Integrating Reliable Pt-S Bond-Mediated 3D DNA Nanomachine with Magnetic Separation in a Homogeneous Electrochemical Strategy for Exosomal MicroRNA Detection with Low Background and High Sensitivity.

Precise and sensitive analysis of exosomal microRNA (miRNA) is of great importance for noninvasive early disease diagnosis, but it remains a great challenge to detect exosomal miRNA in human blood samples because of their small size, high sequence homology, and low abundance. Herein, we integrated reliable Pt-S bond-mediated three-dimensional (3D) DNA nanomachine and magnetic separation in a homogeneous electrochemical strategy for the detection of exosomal miRNA with low background and high sensitivity. The 3D DNA nanomachine was easily prepared via a facile and rapid freezing method, and it was capable of resisting the influence of biothiols, thus endowing it with high stability. Notably, the as-developed magnetic 3D DNA nanomachine not only enabled the detection system to have a low background but also coupled with liposome nanocarriers to synergistically amplify the current signal. Consequently, by ingeniously combining the low background and multiple signal-amplification strategies in homogeneous electrochemical biosensing, highly sensitive detection of exosomal miRNA was successfully achieved. More significantly, with good anti-interference ability, the as-proposed method could effectively discriminate plasma samples from cancer patients and healthy subjects, thus showing a high potential for application in the nondestructive early clinical diagnosis of disease.

Molecularly Imprinted Wearable Sensor with Paper Microfluidics for Real-Time Sweat Biomarker Analysis.

The urgent need for real-time and noninvasive monitoring of health-associated biochemical parameters has motivated the development of wearable sweat sensors. Existing electrochemical sensors show promise in real-time analysis of various chemical biomarkers. These sensors often rely on labels and redox probes to generate and amplify the signals for the detection and quantification of analytes with limited sensitivity. In this study, we introduce a molecularly imprinted polymer (MIP)-based biochemical sensor to quantify a molecular biomarker in sweat using electrochemical impedance spectroscopy, which eliminates the need for labels or redox probes. The molecularly imprinted biosensor can achieve sensitive and specific detection of cortisol at concentrations as low as 1 pM, 1000-fold lower than previously reported MIP cortisol sensors. We integrated multimodal electrochemical sensors with an iontophoresis sweat extraction module and paper microfluidics for real-time sweat analysis. Several parameters can be simultaneously quantified, including sweat volume, secretion rate, sodium ion, and cortisol concentration. Paper microfluidic modules not only quantify sweat volume and secretion rate but also facilitate continuous sweat analysis without user intervention. While we focus on cortisol sensing as a proof-of-concept, the molecularly imprinted wearable sensors can be extended to real-time detection of other biochemicals, such as protein biomarkers and therapeutic drugs.

Efficient and precise delivery of microRNA by photoacoustic force generated from semiconducting polymer-based nanocarriers.

One major challenge in miRNA-based therapy is to explore facile delivery strategies, which can facilitate the efficient and precise accumulation of intrinsically instable microRNAs (miRNAs) at targeted tumor sites. To address this critical issue, for the first time we demonstrate that a near-infrared (NIR) pulse laser can guide efficient delivery of miRNAs mediated by a NIR-absorbing and photoacoustic active semiconducting polymer (SP) nanocarrier, which can generate photoacoustic radiation force to intravascularly overcome the endothelial barriers. Importantly, we demonstrate an ultrafast delivery of miRNA (miR-7) to tumor tissues under the irradiation of pulse laser in 20 min, showing a 5-fold boosted efficiency in comparison to the traditional passive targeting strategy. The delivered miR-7 acts as a sensitizer of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and synergizes with TRAIL-inducing compound (TIC), leading to sustained TRAIL upregulation for effective tumor suppression in mice. As such, our results indicate that the NIR-absorbing semiconducting polymer-mediated nanocarrier platform can significantly enhance the targeted delivery efficiency of therapeutic miRNAs to tumors, resulting in potent tumor growth inhibition.

Ultrastable Plasmonic Bioink for Printable Point-Of-Care Biosensors.

Point-of-care biosensors are critically important for early disease diagnosis and timely clinical intervention in resource-limited settings. The real-world application of these biosensors requires the use of stable biological reagents and cost-effective fabrication approaches. To meet these stringent requirements, we introduce a generic encapsulation strategy to realize ultrastable plasmonic bioink by encapsulating antibodies with an organosiloxane polymer through in situ polymerization. Plasmonic nanostructures serve as sensitive nanotransducers, allowing for label-free biochemical detection. The plasmonic bioink with encapsulated antibodies exhibits excellent thermal, biological, and colloidal stabilities making it compatible with printing process. As a proof-of-concept, we demonstrate the printability of the ultrastable plasmonic bioinks on different types of substrates with direct writing techniques. The organosiloxane polymer preserves the biorecognition capabilities of the biosensors under harsh conditions, including elevated temperature, exposure to chemical/biological denaturants, and ultrasonic agitation. Plasmonic biochips fabricated with the ultrastable ink exhibit superior stability compared to the biochips with unencapsulated antibodies.

Pigmented villonodular synovitis does not influence the outcome following cementless total hip arthroplasty using ceramic-on-ceramic articulation: a case-control study with middle-term follow-up.

BACKGROUND: Pigmented villonodular synovitis (PVNS) is a relatively rare, locally aggressive, and potentially recurrent synovial disease of large joints. The purpose of this study was to investigate (1) the disease recurrence rate and (2) the treatment outcomes including Harris hip scores, complications, and revision following cementless total hip arthroplasty (THA) with ceramic-on-ceramic (CoC) articulation in patients with PVNS. METHODS: Twenty-two patients (14 females and 8 males) with histologically confirmed PVNS underwent cementless THA using CoC bearings between 2000 and 2013. Three patients with less than 5-year follow-up were excluded. The mean age was 35.2 years (range, 22-58 years) with a mean follow-up of 8.6 years (range, 6.9-10.8 years). A control group was matched in a 2:1 ratio with the PVNS group for age, sex, body mass index (BMI), year of surgery, and American Society of Anesthesiologists score (ASA). Postoperative outcome variables included disease recurrence, Harris Hip Scores (HHS) at the latest follow-up, complications (dislocation, squeaking, ceramic fracture), and any-cause revision. A Kaplan-Meier implant survivorship curve with 95% confidence interval (CI) of the two groups was generated. RESULTS: No recurrence of PVNS was noted in the follow-up period. The HSS in the PVNS group was 92.6 ± 5.5, which was similar to the control group (93.4 ± 4.6, p = 0.584) at the last follow-up visit. No patients sustained dislocation, osteolysis, or any ceramic fracture within the study duration. One patient in the PVNS group had a complication of squeaking, but did not require revision. Another patient in the PVNS group underwent revision surgery due to aseptic loosening. There was no significant difference in revision rates between the two groups (p = 1.000). The implant survivorship free of any revision was 90.0% (95% CI, 73.2% to 100%) in the PVNS group and 92.5% (95% CI, 82.6% to 100%) in the control group at 10 years (p = 0.99). CONCLUSIONS: For young and active patients with end-stage PVNS of the hips, cementless THA using CoC bearing has similar functional outcome scores, a low complication rate, and similar implant survivorship compared to the control group.

Effects of a modified cold atmospheric plasma jet treatment on resin-dentin bonding.

The radio-frequency atmospheric-pressure glow discharge (RF-APGD) plasma is a novel cold atmospheric plasma (CAP) source, which has low energy characteristic. This study investigated the effect of RF-APGD plasma on the mechanical properties of dentin collagen and resin-dentin bonding. The scanning electron microscopy analysis was performed before and after a novel RF-APGD plasma and a conventional CAP treatment and a tensile test was carried out for the stiffness of dentin collagen. The microtensile resin-dentin bond strength was tested either immediately or after a 50,000-cycle thermocycling process. Dentin collagen maintained an intact structure after a 45-s RF-APGD plasma treatment, whereas even a 10-s treatment with the conventional CAP collapsed the collagen scaffold. When compared with control groups, the RF-APGD plasma treatment showed: (i) an improved stiffness of dentin collagen; (ii) a significant improvement in the bonding strength before/after artificial aging. Thus, RF-APGD plasma treatment has excellent prospects as a resin-dentin bonding protocol.