Profiling DNA Cargos in Single Extracellular Vesicles via Hydrogel-Based Droplet Digital Multiple Displacement Amplification.

Due to the substantial heterogeneity among extracellular vesicle (EV) subpopulations, single-EV analysis has the potential to elucidate the mechanisms behind EV biogenesis and shed light on the myriad functions, leading to the development of novel diagnostics and therapeutics. While many studies have been devoted to reveal between-EV variations in surface proteins and RNAs, DNA cargos (EV-DNA) have received little attention. Here, we report a hydrogel-based droplet digital multiple displacement amplification approach for the comprehensive analysis of EV-DNA at the single-EV level. Single EVs are dispersed in thousands of hydrogel droplets and lysed for DNA amplification and identification. The droplet microfluidics strategy empowers the assay with single-molecule sensitivity and capability for absolute quantification of DNA-containing EVs. In particular, our findings indicate that 5-40% EVs are associated with DNA, depending on the cell of origin. Large EVs exhibit a higher proportion of DNA-containing EVs and a more substantial presence of intraluminal DNA, compared to small EVs. These DNA-containing EVs carry multiple DNA fragments on average. Furthermore, both double-stranded DNA and single-stranded DNA were able to be detected at the single-EV level. Utilizing this method, the abundance, distribution, and biophysical properties of EV-DNA in various EV populations are evaluated. The DNA level within EVs provides insight into the status of the originating cells and offers valuable information on the outcomes of anticancer treatments. The utilization of single-EV analysis for EV-DNA holds significant promise for early cancer detection and treatment response monitoring.

Investigating the Molecular Rearrangement of Polar Liquid Mixtures Using Terahertz Frequency Domain Reflection Spectroscopy.

A special data processing method for the terahertz frequency domain reflection spectroscopy system has been proposed to analyze the characteristics of a polar mixed liquid. This novel and practical measurement system is characterized by a simpler optical structure and a tunable output frequency range of 0.1-1 THz. By Hilbert transform, stationary wavelet transform, and time domain zero setting method, the reflection coefficient that has been eliminated by the noise and the Fabry-Pérot effect can be obtained by the self-reference calibration method. Then, the dielectric function of the ethanol/n-hexane and propanol/n-hexane mixtures with different mixture ratios can be extracted by this method. In addition, a significant deviation can be observed between the imaginary part of the measured dielectric function and the ideal calculated value. These results indicate that during the mixing process of polar and nonpolar liquids, the hydroxyl functional groups of alcohols significantly change the molecular arrangement pattern of the mixture. The arrangement pattern will result in the formation of the new permanent dipole moment. This study lays a solid foundation for future research on the microscopic mechanism of intermolecular interaction using terahertz frequency domain reflection spectroscopy.

Countermeasures for the Development of Data Integration of the Internet Ice and Snow Tourism Industry under the Background of Artificial Intelligence.

Under the background of "Internet + Ice and Snow Tourism," the tourism industry has ushered in new development opportunities and external challenges. "Internet + tourism" breeds a new huge tourism market. This new market consists of netizens + purchasing power + purchasing desire. This paper mainly selects the integration of mobile ice and snow tourism and tourism and leisure industry as the main research subject, focusing on the in-depth study of the future development trend of the integration of ice and snow tourism and leisure industry and the mobile Internet industry. The analysis found that the tourism industry in the ice and snow area mainly has the following problems: the division of functional areas is not clear, there is a large gap between service innovation capabilities and industrial demand, and the level of industrial informatization is inconsistent with development goals and the lack of market service credit. On the basis of combining tourism Internet service platform and big data marketing experience, creatively propose to create a new development pattern of "one network, three places and one platform" for ice and snow tourism, promote the "Three New Coverage Projects" of the tourism network, and build a new cross-business cooperation mechanism of "Internet + Tourism"; rely on Internet marketing and publicity measures to enhance the development of tourism service integrity and other countermeasures; use Internet thinking to solve the problems of tourism industry development; and provide suggestions for the innovative development of the tourism industry in the ice and snow regions and the entire autonomous region. The implementation of these countermeasures predicts that the local economy will increase by at least 51.28%, so the development of the "Internet + ice and snow tourism" type industry in combination with the actual situation is not waiting.

Comprehensive investigation on metabolites of Panax quinquefolium L. in two main producing areas of China based on ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

Jilin Province and Shandong Province are two main American ginseng (AG) producing areas in China. The geographical difference existed in these two provinces. Aiming at evaluating the similarities and differences of the secondary metabolites, the comprehensive metabolite profiling of AG from Jilin Province (AGJ ) and Shandong Province (AGS ) was performed based on UPLC-QTOF-MS for the first time. In screening analysis, a total of 111 shared compounds, with ginsenosides being major components, were identified or tentatively characterized, which indicated that AGJ and AGS were all rich in phytochemicals and contained similar structural types. Untargeted metabolomics analysis indicated that there were significant differences in the contents of certain constituents in AGJ and AGS . Nineteen (12 for AGJ , 7 for AGS ) potential producing area-dependent chemical markers were discovered. Based on the contents and MS responses, ginsenoside Rg1 , Re, and pseudoginsenoside F11 could be considered as the characteristical markers of AGJ , whereas ginsenoside Rg3 and Rh2 of AGS . This comprehensive phytochemical profile study could provide valuable chemical evidence for evaluating the characteristics qualities of AG from various producing areas.

Comprehensive phytochemical profiling of American ginseng in Jilin province of China based on ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry.

American ginseng (AG), the underground part of Panax quinquefolium L., is composed of four morphological regions, including main root (MR), lateral root (LR), fibrous root (FR), and rhizome (RH). In the clinical, MR is the main medicinal region, other regions are rarely attention. Aiming at revealing the chemical composition of AG and making better use of AG, screening analysis and metabolomic analysis were both performed to profile MR, LR, FR, and RH. First, in the systematical screening analysis, a total of 134 compounds (including 122 shared components) with various structural patterns were identified and tentatively characterized. The results indicated that the phytochemicals with various structural types were rich in MR, LR, FR, and RH. Second, 6, 4, 8, and 11 chemical markers were identified from MR, LR, FR, and RH, respectively. Seven triterpene saponins (protopanaxatriol, quinquenoside R1 , ginsenoside Rc, Rk1 , Rg1 , Re, and vinaginsenoside R1 ) might be used for rapid differentiation of four morphological regions. This comprehensive profile study of metabolites illustrated the similarities and differences of phytochemicals in four morphological regions of AG. The results could be used for the quality control of AG and furnish a basis for the further development and utilization of AG sources.

New Polylactic Acid Multifunctional Ultrasound Contrast Agent Based on Graphene Oxide as the Carrier of Targeted Factor and Drug Delivery.

In recent years, the development of ultrasound contrast agents has encouraged their use as a drug system for diagnosis and therapy. In this paper, polylactic acid (PLA) composite microbubbles (FA/DOX/GO/DOX/PLA) were prepared with graphene oxide (GO) as a carrier of the targeted factor folic acid (FA) and doxorubicin (DOX) by the multiple emulsification-solvent evaporating process. Appearance, particle size, and zeta potential of PLA composite microbubbles were characterized by using a nanoparticle size analyzer and transmission electron microscopy. Breast cancer cells MCF-7 were used to evaluate the antitumor activity of PLA composite microbubbles in vitro by using the CCK-8 and acridine orange staining method. The ultrasonic imaging effect of PLA composite microbubbles was investigated in New Zealand white rabbits by the Doppler color ultrasound imaging system. With Kunming mice as the research model, the acute toxicity of PLA composite microbubbles was examined. The experimental results showed that the prepared PLA composite microbubbles presented a hollow and spherical shape with a particle size of 600 nm or so and a zeta potential of -37.5 ± 10.0 mV. They had a good effect of the enhancing imaging, and clear ultrasound imaging can be obtained. PLA composite microbubbles showed a significant proliferation inhibition effect on breast cancer cells MCF-7 in a dose-dependent manner. After PLA composite microbubbles were modified by FA, they were good for targeting FA receptors on the surface of MCF-7 cells, which increased the inhibition rate of the tumor cells. LD50 of PLA composite microbubbles was 87.529 mg·kg-1; the mice did not show the acute toxicity when the dose of composite microbubbles was lower than this value.

Enhanced ultrasound imaging and anti-tumor in vivo properties of Span-polyethylene glycol with folic acid-carbon nanotube-paclitaxel multifunctional microbubbles.

With Span and polyethylene glycol (PEG) as the membrane material, the as-prepared folate-carbon nanotube-paclitaxel (FA-CNT-PTX) complex was added to the reaction system under sound vibration cavitation and Span-PEG with FA-CNT-PTX microbubbles was obtained. The maximum tolerating dose of the obtained composite microbubbles on Kunming mice was determined by acute toxicity test. Utilizing the breast cancer tumor model in the nude mice to assess the anti-tumor activity in vivo, the inhibition effect of the composite microbubbles on tumor growth was analyzed by recording the weight and tumor volume of the nude mice. HE staining observations, the immunohistochemistry method, and TUNEL were, respectively, used to examine the inhibition effect of the composite microbubbles on breast cancer tumors in the nude mice. The ultrasound imaging effects and the changes in the peak intensities of the composite microbubbles were inspected using a Doppler color ultrasound imaging system. The experimental results showed that the maximum tolerated dose of the composite microbubbles was 3500 mg kg-1, indicating that the composite microbubbles had low toxicity and good biocompatibility. The composite microbubbles could reach the breast cancer tumor via a targeting factor, and then hindered the tumor growth by inhibiting the proliferation of tumor cells and inducing apoptosis of the tumor cells. The composite microbubbles contributed toward enhancing the ultrasound signal and improved the resolution of the ultrasound images and extended the imaging time. Also, the addition of CNTs in the composite microbubbles could enhance the ultrasound contrast. Simultaneously, the peak intensity at the tumor was significantly reduced after the treatment.

Enhancing the performance of Mg-based implant materials by introducing basal plane stacking faults.

One of the keys to allowing Mg alloys to serve as biodegradable materials is how to balance their degradation behaviours and mechanical properties in physiological environment. In this study, a novel Mg-6Ho-0.5Zn alloy (wt%) containing profuse basal plane stacking faults (SFs) is prepared. This newly-developed alloy with SFs exhibiting uniform corrosion behaviour, low corrosion rate and high mechanical properties, as compared to the classic Mg-Ho based alloys (Mg-6Ho and Mg-6Ho-1.5Zn). Furthermore, the Mg-6Ho-0.5Zn alloy shows no significant toxicity to Saos-2 cells. An original uniform corrosion mechanism is proposed by combining the special defect structure, orientation of SFs and promptly effective corrosion film. The development of the new microstructure for Mg-Ho based alloys with desirable corrosion performance has important implications in developing novel degradable Mg-based implant materials.

[Reverse second dorsal metatarsal artery island flap for repairing the soft tissue defect at toes].

OBJECTIVE: To report the application of reverse second dorsal metatarsal artery island flap for From May 2005 to September 2008, 5 cases with soft tissue repairing the soft tissue defect at toes. METHODS: defects at toes were treated with reverse second dorsal metatarsal artery island flaps. The flaps size ranged from 2 cm x 3 cm to 5 cm x 6 cm. RESULTS: All the 5 flaps survived completely. The patients could walk 1-2 months after operation. The patients were followed up for 5-7 months with good appearance, texture and sensation of toes. CONCLUSION: The reverse second dorsal metatarsal artery island flap has a reliable blood supply and good tissue texture. It is a practical method for repairing the soft tissue defect at toes.

[Repair of the soft tissue defect of the fifth finger with a reversed ulnar fasciocutaneous flap from the fifth metacarpal side].

OBJECTIVE: To introduce a method by reversed ulnar fasciocutaneous flap incised form the ulnar side of the fifth metacarpal area for repairing the soft tissue defect of the fifth finger. METHODS: From May 2001 to September 2001, ten patients with the soft tissue defects of the thenar side, dorsal side or ulnar side of the fifth finger were treated with the reversed ulnar fasciocutaneous flap incised from the fifth metacarpal area. The axial line of the flap was the line from ulnar side of the head of the fifth metacarpal bone to the pisiform level. The revolving point of the flap pedicle was 0.5-1 cm near the proximal end of the metacarpal-phalangeal joint.The area of the flap was form 5.0 cm x 3.5 cm to 1.5 cm x 1.0 cm. RESULTS: All flaps of the ten cases were alive. 5-7 months followed-up show that, after operation, the flap present sensation in 6-12 mm, with soft texture and good appearances. CONCLUSIONS: The advantages of this operative method were as follows: the reversed ulnar fasciocutaneous flap of the fifth metacarpal area have reliable blood supply, it was easily dissected and with good texture. So far this kind of flap is a good choice in repairing the soft tissue of the fifth finger.