Evidence of deviant parasympathetic response to social exclusion in women with borderline personality disorder.

Stressful social situations like social exclusion are particularly challenging for patients with borderline personality disorder (BPD) and often lead to dysfunctional reactive behaviour of aggression and withdrawal. The autonomous signature of these core symptoms of BPD remains poorly understood. The present study investigated the parasympathetic response to social exclusion in women with BPD (n = 62) and healthy controls (HC; n = 87). In a between-subjects design, participants experienced objective social exclusion or overinclusion in the Cyberball task, a virtual ball-tossing game. Need threat scores served as individual measures of perceived exclusion and the resulting frustration of cognitive-emotional needs. Five-minute measurements of high-frequency heart rate variability (HF-HRV) at three time points (before, during, after Cyberball) indicated parasympathetic tone and regulation. We observed a trend towards lowered baseline HF-HRV in BPD vs. HC in line with previous findings. Interestingly, the parasympathetic response of patients with BPD to objective and perceived social exclusion fundamentally differed from HC: higher exclusion was associated with increased parasympathetic activation in HC, while this autonomic response was reversed and blunted in BPD. Our findings suggest that during social stress, the parasympathetic nervous system fails to display an adaptive regulation in patients with BPD, but not HC. Understanding the autonomous signature of the stress response in BPD allows the formulation of clinically relevant and biologically plausible interventions to counteract parasympathetic dysregulation in this clinical group.

CO2 Stress-Driven Room Temperature Ferromagnetism of Ultrathin 2D Gallium Oxide.

Spintronic devices work by manipulating the spin of electrons other than charge transfer, which is of revolutionary significance and can largely reduce energy consumption in the future. Herein, ultrathin two-dimensional (2D) non-van der Waals (non-vdW) γ-Ga2O3 with room temperature ferromagnetism is successfully obtained by using supercritical CO2 (SC CO2). The stress effect of SC CO2 under different pressures selectively modulates the orientation and strength of covalent bonds, leading to the change of atomic structure including lattice expansion, introduction of O vacancy, and transition of Ga-O coordination (GaO4 and GaO6). Magnetic measurements show that pristine γ-Ga2O3 is nonferromagnetic, whereas the SC CO2 treated γ-Ga2O3 exhibits obvious ferromagnetic behavior with an optimal magnetization of 0.025 emu g-1 and a Curie temperature of 300 K.

A Review of Silver Wire Bonding Techniques.

The replacement of gold bonding wire with silver bonding wire can significantly reduce the cost of wire bonding. This paper provides a comprehensive overview of silver wire bonding technology. Firstly, it introduces various types of silver-based bonding wire currently being studied by researchers, including pure silver wire, alloy silver wire, and coated silver wire, and describes their respective characteristics and development statuses. Secondly, the development of silver-based bonding wire in manufacturing and bonding processes is analyzed, including common silver wire manufacturing processes and their impact on silver wire performance, as well as the impact of bonding parameters on silver wire bonding quality and reliability. Subsequently, the reliability of silver wire bonding is discussed, with a focus on analyzing the effects of corrosion, electromigration, and intermetallic compounds on bonding reliability, including the causes and forms of chlorination and sulfurization, the mechanism and path of electromigration, the formation and evolution of intermetallic compounds, and evaluating their impact on bonding strength and reliability. Finally, the development status of silver wire bonding technology is summarized and future research directions for silver wire are proposed.

Safety and efficacy of human ESC-derived corneal endothelial cells for corneal endothelial dysfunction.

BACKGROUND: Research on human pluripotent stem cells (hPSCs) has shown tremendous progress in cell-based regenerative medicine. Corneal endothelial dysfunction is associated with the loss and degeneration of corneal endothelial cells (CECs), rendering cell replacement a promising therapeutic strategy. However, comprehensive preclinical assessments of hPSC-derived CECs for this cell therapy remain a challenge. RESULTS: Here we defined an adapted differentiation protocol to generate induced corneal endothelial cells (iCECs) consistently and efficiently from clinical-grade human embryonic stem cells (hESCs) with xeno-free medium and manufactured cryopreserved iCECs. Cells express high levels of typical CECs markers and exhibit transendothelial potential properties in vitro typical of iCECs. After rigorous quality control measures, cells meeting all release criteria were available for in vivo studies. We found that there was no overgrowth or tumorigenicity of grafts in immunodeficient mice. After grafting into rabbit models, the surviving iCECs ameliorated edema and recovered corneal opacity. CONCLUSIONS: Our work provides an efficient approach for generating iCECs and demonstrates the safety and efficacy of iCECs in disease modeling. Therefore, clinical-grade iCECs are a reliable source for future clinical treatment of corneal endothelial dysfunction.

Effects of Process Parameters on Bond Properties of Ag-2.35Au-0.7Pd-0.2Pt-0.1Cu Alloy Wire.

Bond properties were performed on Ag-2.35Au-0.7Pd-0.2Pt-0.1Cu alloy wire with a diameter of 25 µm under different process parameters. The effects of electrical flaming off (EFO) current and EFO time on the deformability of the free air ball (FAB) were investigated using scanning electron microscopy (SEM), as well as the effects of ultrasonic power and bonding force on the bond characteristic. The experimental results show that FAB grows from a preheated tip to a small ball, a regular ball, and finally to a golf ball with increasing either the EFO current or the EFO time, and the FAB presents an optimal shape at 25 mA and 650 µs. Moreover, a nonlinear relationship between FAB diameter and EFO time is obtained at an EFO current of 25 mA, which could be expressed by a cubic equation. Further, at a constant bonding force, as the ultrasonic power increased, the mashed ball diameter grew larger and larger, the capillary hole imprint became more and more obvious, and the tail width also increased, and vice versa. The optimal ultrasonic power and bonding force are 70 mW and 45 gf for ball bonding and 90 mW and 75 gf for wedge bonding, respectively. Finally, for all the bonded wire samples prepared under optimal process parameters, no ball and wedge bond lifts happened after the destructive pull test, and full intermetallic compound coverage with perfect morphology occurred on the bond pad after the ball shear test, which meant that the bonded wire samples had high bond strength and hence improved the reliability of microelectronic products. It provided technical support for the reliability research of Pt-containing Ag-based bonding alloy wires.

Copper Wire Bonding: A Review.

This paper provides a comprehensive review on copper (Cu) wire bonding. Firstly, it introduces the common types of Cu wire available in the market, including bare Cu wire, coated Cu wire, insulated Cu wire, and alloyed Cu wire. For each type, their characteristics and application areas are discussed. Additionally, we provide detailed insights into the impact of Free Air Ball (FAB) morphology on bonding reliability, including its effect on bond strength and formation mechanisms. Next, the reliability of Cu wire bonding is analyzed, with a focus on the impact of intermetallic compounds and corrosion on bonding reliability. Specifically, the formation, growth, and stability of intermetallic compounds at bonding interfaces are discussed, and their effects on bonding strength and reliability are evaluated. The detrimental mechanisms of corrosion on Cu wire bonding and corrosion inhibition methods are also analyzed. Subsequently, the applications of simulation in Cu wire bonding are presented, including finite element analysis and molecular dynamics simulations, which provide important tools for a deeper understanding of the bonding process and failure mechanisms. Finally, the current development status of Cu wire bonding is summarized, and future research directions are discussed.

High-Strength Cell Sheets and Vigorous Hydrogels from Mesenchymal Stem Cells Derived from Human Embryonic Stem Cells.

Natural cell derivates, including cell sheets (CSs) and matrix gels, have opened new opportunities to probe questions in tissue engineering and regenerative medicine. However, the potential of CSs and hydrogels generated by current protocols is still limited by the challenges of heterogeneity and weak mechanical properties. Here, we developed a 21 day long-term serum-free culture system for human embryonic stem cell (hESC)-derived immunity-and-matrix-regulatory cells (IMRCs). The CSs formed with IMRCs (IMRC-CSs) have a much greater secretion capacity for the extracellular matrix (ECM) and stronger mechanical properties than umbilical cord-derived MSCs, with a ten thousand-fold increase in elastin, a higher elastic modulus of 1500 kPa, a thicker structure of 20.59 µm, and a higher fiber count per square millimeter. The IMRC-CSs could promote corneal chemical injury repair and could be turned into injectable temperature-sensitive hydrogels for uterine adhesion repair via a decellularization process. In summary, we have established a high-strength CS platform using human pluripotent stem cells for the first time, providing a facile and scalable engineering approach for regenerative medicine.

A scalable culture system incorporating microcarrier for specialised mesenchymal stem cells from human embryonic stem cells.

Mesenchymal stromal cells (MSCs) derived from human embryonic stem cells (hESCs) are a desirable cell source for cell therapy owing to their capacity to be produced stably and homogeneously in large quantities. However, a scalable culture system for hPSC-derived MSCs is urgently needed to meet the cell quantity and quality requirements of practical clinical applications. In this study, we developed a new microcarrier with hyaluronic acid (HA) as the core material, which allowed scalable serum-free suspension culture of hESC-derived MSCs (IMRCs). We used optimal microcarriers with a coating collagen concentration of 100 â€‹µg/mL or concave-structured surface (cHAMCs) for IMRC amplification in a stirred bioreactor, expanding IMRCs within six days with the highest yield of over one million cells per milliliter. In addition, the harvested cells exhibited high viability, immunomodulatory and regenerative therapeutic promise comparable to monolayer cultured MSCs while showing more increased secretion of extracellular matrix (ECM), particularly collagen-related proteins. In summary, we have established a scalable culture system for hESC-MSCs, providing novel approaches for future cell therapies.

Human embryonic stem cell-derived immunity-and-matrix regulatory cells promote intrahepatic cell renewal to rescue acute liver failure.

Acute liver failure (ALF) is a clinical syndrome characterized by the accelerated development of hepatocyte necrosis and significant mortality. Given that liver transplantation is now the only curative treatment available for ALF, there is an urgent need to explore innovative therapies. Mesenchymal stem cells (MSCs) have been applied in preclinical studies for ALF. It had been demonstrated that human embryonic stem cell-derived immunity-and-matrix regulatory cells (IMRCs) met the properties of MSCs and had been employed in a wide range of conditions. In this study, we conducted a preclinical evaluation of IMRCs in the treatment of ALF and investigated the mechanism involved. ALF was induced in C57BL/6 mice via intraperitoneal administration of 50% CCl4 (6 mL/kg) mixed with corn oil, followed by intravenous injection of IMRCs (3 × 106 cells/each). IMRCs improved histopathological changes in the liver and reduced alanine transaminase (ALT) or aspartate transaminase (AST) levels in serum. IMRCs also promoted cell renewal in the liver and protected it from CCl4 damage. Furthermore, our data indicated that IMRCs protected against CCl4-induced ALF by regulating the IGFBP2-mTOR-PTEN signaling pathway, which is associated with the repopulation of intrahepatic cells. Overall, IMRCs offered protection against CCl4-induced ALF and were capable of preventing apoptosis and necrosis in hepatocytes, which provided a new perspective for treating and improving the prognosis of ALF.

Research Progress on Bonding Wire for Microelectronic Packaging.

Wire bonding is still the most popular chip interconnect technology in microelectronic packaging and will not be replaced by other interconnect methods for a long time in the future. Au bonding wire has been a mainstream semiconductor packaging material for many decades due to its unique chemical stability, reliable manufacturing, and operation properties. However, the drastic increasing price of Au bonding wire has motivated the industry to search for alternate bonding materials for use in microelectronic packaging such as Cu and Ag bonding wires. The main benefits of using Cu bonding wire over Au bonding wire are lower material cost, higher electrical and thermal conductivity that enables smaller diameter Cu bonding wire to carry identical current as an Au bonding wire without overheating, and lower reaction rates between Cu and Al that serve to improve the reliability performance in long periods of high temperature storage conditions. However, the high hardness, easy oxidation, and complex bonding process of Cu bonding wire make it not the best alternative for Au bonding wire. Therefore, Ag bonding wire as a new alternative with potential application comes to the packaging market; it has higher thermal conductivity and lower electric resistivity in comparison with Cu bonding wire, which makes it a good candidate for power electronics, and higher elastic modulus and hardness than Au bonding wire, but lower than Cu bonding wire, which makes it easier to bond. This paper begins with a brief introduction about the developing history of bonding wires. Next, manufacturability and reliability of Au, Cu, and Ag bonding wires are introduced. Furthermore, general comparisons on basic performance and applications between the three types of bonding wires are discussed. In the end, developing trends of bonding wire are provided. Hopefully, this review can be regarded as a useful complement to other reviews on wire bonding technology and applications.

Oxytocin vs. placebo effects on intrusive memory consolidation using a trauma film paradigm: a randomized, controlled experimental study in healthy women.

Oxytocin administration during a trauma analogue has been shown to increase intrusive memories, which are a core symptom of post-traumatic stress disorder (PTSD). However, it is unknown whether oxytocin influences the acquisition or the consolidation of the trauma. The current study investigates the effect of the activation of the oxytocin system during the consolidation of an analogue trauma on the formation of intrusive memories over four consecutive days and whether this effect is influenced by individual neurobiological, genetic, or psychological factors. We conducted a randomized double-blind placebo-controlled study in 217 healthy women. They received either a single dose of intranasal oxytocin (24 IU) or placebo after exposure to a trauma film paradigm, which reliably induces intrusive memories. We used a general random forest to examine a potential heterogeneous treatment effect of oxytocin on the consolidation of intrusive memories. Furthermore, we used a poisson regression to examine whether salivary alpha amylase activity (sAA) as a marker of noradrenergic activity and cortisol response to the film, polygenic risk score (PRS) for psychiatric disorders, and psychological factors influence the number of intrusive memories. We found no significant effect of oxytocin on the formation of intrusive memories (F(2, 543.16) = 0.75, p = 0.51, ηp2 = 0.00) and identified no heterogeneous treatment effect. We replicated previous associations of the PRS for PTSD, sAA and the cortisol response on intrusive memories. We further found a positive association between high trait anxiety and intrusive memories, and a negative association between the emotion regulation strategy reappraisal and intrusive memories. Data of the present study suggest that the consolidation of intrusive memories in women is modulated by genetic, neurobiological and psychological factors, but is not influenced by oxytocin. Trial registration: NCT03875391.

Impact of social exclusion on empathy in women with borderline personality disorder.

Unstable interpersonal relationships and fear of abandonment are core symptoms of borderline personality disorder (BPD) that often intensify during stress. Psychosocial stress, which includes components of social exclusion and increases cortisol secretion, enhances emotional empathy in healthy individuals. Women with BPD, on the contrary, react with reduced emotional empathy. The aim of the present study was to investigate the effects of perceived social exclusion without accompanying cortisol increase on empathy in women with BPD and healthy women. To induce social exclusion, we randomized 98 women with BPD and 98 healthy women to either an exclusion or an overinclusion (control) condition of Cyberball, a virtual ball game. Subsequently, participants underwent the Multifaceted Empathy Test (MET), which assesses cognitive and emotional empathy. There was no increase in cortisol release after Cyberball. Cognitive empathy did not differ between groups or conditions. Women with BPD reported lower emotional empathy for positive emotions (group by valence interaction), but not for negative emotions. Exploratory analyses suggested that this effect might be more pronounced after social exclusion. Our results confirm previous findings that cognitive empathy does not differ between women with BPD and healthy women and extend this evidence to social exclusion. Emotional empathy in women with BPD seems to be more sensitive to the effects of stress or ambiguous social situations. Specifically, emotional empathy seems to be reduced for positive emotions, and might further decline after social exclusion. Empathic reactions to emotional stimuli of different valences and to specific emotions should be further investigated.

Effects of multimodal analgesia of flurbiprofen axetil, nalbuphine and patient controlled intravenous analgesia on inflammatory factor levels and stress response in patients after laparoscopic radical gynecological malignancy surgery.

To evaluate the efficacy of multimodal analgesia of flurbiprofen axetil, nalbuphine hydrochloride and patient controlled intravenous analgesia (PCIA) on inflammatory factor levels and stress response in patients after laparoscopic radical gynecological malignancy surgery. The data of 100 patients admitted to our hospital from May 2019 to May 2020 for laparoscopic radical gynecological malignancy surgery were retrospectively analyzed and they were assigned (1:1) to either an experimental group or a control group according to the alphabetical order of their initials. The experimental group was given preemptive analgesia with flurbiprofen axetil, postoperative analgesia with nalbuphine hydrochloride, and PCIA and the control group was given conventional analgesic measures. The pain scores at 1h, 6h, 12h, 24h and 48h postoperatively in the experimental group were remarkably lower than those in the control group (P<0.001). The experimental group showed significantly lower inflammatory factor levels, pain mediator levels and stress response indexes in the morning before surgery, 1d, and 2d after surgery than the control group (P<0.001). The multimodal analgesia of flurbiprofen axetil, nalbuphine hydrochloride and PCIA can effectively alleviate the stress response and inflammatory response in patients after radical gynecologic malignancy surgery and the patients' pain perception is reduced with a high safety profile.

[Clinical effects of matrix acupuncture on cervical spondylotic radiculopathy with nuchal ligament calcification].

OBJECTIVE: To observe the effects of matrix acupuncture on the neck disability index (NDI) score, clinical efficacy, and the calcification size of the nuchal ligament in patients of cervical spondylotic radiculopathy with nuchal ligament calcification. METHODS: A total of 120 cases were randomly divided into a matrix acupuncture group and a routine acupuncture group, with 60 cases in each group. In the matrix acupuncture group, Ashi-point, bilateral Tianzhu (BL10), bilateral Fengchi (GB20), bilateral Dazhu (BL11), bilateral Jianzhongshu (SI15), and Jianjing (GB21), Tianzong (SI11), Quchi (LI11), Shousanli (LI10), Waiguan (TE5), and Hegu (LI4) at the affected side were selected. In the routine acupuncture group, C3-C7 Jiaji points at the neck and Jianjing (GB21), Tianzong (SI11), Quchi (LI11), Shousanli (LI10), Waiguan (TE5), Hegu (LI4), and Ashi-point at the affected side were selected. The patients in the two groups were treated 30 min once, six days a week, for a total of four weeks. The NDI scores, clinical efficacies, and calcification sizes of nuchal ligament were compared between the two groups every wee-kend. RESULTS: After four weeks of treatment, the NDI scores and calcification volumes of nuchal ligament decreased in both groups (P<0.05). Compared with the routine acupuncture group, the matrix acupuncture group showed decreased NDI scores and reduced calcification volumes of nuchal ligament at the 1st, 2nd, 3rd, and 4th weeks of treatment (P<0.05). The cure and marked effective rate in the matrix acupuncture group at the 2nd, 3rd, and 4th weeks of treatment were superior to those of the routine acupuncture group (P<0.05). CONCLUSION: The matrix acupuncture group and the routine acupuncture group are effective in reducing the NDI score and calcification size of nuchal ligament in patients of cervical spondylotic radiculopathy with nuchal ligament calcification. However, matrix acupuncture has obvious advantages over routine acupuncture.

Motor signature of autism spectrum disorder in adults without intellectual impairment.

Motor signs such as dyspraxia and abnormal gait are characteristic features of autism spectrum disorder (ASD). However, motor behavior in adults with ASD has scarcely been quantitatively characterized. In this pilot study, we aim to quantitatively examine motor signature of adults with ASD without intellectual impairment using marker-less visual-perceptive motion capture. 82 individuals (37 ASD and 45 healthy controls, HC) with an IQ > 85 and aged 18 to 65 years performed nine movement tasks and were filmed by a 3D-infrared camera. Anatomical models were quantified via custom-made software and resulting kinematic parameters were compared between individuals with ASD and HCs. Furthermore, the association between specific motor behaviour and severity of autistic symptoms (Autism Diagnostic Observation Schedule 2, Autism Spectrum Quotient) was explored. Adults with ASD showed a greater mediolateral deviation while walking, greater sway during normal, tandem and single leg stance, a reduced walking speed and cadence, a greater arrhythmicity during jumping jack tasks and an impaired manual dexterity during finger tapping tasks (p < 0.05 and |D|> 0.48) compared to HC. Furthermore, in the ASD group, some of these parameters correlated moderately to severity of ASD symptoms. Adults with ASD seem to display a specific motor signature in this disorder affecting movement timing and aspects of balance. The data appear to reinforce knowledge about motor signs reported in children and adolescents with ASD. Also, quantitative motor assessment via visual-perceptive computing may be a feasible instrument to detect subtle motor signs in ASD and perhaps suitable in the diagnosis of ASD in the future.

Prediction of post-transplant graft survival by different definitions of early allograft dysfunction.

BACKGROUND: The efficacy of early allograft dysfunction (EAD) definitions in predicting post-transplant graft survival in a Chinese population is still unclear. METHODS: A total of 607 orthotopic liver transplants (OLT) have been included in the current study. Model accuracy was evaluated using receiver operating characteristic (ROC) analysis. Risk factors for EAD was evaluated using univariable analysis and multivariable logistic regression model. RESULTS: The 3-, 6-, and 12-month patient/graft survival were 91.6%/91.4%, 91.1%/90%, and 87.5%/87.3%, respectively. MELDPOD5 had a superior discrimination of 3-month graft survival (C statistic, 0.83), compared with MEAF (C statistic, 0.77) and Olthoff criteria (C statistic, 0.72). Multivariate analysis of risk factors for EAD defined by MELDPOD5, showed that donor body mass index (P=0.001), donor risk index (P=0.006), intraoperative use of packed red blood cells (P=0.001), hypertension of recipient (P=0.004), and preoperative total bilirubin (P<0.001) were independent risk factors. CONCLUSIONS: The results suggest that MLEDPOD5 is a better criterion of EAD for the Chinese population, which might serve as a surrogate end-point for graft survival in clinical study.

Infusion of hESC derived Immunity-and-matrix regulatory cells improves cognitive ability in early-stage AD mice.

OBJECTIVES: In this study, we administered immunity-and-matrix regulatory cells (IMRCs) via tail vein (IV) and intracerebroventricular (ICV) injection to 3-month-old 5×FAD transgenic mice to assess the effects of IMRC transplantation on the behaviour and pathology of early-stage Alzheimer's disease (AD). MATERIALS AND METHODS: Clinical-grade human embryonic stem cell (hESC)-derived IMRCs were produced under good manufacturing practice (GMP) conditions. Three-month-old 5×FAD mice were administered IMRCs via IV and ICV injection. After 3 months, the mice were subjected to behavioural tests and electrophysiological analysis to evaluate their cognitive function, memory ability and synaptic plasticity. The effect of IMRCs on amyloid-beta (Aß)-related pathology was detected by thioflavin-S staining and Western blot. Quantitative real-time PCR, ELISA and immunostaining were used to confirm that IMRCs inhibit neuroinflammation. RNA-seq analysis was performed to measure changes in gene expression and perform a pathway analysis in response to IMRC treatment. RESULTS: IMRC administration via tail vein injection significantly ameliorated cognitive deficits in early-stage AD (5×FAD) mice. However, no significant change was observed in the characteristic pathology of AD in the ICV group. Plaque analysis revealed that IMRCs did not influence either plaque deposition or BACE1 expression. In addition, IMRCs inhibited inflammatory responses and reduced microglial activation in vivo. CONCLUSIONS: We have shown that peripheral administration of IMRCs can ameliorate AD pathology and associated cognitive deficits.

Effect of multimodal analgesia on gynecological cancer patients after radical resection.

OBJECTIVE: This research was designed to probe into the effect of multimodal analgesia on gynecological cancer patients after radical resection. METHODS: Ninety-eight cervical cancer patients undergoing laparoscopic radical resection in our hospital were included. Thereinto, 47 in the research group (RG) were given multimodal analgesia, and 51 in the control group (CG) were given conventional postoperative analgesia. The time of operation, anesthesia recovery room observation and extubation, postoperative NRS pain score, and the clinical manifestations of both groups were observed. The activity within three days after operation, the incidence of postoperative complications, hospitalization time and quality of life of both groups were compared. RESULTS: The operation time of the RG was higher than that of the CG (P < 0.05), and the time of observation and extubation in the anesthesia room were lower than those in the CG (P < 0.05); the NRS pain score was lower than that of the CG (P < 0.05); the first time to get out of bed, and time of exhaust and diet were shorter than those of the CG (P < 0.05); the activity was better than that of the CG within three days after operation (P < 0.05); the incidence of complications was markedly lower than that in the CG (P < 0.05); the hospitalization time was shorter than that of the CG (P < 0.05); the postoperative quality of life was shorter than that in the CG (P < 0.05). CONCLUSION: Multimodal analgesia is safe and effective for patients after laparoscopic radical resection of gynecological malignancies, which can speed up the recovery of diseases and improve the quality of life. Thus, it is worthy of clinical application.

Precise Capture and Direct Quantification of Tumor Exosomes via a Highly Efficient Dual-Aptamer Recognition-Assisted Ratiometric Immobilization-Free Electrochemical Strategy.

Tumor exosomes are promising biomarkers for early cancer diagnosis in a noninvasive manner. However, precise capture and direct analysis of tumor-specific exosomes in complex biological samples are still challenging. Herein, we present a highly efficient dual-aptamer recognition system for precisely isolating and quantifying tumor exosomes from the complex biological environment based on hyperbranched DNA superstructure-facilitated signal amplification and ratiometric dual-signal strategies. When tumor exosomes were captured by the dual-aptamer recognition system, the cholesterol-modified DNA probe was anchored on the surface of the exosomes, activating DNA tetrahedron-based hyperbranched hybridization chain reaction to generate a sandwich complex. Then, the sandwich complex could bind a large number of Ru(NH3)63+ (Ru(III)), leading to a small amount of unbound Ru(III) left in the supernatant after magnetic separation. Hence, the redox reaction between Ru(II) and [Fe(CN)6]3- (Fe(III)) was significantly prevented, causing an obviously enhanced IFe(III)/IRu(III) value. Consequently, highly sensitive detection of tumor exosomes was achieved. The developed approach successfully realized direct isolation and analysis of tumor exosomes in complex sample media and human serum samples as well. More significantly, this ratiometric dual-signal mode and immobilization-free strategy effectively circumvented the systematic errors caused by external factors and the tedious probe immobilization processes, thus displaying the excellent performances of high reliability, improved accuracy, and easy manipulation. Overall, this approach is expected to offer novel ways for nondestructive early cancer diagnosis.

A competitive coordination-based immobilization-free electrochemical biosensor for highly sensitive detection of arsenic(v) using a CeO2-DNA nanoprobe.

We developed a competitive coordination-based immobilization-free electrochemical biosensor for highly sensitive and selective detection of arsenic(v) using a CeO2-DNA nanoprobe, which effectively circumvented complicated modification procedures and successfully achieved arsenic(v) determination in natural water samples.