Lab-in-a-Vial Rapid Test for Internet of Things-Embedded Point-of-Healthcare Protein Biomarker Detection in Bodily Fluids.

Amateurs often struggle with detecting and quantifying protein biomarkers in body fluids due to the high expertise required. This study introduces a Lab-in-a-Vial (LV) rapid diagnostic platform, featuring hydrangea-like platinum nanozymes (PtNH), for rapid, accurate detection and quantification of protein biomarkers on-site within 15 min. This method significantly enhances detection sensitivity for various biomarkers in body fluids, surpassing traditional methods such as enzyme-linked immunosorbent assays (ELISA) and lateral flow assays (LFA) by ≈250 to 1300 times. The LV platform uses a glass vial coated with specific bioreceptors such as antigens or antibodies, enabling rapid in vitro evaluation of disease risk from small fluid samples, similar to a personal ELISA-like point-of-care test (POCT). It overcomes challenges in on-site biomarker detection, allowing both detection and quantification through a portable wireless spectrometer for healthcare internet of things (H-IoT). The platform's effectiveness and adaptability are confirmed using IgG/IgM antibodies from SARS-CoV-2 infected patients and nuclear matrix protein (NMP22) from urothelial carcinoma (UC) patients as biomarkers. These tests demonstrated its accuracy and flexibility. This approach offers vast potential for diverse disease applications, provided that the relevant protein biomarkers in bodily fluids are identified.

Dual antibody-aided mesoporous nanoreactor for H2O2 self-supplying chemodynamic therapy and checkpoint blockade immunotherapy in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) represents a formidable challenge due to the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, rendering it unresponsive to conventional hormonal and targeted therapies. This study introduces the development of mesoporous nanoreactors (NRs), specifically mPDA@CuO2 NRs, as acid-triggered agents capable of self-supplying H2O2 for chemodynamic therapy (CDT). To enhance therapeutic efficacy, these NRs were further modified with immune checkpoint antagonists, specifically anti-PD-L1 and anti-CD24 antibodies, resulting in the formation of dual antibody-aided mesoporous nanoreactors (dAbPD-L1/CD24-mPDA@CuO2 NRs). These NRs were designed to combine CDT and checkpoint blockade immunotherapy (CBIT) for precise targeting of 4T1 TNBC cells. Remarkably, dAbPD-L1/CD24-mPDA@CuO2 NRs exhibited tumor-targeted CDT triggered by H2O2 and successfully activated immune cells including T cells and macrophages. This integrated approach led to a remarkable inhibition of tumor growth by leveraging the collaborative effects of the therapies. The findings of this study introduce a novel and promising strategy for the integrative and collaborative treatment of refractory cancers, providing valuable insights into addressing the challenges posed by aggressive breast cancer, particularly TNBC.

Prognostic significance of positive surgical margins for scalp angiosarcoma.

BACKGROUND: Scalp angiosarcomas (AS) are aggressive soft tissue sarcomas that present with outcomes different from other AS of the head and neck region. Due to the rarity of the disease, limited data on the clinical outcome of scalp AS are available. In particular, the prognostic significance of surgical margins remains controversial and the impact of margin status on survival has not been documented. METHODS: We retrospectively reviewed 41 scalp AS patients, including 30 patients with localized disease and 11 patients with initial distant metastasis, treated in our institution between 1997 and 2017. Survival was determined by Kaplan-Meier analysis. In the 30 patients without distant metastasis (localized disease), univariate and multivariate analysis using the Cox proportional hazards model were used to determine clinicopathologic characteristics associated with recurrence free survival (RFS), locoregional control (LRC), and overall survival (OS). RESULTS: Totally 41 patients diagnosed with scalp AS were identified, including 30 patients with localized disease and 11 patients with initial distant metastasis on diagnosis. Overall, the median follow-up period was 19.3 (range 0.3-128.5) months. The median survival time was 16.6 (range 0.3-144.3) months and the 5-year OS (95% Confidence Interval (CI)) rate was 22% (12%-42%). In the 30 patients with localized disease, univariate analysis showed that positive margins, either lateral-side or deep-side, were significant prognostic factors for RFS, LRC, and OS (p < 0.05). On multivariate analysis, positive margins emerged as adverse prognostic factors for RFS (Hazard Ratio (HR) 4.29, 95% CI, 1.71-10.75, p = 0.002), LRC (HR 6.35, 95% CI, 2.19-18.37, p = 0.001), and OS (HR 4.73, 95% CI, 1.71-13.07, p = 0.003). CONCLUSION: Scalp AS is associated with high local recurrence rates and poor survival outcomes. Positive surgical margins are adverse prognostic factors for survival.

Maternal Adenine-Induced Chronic Kidney Disease Programs Hypertension in Adult Male Rat Offspring: Implications of Nitric Oxide and Gut Microbiome Derived Metabolites.

Maternal chronic kidney disease (CKD) during pregnancy causes adverse fetal programming. Nitric oxide (NO) deficiency, gut microbiota dysbiosis, and dysregulated renin-angiotensin system (RAS) during pregnancy are linked to the development of hypertension in adult offspring. We examined whether maternal adenine-induced CKD can program hypertension and kidney disease in adult male offspring. We also aimed to identify potential mechanisms, including alterations of gut microbiota composition, increased trimethylamine-N-oxide (TMAO), reduced NO bioavailability, and dysregulation of the RAS. To construct a maternal CKD model, female Sprague-Dawley rats received regular chow (control group) or chow supplemented with 0.5% adenine (CKD group) for 3 weeks before pregnancy. Mother rats were sacrificed on gestational day 21 to analyze placentas and fetuses. Male offspring (n = 8/group) were sacrificed at 12 weeks of age. Adenine-fed rats developed renal dysfunction, glomerular and tubulointerstitial damage, hypertension, placental abnormalities, and reduced fetal weights. Additionally, maternal adenine-induced CKD caused hypertension and renal hypertrophy in adult male offspring. These adverse pregnancy and offspring outcomes are associated with alterations of gut microbiota composition, increased uremic toxin asymmetric and symmetric dimethylarginine (ADMA and SDMA), increased microbiota-derived uremic toxin TMAO, reduced microbiota-derived metabolite acetate and butyrate levels, and dysregulation of the intrarenal RAS. Our results indicated that adenine-induced maternal CKD could be an appropriate model for studying uremia-related adverse pregnancy and offspring outcomes. Targeting NO pathway, microbiota metabolite TMAO, and the RAS might be potential therapeutic strategies to improve maternal CKD-induced adverse pregnancy and offspring outcomes.

Direct glucose detection in whole blood by colorimetric assay based on glucose oxidase-conjugated graphene oxide/MnO2 nanozymes.

We herein report a facile approach for the preparation of horseradish peroxidase (HRP)-mimic glucose oxidase-conjugated graphene oxide/MnO2 (GOD-GO/MnO2) as new nanozyme to detect the glucose concentration in whole blood. The nano-sized of MnO2 nanoparticles embedded in bovine serum albumin (BSA)-coated GO by in situ growth were evaluated focusing on the principle of HRP-mimic activity catalyzing the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide. Furthermore, we constructed dual sensing platforms based on the combination of a plasma separation pad and GOD-GO/MnO2 for direct detection of glucose concentration in whole blood by colorimetric assay without blood sample pretreatment. As a proof-of-concept, a limit of detection of 3.1 mg dL-1 for glucose was obtained with a wide linear quantification range from 25 mg dL-1 to 300 mg dL-1 through visual observation and quantitative analysis, suggesting potential clinical applications in blood glucose monitoring for diabetic patients.

Functional RNAs: combined assembly and packaging in VLPs.

We describe here a one pot RNA production, packaging and delivery system based on bacteriophage Qß. We demonstrate a method for production of a novel RNAi scaffold, packaged within Qß virus-like particles (VLPs). The RNAi scaffold is a general utility chimera that contains a functional RNA duplex with paired silencing and carrier sequences stabilized by a miR-30 stem-loop. The Qß hairpin on the 5΄ end confers affinity for the Qß coat protein (CP). Silencing sequences can include mature miRNAs and siRNAs, and can target essentially any desired mRNA. The VLP-RNAi assembles upon co-expression of CP and the RNAi scaffold in E. coli. The annealing of the scaffold to form functional RNAs is intramolecular and is therefore robust and concentration independent. We demonstrate dose- and time-dependent inhibition of GFP expression in human cells with VLP-RNAi. In addition, we target the 3΄UTR of oncogenic Ras mRNA and suppress Pan-Ras expression, which attenuates cell proliferation and promotes mortality of brain tumor cells. This combination of RNAi scaffold design with Qß VLP packaging is demonstrated to be target-specific and efficient.

Magnetic-composite-modified polycrystalline silicon nanowire field-effect transistor for vascular endothelial growth factor detection and cancer diagnosis.

This study proposes a vascular endothelial growth factor (VEGF) biosensor for diagnosing various stages of cervical carcinoma. In addition, VEGF concentrations at various stages of cancer therapy are determined and compared to data obtained by computed tomography (CT) and cancer antigen 125 (CA-125). The increase in VEGF concentrations during operations offers useful insight into dosage timing during cancer therapy. This biosensor uses Avastin as the biorecognition element for the potential cancer biomarker VEGF and is based on a n-type polycrystalline silicon nanowire field-effect transistor (poly-SiNW-FET). Magnetic nanoparticles with poly[aniline-co-N-(1-one-butyric acid) aniline]-Fe3O4 (SPAnH-Fe3O4) shell-core structures are used as carriers for Avastin loading and provide rapid purification due to their magnetic properties, which prevent the loss of bioactivity; furthermore, the high surface area of these structures increases the quantity of Avastin immobilized. Average concentrations in human blood for species that interfere with detection specificity are also evaluated. The detection range of the biosensor for serum samples covers the results expected from both healthy individuals and cancer patients.

AI-Driven Design System for Fabrication of Inhalable Nanocatchers for Virus Capture and Neutralization.

The global pandemic presents a critical threat to humanity, with no effective rapid-response solutions for early-stage virus dissemination. This study aims to create an AI-driven entry-blocker design system (AIEB) to fabricate inhalable virus-like nanocatchers (VLNCs) fused with entry-blocking peptides (EBPs) to counter pandemic viruses and explore therapeutic applications. This work focuses on developing angiotensin-converting enzyme 2 (ACE2)-mimic domain-fused VLNCs (ACE2@VLNCs) using AIEB and analyzing their interaction with the SARS-CoV-2 receptor binding domain (RBD), demonstrating their potential to hinder SARS-CoV-2 infection. Aerosol-based tests show ACE2@VLNCs persist over 70 min in the air and neutralize pseudoviruses within 30 min, indicating their utility in reducing airborne virus transmission. In vivo results reveal ACE2@VLNCs mitigate over 67% of SARS-CoV-2 infections. Biosafety studies confirm their safety, causing no damage to eyes, skin, lungs, or trachea, and not eliciting significant immune responses. These findings offer crucial insights into pandemic virus prevention and treatment, highlighting the potential of the ACE2@VLNCs system as a promising strategy against future pandemics.

Magnetic resonance monitoring of focused ultrasound/magnetic nanoparticle targeting delivery of therapeutic agents to the brain.

The superparamagnetic properties of magnetic nanoparticles (MNPs) allow them to be guided by an externally positioned magnet and also provide contrast for MRI. However, their therapeutic use in treating CNS pathologies in vivo is limited by insufficient local accumulation and retention resulting from their inability to traverse biological barriers. The combined use of focused ultrasound and magnetic targeting synergistically delivers therapeutic MNPs across the blood-brain barrier to enter the brain both passively and actively. Therapeutic MNPs were characterized and evaluated both in vitro and in vivo, and MRI was used to monitor and quantify their distribution in vivo. The technique could be used in normal brains or in those with tumors, and significantly increased the deposition of therapeutic MNPs in brains with intact or compromised blood-brain barriers. Synergistic targeting and image monitoring are powerful techniques for the delivery of macromolecular chemotherapeutic agents into the CNS under the guidance of MRI.

Design single-stranded DNA aptamer of cluster of differentiation 47 protein by stochastic tunnelling-basin hopping-discrete molecular dynamics method.

The formation of the Cluster of Differentiation 47 (CD47, PDB code: 2JJT)/signal regulatory protein α (SIRPα) complex is very important as it protects healthy cells from immune clearance while promoting macrophage phagocytosis for tumour elimination. Although several antibodies have been developed for cancer therapy, new function-blocking aptamers are still under development. This study aims to design the aptamer AptCD47, which can block the formation of the CD47/SIRPα complex. This study employs the MARTINI coarse-grained (CG) force field and the stochastic tunnelling-basin hopping-discrete molecular dynamics (STUN-BH-DMD) method to identify the most stable AptCD47/CD47 complexes. Coarse-grained molecular dynamics (CGMD) simulations were used to obtain root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) analyses. The results demonstrate that the formation of AptCD47/CD47 complexes renders the CD47 structure more stable than the single CD47 molecule in a water environment. The minimum energy pathway (MEP) obtained by the nudged elastic band (NEB) method indicates that the binding processes of 5'-ATTCAATTCC-3' and 5'-AGTGCAATCT-3' to CD47 are barrierless, which is much lower than the binding barrier of SIRPα to CD47 of about 14.23 kcal/mol. Therefore, these two AptCD47/CD47 complexes can create a high spatial binding barrier for SIRPα, preventing the formation of a stable CD47/SIRPα complex. The proposed numerical process with the MARTINI CG force field can be used to design CD47 aptamers that efficiently block SIRPα from binding to CD47.Communicated by Ramaswamy H. Sarma.

Anti-Hypertensive Property of an NO Nanoparticle in an Adenine-Induced Chronic Kidney Disease Young Rat Model.

Hypertension is the most common complication of chronic kidney disease (CKD) in children but is still poorly controlled. Nitric oxide (NO) deficiency plays a pivotal role in CKD and hypertension. NO is known to have health benefits, while NO typically has a short half-life and is not specifically targeted. In this study, we used a pediatric CKD model, which was induced in young rats by feeding them 0.25% adenine. We investigated two different NO donors, namely S-nitrosoglutathione (GSNO) and diethylenetriamine/NO adduct (DETA NONOate) via intraperitoneal injection at 10 mg/kg/day daily for 3 weeks. GSNO was delivered by Cu2+-doped zeolitic imidazolate framework (Cu/ZIF-8) nanoparticles to generate NO. As a result, we observed Cu/ZIF-8 nanoparticles were successfully loaded with GSNO and were able to release NO. Young rats fed with adenine displayed kidney dysfunction and hypertension at 9 weeks of age, which were prevented by GSNO-loaded nanoparticle or DETA NONOate treatment. GSNO-loaded nanoparticles reduced CKD-induced hypertension, which was related to an enhanced endogenous NO-generating system, reduced renal oxidative stress, and downregulated several components belonging to the classic renin-angiotensin (RAS) system. Our results cast new light on targeting NO delivery through the use of nanoparticles aiming to improve child-focused outcomes related to CKD worthy of clinical translation.

Bioengineered Bacteriophage-Like Nanoparticles as RNAi Therapeutics to Enhance Radiotherapy against Glioblastomas.

Since glioblastomas (GBMs) are radioresistant malignancies and most GBM recurrences occur in radiotherapy, increasing the effectiveness of radiotherapy by gene-silencing has recently attracted attention. However, the difficulty in precisely tuning the composition and RNA loading in nanoparticles leads to batch-to-batch variations of the RNA therapeutics, thus significantly restricting their clinical translation. Here, we bioengineer bacteriophage Qß particles with a designed broccoli light-up three-way junction (b-3WJ) RNA scaffold (contains two siRNA/miRNA sequences and one light-up aptamer) packaging for the silencing of genes in radioresistant GBM cells. The in vitro results demonstrate that the cleavage of de novo designed b-3WJ RNA by Dicer enzyme can be easily monitored in real-time using fluorescence microscopy, and the TrQß@b-3WJLet-7gsiEGFR successfully knocks down EGFR and IKKα simultaneously and thereby inactivates NF-κB signaling to inhibit DNA repair. Delivery of TrQß@b-3WJLet-7gsiEGFR through convection-enhanced delivery (CED) infusion followed by 2Gy X-ray irradiation demonstrated that the median survival was prolonged to over 60 days compared with the 2Gy X-ray irradiated group (median survival: 31 days). Altogether, the results of this study could be critical for the design of RNAi-based genetic therapeutics, and CED infusion serves as a powerful delivery system for promoting radiotherapy against GBMs without evidence of systemic toxicity.

Enhanced therapeutic agent delivery through magnetic resonance imaging-monitored focused ultrasound blood-brain barrier disruption for brain tumor treatment: an overview of the current preclinical status.

Malignant glioma is a severe primary CNS cancer with a high recurrence and mortality rate. The current strategy of surgical debulking combined with radiation therapy or chemotherapy does not provide good prognosis, tumor progression control, or improved patient survival. The blood-brain barrier (BBB) acts as a major obstacle to chemotherapeutic treatment of brain tumors by severely restricting drug delivery into the brain. Because of their high toxicity, chemotherapeutic drugs cannot be administered at sufficient concentrations by conventional delivery methods to significantly improve long-term survival of patients with brain tumors. Temporal disruption of the BBB by microbubble-enhanced focused ultrasound (FUS) exposure can increase CNS-blood permeability, providing a promising new direction to increase the concentration of therapeutic agents in the brain tumor and improve disease control. Under the guidance and monitoring of MR imaging, a brain drug-delivery platform can be developed to control and monitor therapeutic agent distribution and kinetics. The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.

Design the RNA aptamer of PCA3 long non-coding ribonucleic acid by the coarse-grained molecular mechanics.

The stochastic tunneling-basin hopping-discrete molecular dynamics (STUN-BH-DMD) method was applied to predict the tertiary structure of the prostate cancer marker PCA3 using two respective secondary structures predicted by the Vienna RNA package and Mathews lab package. The RNA CG force field with the geometrical restraints for maintaining PCA3 secondary structures is used. For each secondary structure, 5000 PCA3 structures were predicted by using 5000 independent initial structures. These structures were then evaluated by a scoring function, considering the contributions from the radius of gyration, contact energy, and surface fraction of complementary nucleotides to ASO683 and ASO735 used in the related experiment. For each secondary structure, the PCA3 structures with the highest three scores were selected for aptamer design and further adsorption simulation. The ASOs complementary to PCA3 surface segments possessing relatively higher RMSF values are selected to be the potential PCA3 aptamers. After the adsorption simulation, the adsorption energies of ASO961, ASO3181, ASO3533, and ASO3595 are higher than or comparable to those of ASO683 and ASO735 used in the experiment. The NEB method was used to obtain MEPs for the adsorption process of all predicted ASOs onto PCA3. The adsorption barriers range between 29 ∼ 39 kcal/mol, while the desorption barriers range between 112 ∼ 352 kcal/mol, indicating these aptamer/PCA3 complexes are very stable. Using PCA3 surface segments with relatively higher RMSF values, longer ASOs can be also obtained and most longer ASOs possess lower binding energy, ranging between -486.1 and -618.2 kcal/mol.Communicated by Ramaswamy H. Sarma.

Development of a photothermal bead-based nucleic acid amplification test (pbbNAAT) technique for a high-performance loop-mediated isothermal amplification (LAMP)-based point-of-care test (POCT).

We have developed a novel molecular diagnostic platform (photothermal bead-based nucleic acid amplification test; pbbNAAT) that greatly improves the low sensitivity of direct loop-mediated isothermal amplification (LAMP) and allows for specific detection of LAMP amplicons in complex samples. The pbbNAAT integrates specific ligand-functionalized polypyrrole-coated iron oxide particles (PPy@IOs) capable of photothermal conversion and single-molecule magnetic capture of target analytes, the released nucleic acid, and LAMP-amplified products under external light energy control and magnetic manipulations. This allows for sample pretreatment, pbbLAMP amplification, and subsequent amplicon detection with bead-based ELISA in a one-stop microreactor without loss. In addition, photonic heating with PPy@IOs and external light control provide instant and uniform heating for thermolysis and pbbLAMP implementations. Moreover, it generates higher primer annealing stringency for LAMP primers in pbbLAMP; thus, it can detect pathogen-specific DNA accurately and promptly in pathogen-spiked complex materials. The sample pretreatment procedure of pbbNAAT can greatly reduce inhibitors originating from complex samples, which enables the maintenance of maximal enzyme activities for highly sensitive detection. More importantly, the pbbLAMP assay coupled with magnetic capture permits subsequent bead-based ELISA detection to determine true positive LAMP amplicons on PPy@IOs. The pbbNAAT platform has a high tolerance to inhibitors originating from complex samples, high analytical specificity, and limitation of detection (LoD) as low as 8 CFU/reaction to detect E. coli spiked in human whole blood, bovine milk, and can be completed in less than 1 h. Therefore, we believe that pbbNAAT can serve as a suitable direct LAMP platform for on-site POCTs.

Point-of-Care Wound Blotting with Alcian Blue Grading versus Fluorescence Imaging for Biofilm Detection and Predicting 90-Day Healing Outcomes.

Biofilm infection has been identified as a crucial factor of the pathogenesis of chronic wound, but wound biofilm diagnosis remains as an unmet clinical need. We previously proposed a modified wound blotting technique using Alcian blue staining for biofilm detection that was characterized as being non-invasive, time-saving, non-expansive, and informative for biofilm distribution. In this study, we adapted a novel Alcian blue grading method as the severity of biofilm infection for the wound blotting technique and compared its biofilm detection efficacy with MolecuLight i:X- a point-of-care florescence imaging device to detect bacteria and biofilm in wounds. Moreover, their predictive value of complete wound healing at 90 days was analyzed. When validated with wound culture results in the 53 enrolled subjects with chronic wounds, the modified wound blotting method showed a strong association with wound culture, while MolecuLight i:X only exhibited a weak association. In predicting 90-day wound outcomes, the modified wound blotting method showed a strong association (Kendall's tau value = 0.563, p < 0.001), and the wound culture showed a moderate association (Spearman's rho = 0.535, p < 0.001), but MolecuLight i:X exhibited no significant association (p = 0.184). In this study, modified wound blotting with the Alcian blue grading method showed superior value to MolecuLight i:X both in biofilm detection and predictive validity in 90-day wound-healing outcomes.

Sodium Thiosulfate Improves Hypertension in Rats with Adenine-Induced Chronic Kidney Disease.

Hypertension is highly prevalent in chronic kidney disease (CKD). Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter with vasodilator properties. We, hence, investigated whether oral administration of sodium thiosulfate (STS), a clinically applicable H2S-based therapy, can exert a protective effect against hypertension in an adenine-induced CKD rat model. Eight-week-old male Sprague-Dawley rats were fed with 0.5% adenine chow for 3 weeks to induce CKD. After 1 week, the rats were divided into two groups: one without and one with STS (2 g/kg body weight/day) in drinking water for 2 weeks. Treatment with STS lowered systolic and diastolic blood pressure by 7 and 9 mm Hg, respectively. Renal H2S-generating enzyme expression was inhibited by CKD, while STS therapy increased plasma levels of H2S and thiosulfate. Additionally, restoration of nitric oxide bioavailability and rebalance of the renin-angiotensin system may contribute to the protective effects of STS. Our data suggest that the oral administration of STS improves hypertension in an adenine-induced CKD model, which brings us closer to the clinical translation of H2S-targeting therapy in CKD-induced hypertension.

Microneedle patches integrated with lateral flow cassettes for blood-free chronic kidney disease point-of-care testing during a pandemic.

Chronic kidney disease (CKD) is the most neglected chronic disease affecting over 750 million persons in the world. Currently, many patients with cancers or other chronic diseases (i.e., CKD) struggle to receive clinical treatment or examination due to hospitals cancelling or delaying in the COVID-19 pandemic, which may increase the risk of death. Cystatin C (Cys C) has been proposed as a potential glomerular filtration rate (GFR) marker for the early detection of acute kidney injury and CKD. However, most traditional methods for Cys C detection are immunoassays using serum as a sample and are tedious to perform and economically burdensome. To diagnose the disease in the early stage and carry out daily management during the current pandemic, we developed an integration of hydrogel microneedle patch (HMNP) and lateral flow cassette (LFC) to rapidly detect Cys C in skin interstitial fluid (ISF) in 25 min for blood-free CKD management anytime and anywhere by the naked eye that can reduce the impact of an individual's quality of life and life expectancy. Conceivably, this strategy presents a wide scope in the application of numerous other diseases if corresponding analytes are available in skin ISF.

In vivo MR quantification of superparamagnetic iron oxide nanoparticle leakage during low-frequency-ultrasound-induced blood-brain barrier opening in swine.

PURPOSE: To verify that low-frequency planar ultrasound can be used to disrupt the BBB in large animals, and the usefulness of MRI to quantitatively monitor the delivery of superparamagnetic iron oxide (SPIO) nanoparticles into the disrupted regions. MATERIALS AND METHODS: Two groups of swine subjected to craniotomy were sonicated with burst lengths of 30 or 100 ms, and one group of experiment was also performed to confirm the ability of 28-kHz sonication to open the BBB transcranially. SPIO nanoparticles were administered to the animals after BBB disruption. Procedures were monitored by MRI; SPIO concentrations were estimated by relaxivity mapping. RESULTS: Sonication for 30 ms created shallow disruptions near the probe tip; 100-ms sonications after craniotomy can create larger and more penetrating openings, increasing SPIO leakage ∼3.6-fold than 30-ms sonications. However, this was accompanied by off-target effects possibly caused by ultrasonic wave reflection. SPIO concentrations estimated from transverse relaxation rate maps correlated well with direct measurements of SPIO concentration by optical emission spectrometry. We have also shown that transcranial low-frequency 28-kHz sonication can induce secure BBB opening from longitudinal MR image follow up to 7 days. CONCLUSION: This study provides valuable information regarding the use low-frequency ultrasound for BBB disruption and suggest that SPIO nanoparticles has the potential to serve as a thernostic agent in MRI-guided ultrasound-enhanced brain drug delivery.