also on experimental conditions, including the relaxation delay and radiofrequency (RF) saturation time. Our study aimed to extend a quasi-steady-state (QUASS) solution to a modified multi-slice CEST MRI sequence and test if it provides enhanced pH imaging after acute stroke. METHODS: Our study derived the QUASS solution for a modified multislice CEST MRI sequence with an unevenly segmented RF saturation between image readout and signal averaging. Numerical simulation was performed to test if the generalized QUASS solution corrects the impact of insufficiently long relaxation delay, primary and secondary saturation times, and multi-slice readout. In addition, multiparametric MRI scans were obtained after middle cerebral artery occlusion, including relaxation and CEST Z-spectrum, to evaluate the performance of QUASS CEST MRI in a rodent acute stroke model. We also performed Lorentzian fitting to isolate multi-pool CEST contributions. RESULTS: The QUASS analysis enhanced pH-weighted magnetization transfer asymmetry contrast over the routine apparent CEST measurements in both contralateral normal (-3.46% ± 0.62% (apparent) vs. -3.67% ± 0.66% (QUASS), P < 0.05) and ischemic tissue (-5.53% ± 0.68% (apparent) vs. -5.94% ± 0.73% (QUASS), P < 0.05). Lorentzian fitting also showed significant differences between routine and QUASS analysis of ischemia-induced changes in magnetization transfer, amide, amine, guanidyl CEST, and nuclear Overhauser enhancement (-1.6 parts per million) effects. CONCLUSION: Our study demonstrated that generalized QUASS analysis enhanced pH MRI contrast and improved quantification of the underlying CEST contrast mechanism, promising for further in vivo applications.

Aptamer/Hydroxyapatite-Functionalized Titanium Substrate Promotes Implant Osseointegration via Recruiting Mesenchymal Stem Cells.

Endowing bone regeneration materials with both stem cell recruitment and osteoinduction properties is a key factor in promoting osseointegration of titanium (Ti) implants. In this study, Apt19s-grafted oxidized hyaluronic acid (OHA) was deposited onto a protein-mediated biomineralization hydroxyapatite (HAp) coating of Ti. HAp was achieved by the treatment of lysozyme and tris(2-carboxyethyl) phosphonate mixture and then soaked in calcium ion (Ca2+) solution to obtain functional Ti substrate (Ti/HAp/OHA-Apt). In vitro studies confirmed that Ti/HAp/OHA-Apt could effectively maintain the sustained release of Apt19s from Ti for 7 days. The released Apt19s significantly enhanced the migration of bone marrow mesenchymal stem cells (MSCs), which was reflected by the experiment of transwell assay, wound healing, and zymogram detection. Compared with pure Ti, Ti/HAp/OHA-Apt was able to adjust the adsorption of functional proteins at the Ti-based interface to expose their active sites, which significantly increased the expression of adhesion-associated proteins (vinculin and tensin) in MSCs to promote their adhesion on Ti-based interface. In vitro cell experiments of alkaline phosphatase activity staining, mineralization detection, and expression of osteogenesis-related genes showed that Ti/HAp/OHA-Apt significantly enhanced the osteogenic differentiation ability of MSCs, which may be highly related to the porous structure of hydroxyapatite on Ti interface. In vivo test of Micro-CT, H&E staining, and histochemical staining further confirmed that Ti/HAp/OHA-Apt was able to promote MSC recruitment at the peri-implant interface to form new bone. This work provides a new approach to develop functional Ti-based materials for bone defect repair.

Aptamer-Gold Nanocage Composite for Photoactivated Immunotherapy.

Immune checkpoint blockade (ICB) has been hailed as the hope for conquering cancer as ICB could produce a significant and durable response to tumor cells. However, the high cost and severe side effects of ICB drugs limited their application for further anticancer therapy. Here, we developed a photoactivated immunotherapy nanoplatform (Apt@AuNC). This nanoplatform could target tumor tissues via enhanced penetration retention (EPR) effect and the aptamer (Apt) could be released from Apt@AuNC in tumor sites via illumination. The immune system in the tumor area was then activated after the combination of Apt and PD-1 protein. The heat generated from AuNC was able to continue killing tumor cells. This nanoplatform could not only achieve the precise immunotherapy but also significantly facilitate the anticancer efficacy.

Detection of prostate cancer biomarkers via a SERS-based aptasensor.

The overexpression of specific biomarkers in serum is closely related to diseases, and accurate and sensitive detection of them is beneficial for the early diagnosis and treatment of cancer. In this study, we developed a novel surface-enhanced Raman spectroscopy (SERS)-based aptasensor to detect the prostate-specific antigen biomarkers, consisting of total prostate-specific antigen (PSA) and free prostate-specific antigen (f-PSA). A composite structure containing arrays of polystyrene colloidal sphere @Ag shell (PS@Ag) was fabricated as a SERS-active chip. A complementary DNA probe (SH-DNA) and PSA aptamer (Apt) were immobilised stepwise on the chip, followed by the binding of a Raman reporter methylene blue (MB) to the guanine base of the aptamer. PSA-Apt recognition causes the release of MB-Apt and a decrease in the SERS intensity of MB on the chip, which correlates with the PSA concentration. The proposed biosensor has high spectral reproducibility, selectivity, and sensitivity and successfully determines the PSA levels in serum samples collected from prostate cancer patients, demonstrating great potential for clinical diagnosis.

Clopidogrel versus ticagrelor in East Asian patients aged 75 years or older with acute coronary syndrome: observations from the GF-APT registry.

The benefits of potent antithrombotic therapy usually come at the expense of a higher risk of bleeding. The efficacy and safety of ticagrelor in elderly East Asian populations remains debated due to the concerns about the imbalance of ischemic and bleeding risks. This study aimed to compare the impact of clopidogrel with ticagrelor on clinical outcomes in East Asian patients aged ≥75 years with acute coronary syndrome (ACS) using data from an institutional registry. We assessed the treatment effect of ticagrelor versus clopidogrel based on propensity scores and multivariate Cox proportional hazards models. A total of 2775 ACS patients were included, of which 235 (8.5%) were treated with ticagrelor. The primary efficacy outcome occurred in 11.9% of patients treated with ticagrelor versus 8.8% treated with clopidogrel. There was no significant association between treatment with ticagrelor and a lower risk of the primary efficacy outcome (p = .156). However, the incidences of all-cause death (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.02 to 2.79) and major bleeding (adjusted HR 2.20, 95% CI 1.06 to 4.56) were significantly higher in patients treated with ticagrelor than clopidogrel. In elderly patients with ACS from East Asia, the efficacy of clopidogrel was comparable to ticagrelor, while ticagrelor is associated with an increased risk of mortality and major bleeding.

What is the context?Current guidelines recommend ticagrelor over clopidogrel for patients with acute coronary syndrome (ACS).There are no specific guidelines concerning the elderly, and data on optimal antiplatelet therapy in elderly are quite scarce.Further study was necessary to identify the efficacy and safety of ticagrelor and clopidogrel in elderly patients from East Asian populations which are reported to be at a higher risk of bleeding.What is new?The risk of major adverse cardiac events did not differ significantly between clopidogrel versus ticagrelor in patients aged ≥75 years from East Asia, while the use of ticagrelor might be associated with increased risk of mortality and major bleeding events.Analyses after propensity score matching showed consistent results on the safety and efficacy of clopidogrel versus ticagrelor.The benefit of potent P2Y₁₂ inhibitor ticagrelor over clopidogrel is questionable in elderly East Asian patients with ACS.What is the impact? This study provides more information on the use of potent antiplatelet therapy in older patients from Asia. The individual assessment of ischemic and bleeding risk is necessary to guide decision-making on DAPT rather than applying the recommendations of guidelines directly.

Developing a robust method integrating with selective membrane-based preconcentration and signal amplification for field virus detection.

Infectious diseases caused by viruses have attracted global concern owing to their rapid spread and catastrophic consequences. Therefore, developing fast and reliable on-site virus detection methods is essential for the prevention and treatment of virus-related diseases. In this study, immunoassays on a membrane, combining virus preconcentration with nanoparticle-based signal amplification, were used to realize the rapid and accurate visual detection of viruses. The biotin-streptavidin scaffolds for target virus preconcentration were established on a membrane, and subsequently a Zika aptamer (Apt) immobilized on the membrane recognized and captured the nonstructural protein 1 of Zika virus (ZIKV-NS1). The probe for detection was synthesized by conjugating the Zika Apt with a high level of horseradish peroxidase on gold nanoparticles. The ZIKV-loaded membrane was incubated with the probes, and the viral signal was amplified as the signal of horseradish peroxidase. In the presence of 3,3,5',5'-tetramethyl benzidine and hydrogen peroxide, the green color of the probe-coated membrane indicated the level of ZIKV-NS1. Our developed method could reach a detection limit of 5 ng mL-1, and the whole procedure could be completed within 1 h. Analyses of rabbit serum and environmental water samples demonstrated that an immunoassay-based approach on the membrane could accurately determine the level of ZIKV-NS1 against the complicated matrix. Our results suggest that this virus detection method has a high potential for application in clinical and environmental settings.

A universal monoclonal antibody-aptamer conjugation strategy for selective non-invasive bioparticle isolation from blood on a regenerative microfluidic platform.

Simultaneous isolation of various circulating tumor cell (CTC) subtypes from whole blood is useful in cancer diagnosis and prognosis. Microfluidic affinity separation devices are promising for CTC separation because of their high throughput capacity and automatability. However, current affinity agents, such as antibodies (mAbs) and aptamers (Apts) alone, are still suboptimal for efficient, consistent, and versatile cell analysis. By introducing a hybrid affinity agent, i.e., an aptamer-antibody (Apt-mAb) conjugate, we developed a universal and regenerative microchip with high efficiency and non-invasiveness in the separation and profiling of various CTCs from blood. The Apt-mAb conjugate consists of a monoclonal antibody that specifically binds the target cell receptor and a surface-bound aptamer that recognizes the conserved Fc region of the mAb. The aptamer then indirectly links the surface functionalization of the microfluidic channels to the mAbs. This hybrid affinity agent and the microchip platform may be widely useful for various bio-particle separations in different biological matrices. Further, the regeneration capability of the microchip improves data consistency between multiple uses and minimizes plastic waste while promoting environmental sustainability. STATEMENT OF SIGNIFICANCE: A hybrid affinity agent, Apt-mAb, consisting of a universal aptamer (Apt) that binds the conserved Fc region of monoclonal antibodies (mAbs) was developed. The invented nano-biomaterial combines the strengths and overcomes the weakness of both Apts and mAbs, thus changing the paradigm of affinity separation of cell subtypes. When Apt-mAb was used to fabricate microfluidic chips using a "universal screwdriver" approach, the microchip could be easily tuned to bind any cell type, exhibiting great universality. Besides high sensitivity and selectivity, the superior regenerative capacity of the microchips makes them reusable, which provides improved consistency and repeatability in cell profiling and opens a new approach towards in vitro diagnostic point-of-care testing devices with environmental sustainability and cost-effectiveness.

Electrochemical aptasensor based on the target-induced strand displacement strategy-driven for T-2 toxin detection.

Herein, an aptasensor based on target-induced strand displacement (TISD) strategy was developed for sensitive detection of T-2 toxin. Gold nanoparticles@ aminated manganese dioxide (AuNPs@NH2-MnO2) exhibited excellent electrical conductivity and provided more binding sites for aptamer (Apt). Besides, polyethyleneimine-reduced graphene oxide/gold­platinum core-shell nanorods composites (PEI-rGO/Pt@Au NRs) were used to be carriers for signaling tags, as their sufficiently large specific surface area improved the loading capacity for signal molecules. In the presence of T-2, the Apt sequence was more inclined to form an Apt-T-2 complex, and the cDNA was displaced from the Apt-cDNA duplex, while the signal tag was released, resulting in a weakened MB signal, differential pulse voltammetry (DPV) was used to record the signal change. Under optimal conditions, the signal response of the constructed electrochemical aptasensor exhibited a good linear relationship with the concentration of T-2. The detection limit was 8.74 × 10-7 ng mL-1over a wide range of concentration from 5 × 10-6 ng mL-1 to 5 ng mL-1. Furthermore, the proposed aptasensor had excellent specificity, good stability and can be well applied to the detection of real samples. It provided a new avenue for the research and development of sensitive aptasensors in food detection and analysis.

The feasibility of amide proton transfer imaging at 3 T for bladder cancer: a preliminary study.

AIM: To investigate the optimal amide proton transfer (APT) imaging parameters for bladder cancer (BCa), the influence of different protein concentrations and pH values on APT imaging, and to establish the reliability of APT imaging in healthy volunteers and patients with BCa. MATERIALS AND METHODS: The optimal APT imaging parameters for BCa were experimentally optimised using cross-linked bovine serum albumin (BSA) phantoms. BSA phantoms were scanned with different values for the saturation power, saturation duration and number of excitations. Meanwhile, BSA phantoms containing different protein concentrations and solutions of different pH levels were scanned. The interobserver agreement of the asymmetric magnetisation transfer ratio (MTRasym) was assessed in 11 healthy volunteers and 18 patients with BCa. RESULTS: The optimal scanning scheme consisted of 1 excitation, a saturation power of 2 µT, and a saturation time of 2 s. The APT signal intensity increased as the protein concentration increased and as the pH decreased. The MTRasym showed good concordance for all subjects. The MTRasym of BCa tissue was significantly higher (1.81 ± 0.71) than that of bladder wall in healthy volunteers (0.34 ± 0.12) and normal bladder wall in patients with BCa (0.31 ± 0.11; p<0.001). There was no significant difference between the bladder wall of healthy volunteers and the normal bladder wall of patients with BCa. CONCLUSION: APT imaging showed potential value for application in BCa.

Mediators of inflammation resolution and vasoactive eicosanoids in gestational diabetes and preeclampsia.

OBJECTIVE: Women with gestational diabetes (GDM) have an increased risk of preeclampsia and postpartum diabetes. Inflammation associates with both GDM and preeclampsia. This study examined specialized proresolving mediators (SPM) that direct inflammation resolution and eicosanoids that are involved in inflammation, in relation to the development of preeclampsia and ongoing postpartum glucose intolerance in GDM. METHODS: Participants were selected from a prospective study examining the development of preeclampsia in women with GDM. Four groups of age-matched women were studied: GDM ( n  = 20), GDM who developed preeclampsia (GDM+PE, n  = 21), GDM who remained glucose-intolerant postpartum (GDM+PPIGT, n  = 20), or pregnancies with glucose tolerance within the normal range (NGT, n  = 21). Measurement of SPM (E-series resolvins and D-series resolvins), SPM pathway intermediates (14-HDHA, 18-HEPE and 17-HDHA), 20-hydroxyeicosatetraenoic acid (20-HETE), and the urinary metabolite of the vasodilator prostacyclin 2,3-dinor-6-Keto-PGF 1α , were made at 28, 32 and 36 weeks gestation and at 6 months postpartum. RESULTS: Compared with GDM, GDM+PE had elevated levels of 20-HETE and the SPM pathway intermediates 14-HDHA, 18-HEPE, 17-HDHA, at 32 weeks, and the SPM RvE1 at 32 and 36 weeks gestation. Compared with NGT and regardless of whether they developed preeclampsia or PPIGT, GDM had lower levels of 2,3-dinor-6-Keto-PGF 1α during pregnancy. CONCLUSION: Reduced levels of the prostacyclin metabolite 2,3-dinor-6-Keto-PGF 1α may contribute to the increased risk of preeclampsia in women with GDM. The increase in 20-HETE, a vasoconstrictor and mediator of inflammation, and SPM that contribute to inflammation resolution, prior to the onset of preeclampsia require further investigation to clarify their clinical significance.

Nanozyme-mediated signal amplification for ultrasensitive photoelectrochemical sensing of Staphylococcus aureus based on Cu-C3N4-TiO2 heterostructure.

Food-borne pathogens are one of the leading causes of food poisoning, which vigorously affect food safety and human health. Therefore, the development of early and rapid detection methods for food pollution evaluation is the key to food safety and quality control. Herein, a simple and inexpensive photoelectrochemical (PEC) sensor is developed for highly selective and ultrasensitive detection of Staphylococcus aureus (S. aureus). The technique is based on "signal-off" that employs Cu-C3N4-TiO2 heterostructures as photoactive materials and monolayer Cu-C3N4 nanozyme as a signal amplifier. In the presence of S. aureus, the aptamer-modified Cu-C3N4 (Cu-C3N4@Apt, a signal amplifier) and S. aureus were specifically anchored on the surface of the ligand-modified photoelectrode. The Cu-C3N4@Apt nanozyme acted as a peroxidase to catalyze the oxidation of 4-chloro-1-naphthol (4-CN) to produce insoluble precipitate on the electrode surface and resulted in a significant decrease in photocurrent. Based on the signal-amplification by the Cu-C3N4@Apt nanozyme, the constructed PEC sensor demonstrated a wide linear range between 10-108 CFU/mL for the S. aureus detection with the detection limit (LOD) as low as 3.40 CFU/mL. Furthermore, the PEC sensor was capable of determining S. aureus in spiked orange juice and milk, with the recovery of 91%-113%, indicating the reliability of the sensor for S. aureus detection in real samples. This investigation provides a feasible strategy for the design of highly selective and ultrasensitive PEC sensors to determine analytes in complex systems.