Abstract Backgound: Acute thrombotic events play a vital role in cardiovascular diseases. Our study aims to investigate an ultrasound microbubble fordual-modality imaging of thrombi. Methods: DID-DSPE-PEG-cRGD-Microbubbles wereprepared by mechanical vibration and Chemical chelation methods. In vivo fluorecence and ultrasound imaging were performed after by intravenous injection of DID-DSPE-PEG-cRGD-Microbubbles respectively. Results: This microbubbles exhibitedgood binding affinity to activated platelets with significant fluorescence and ultrasonic signals. Ultrasound and fluorescence imaging revealed that the microbubbles accumulated at the site of the thrombus in the carotid artery, and immunofluorescence showed that microbubbles could be detected in the carotid artery thrombus. Conclusion: We successfully synthesized novel microbubble cRGD-MBs, which indicateexcellent potential for immediate diagnosis of acute thrombus in vivo .
Atomically thin semiconductors such as transition metal dichalcogenides have recently enabled diverse devices in the emerging two-dimensional (2D) electronics. While scalable 2D electronics demand monolithic integrated circuits consisting of complementary p-type and n-type transistors, conventional p-type and n-type doping in desired regions, monolithically in the same semiconducting atomic layers, remains elusive or impractical. Here, we report on an agile, high-precision scanning laser annealing approach to realizing 2D monolithic complementary logic circuits on atomically thin MoTe2, by reliably designating p-type and n-type transport polarity in the constituent transistors via localized laser annealing and modification of their Schottky contacts. Pristine p-type field-effect transistors (FETs) transform into n-type ones upon controlled laser annealing on their source/drain gold electrodes, exhibiting a mobility of 96.5 cm2 V-1 s-1 (the highest known to date) and an On/Off ratio of 106. Elucidation and validation of such an on-demand configuration of polarity in MoTe2 FETs further enable the construction and demonstration of essential logic circuits, including both inverter and NOR gates. This dopant-free, spatially precise scanning laser annealing approach to configuring monolithic complementary logic integrated circuits may enable programmable functions in 2D semiconductors, exhibiting potential for additively manufactured, scalable 2D electronics.
Currently, the combination of smart phones and microfluidic chips is a commonly used device for point-of-care testing (POCT) detection. Enzyme linked immunosorbent assay (ELISA), as an effective method for the detection of specific proteins in diseases, has not been widely used in combination with smart phones and microfluidic chips, mainly because the detection accuracy of smart phone cameras is difficult to directly replace high-precision spectral devices. Therefore, this paper proposes a microfluidic photometric detection method based on ELISA scattering enhancement. Firstly, the scattering characteristics of IMB were mined and the optimum absorbance error compensation parameters were analyzed. Secondly, the absorbance error compensation model based on scattering enhancement characteristics is established to improve the image acquisition accuracy of smart phones. Finally, a microfluidic photometric detection chip was developed and a detection platform was established to design POCT detection App for smart phones. The optimal compensation parameters of IMB were obtained based on simulated samples, and the linearity of absorbance and concentration increased by 22.6% after compensation. In the IL-6 sample experiment, the detection results of the platform in this paper had a good linear correlation with IL-6 sample concentration, and the linear correlation coefficient was above 0.95459. At the same time, the detection limit and accuracy meet the detection requirements. Therefore, with the participation of smart phones and microfluidic chips, traditional ELISA solves problems such as difficult portability and complex operation in daily detection, laying a foundation for the promotion and application of ELISA based POCT platform in the future.
Abstract In gene therapy, intravenous injection of viral vectors reigns as the primary administration route. These vectors include adeno‐associated viruses, adenoviruses, herpes viruses, rhabdoviruses and others. However, these naturally occurring viruses lack inherent tissue or organ tropism for tailored disease treatment. To address this, we devised an optimized process involving directed viral capsid evolution, organ‐specific humanized mouse models and in vitro‐in vivo virus screening. Our approach allows for the rapid generation specifically modified adeno‐associated virus variants, surpassing the time required for natural evolution, which spans millions of years. Notably, these variants exhibit robust targeting of the liver, favouring chimeric human liver cells over murine hepatocytes. Furthermore, certain variants achieve augmented targeting with reduced off‐target organ infection, thereby mitigating dosage requirements and enhancing safety in gene therapy.
Grin2d is an ionotropic NMDA receptor, a subunit of glutamate-dependent, and a facilitator of cellular calcium influx in neuronal tissue. In this study, we found that Grin2d expression was higher in esophageal cancer than in normal mucosa at both the mRNA and protein level using RT-PCR, bioinformatics analysis, and western blotting (p<0.05). Grin2d mRNA expression was positively correlated with old age, white race, heavy weight, distal location, adenocarcinoma, cancer with Barrett's lesion, or high-grade columnar dysplasia (p<0.05). The differential genes associated with Grin2d mRNA were involved in fat digestion and absorption, cholesterol metabolism, lipid transfer, lipoproteins, synaptic membranes, and ABC transporters (p<0.05). The Grin2d-related genes were classified into the following categories: metabolism of glycerolipids, galactose, and O-glycan, cell adhesion binding, actin binding, cadherin binding, the Hippo signaling pathway, cell-cell junctions, desmosomes, DNA-transcription activator binding, and skin development and differentiation (p<0.05). Grin2d immunoreactivity was positively correlated with distal metastasis and unfavorable overall survival in esophageal cancer (p<0.05). Grin2d overexpression promoted proliferation, migration, and invasion in esophageal cancer cells but blocked apoptosis (p<0.05) and increased the expression of PI3K, Akt and p-mTOR. Grin2d knockout caused the opposite effects. These findings indicated that upregulated Grin2d expression played an important role in esophageal carcinogenesis via the PI3K/Akt/mTOR pathway and might be a biological marker for aggressive tumor behavior and poor prognosis. Its silencing might represent a targeted therapy approach against esophageal cancer.
In this paper, the pH-sensitive targeting functional material NGR-poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (NGR-PEtOz-CHMC, NPC) modified quercetin (QUE) liposomes (NPC-QUE-L) was constructed. The structure of NPC was confirmed by infrared spectroscopy (IR) and nuclear magnetic resonance hydrogen spectrum (1H-NMR). Pharmacokinetic results showed that the accumulation of QUE in plasma of the NPC-QUE-L group was 1.28 times and 2.43 times that of the QUE Solution and QUE-L groups, respectively. The release amount of NPC-QUE-L in an acidic environment was significantly higher than in physiological pH value. The order of the tumor cell inhibition rate in different pH environments was NPC-QUE-L > PC-QUE-L > QUE-L. In addition, the cellular uptake of NPC-modified liposomes was higher than that of PC-modified and unmodified liposomes, indicating that NPC had good pH-sensitivity and targeting. In the triple-negative breast cancer (TNBC) model, the relative tumor proliferation rate of NPC-QUE-L is about 73%, which is better than that of the QUE solution group. Western blot results show that NPC-QUE-L can effectively reduce the expression of α-smooth actin and transforming growth factor-β1 in tumor tissues, and improve the degree of tumor fibrosis. In this study, NPC could endow QUE liposomes with good stability, pH-sensitivity, and targeting, which provides a reference for improving the solubility and targeting of poorly soluble natural drug components.
Sperm quality assessment is the main method to predict the reproductive ability of livestock. The detection of sperm quality of livestock is of great significance to the application of artificial insemination and in vitro fertilization. In order to comprehensively evaluate sperm quality and improve the real-time and portability of sperm quality detection, a portable microscopic imaging system based on microfluidic chip is developed in this paper. The system can realize the comprehensive evaluation of sperm quality by detecting sperm vitality and survival rate. On the hardware side, a microfluidic chip is designed, which can automatically mix samples. A set of optical system with a magnification of 400 times was developed for microscopic observation of sperm. In the aspect of software, aiming at the comprehensive evaluation of sperm quality based on OpenCV, a set of algorithms for identifying sperm motility and survival rate is proposed. The accuracy of the system in detecting sperm survival rate is 94.0%, and the error rate is 0.6%. The evaluation results of sperm motility are consistent with those of computer-aided sperm analysis (CASA). The system's identification time is 9 s. Therefore, the system is absolutely suitable for sperm quality detection.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
