Tunneling Nanotubes Mediate KRas Transport: Inducing Tumor Heterogeneity and Altering Cellular Membrane Mechanical Properties.

Mutation in oncogene KRas plays a crucial role in the occurrence and progression of numerous malignant tumors. Malignancy involves changes in cell mechanics for extensive cellular deformation during metastatic dissemination. We hypothesize that oncogene KRas mutations are intrinsic to alterations in cellular mechanics that promote malignant tumor generation and progression. Here, we demonstrate the use of optical tweezers coupled with a confocal fluorescence imaging system and gene interference technique to reveal that the mutant KRas protein can be transported between homogeneous and heterogeneous tumor cells by tunneling nanotubes (TNTs), resulting in a significant reduction of membrane tension and acceleration of membrane phospholipid flow in the recipient cells. Simultaneously, the changes in membrane mechanical properties of the tumor cells also enhance the metastatic and invasive ability of the tumors, which further contribute to the deterioration of the tumors. This finding helps to clarify the association between oncogene mutations and changes in the mechanical properties of tumor cells, which provides a theoretical basis for the development of cancer treatment strategies. STATEMENT OF SIGNIFICANCE: Here, we present a laser confocal fluorescence system integrated with optical tweezers to observe the transfer of mutant KRasG12D protein from mutant cells to wild-type cells through TNTs. Malignancy involves changes in cell mechanics for extensive cellular deformation during metastatic dissemination. Our results demonstrate a significant decrease in membrane tension and an increase in membrane phospholipid flow in recipient cells. These alterations in mechanical properties augment the migration and invasive capabilities of tumor cells, contributing to tumor malignancy. Our findings propose that cellular mechanical properties could serve as new markers for tumor development, and targeting membrane tension may hold potential as a therapeutic strategy.

Correction: A label-free and immobilization-free approach for constructing photoelectrochemical nucleic acid sensors utilizing DNA-silver nanoparticle affinity interactions.

Correction for 'A label-free and immobilization-free approach for constructing photoelectrochemical nucleic acid sensors utilizing DNA-silver nanoparticle affinity interactions' by Jing Yi et al., Analyst, 2024, https://doi.org/10.1039/D4AN00098F.

A label-free and immobilization-free approach for constructing photoelectrochemical nucleic acid sensors utilizing DNA-silver nanoparticle affinity interactions.

Efficient and affordable nucleic acid detection methods play a pivotal role in various applications. Herein, we developed an immobilization-free and label-free strategy to construct a photoelectrochemical nucleic acid biosensing platform based on interactions between silver nanoparticles and DNA. First, CRISPR-Cas12a exhibited a trans-cleavage effect on adenine nucleotide sequences upon recognizing the target DNA. The resulting adenine nucleotide sequences of varying lengths then engaged in interactions with silver nanoparticles, leading to a solution characterized by distinct light transmittance. Subsequently, the solution was positioned between the light source and the photoelectrode, strategically impacting the photon absorption step within the photoelectrochemical process. Consequently, the detection of nucleic acid was accomplished through the analysis of the resultant photocurrent signal. The developed platform exhibits a detection limit of 0.06 nM (S/N = 3) with commendable selectivity. The innovative use of adenine nucleotide sequences as cost-effective probes interacting with silver nanoparticles eliminates the need for complex interfacial immobilization processes, significantly simplifying the fabrication of DNA sensors. The outcomes of our research present a promising pathway for advancing the development of economically feasible miniature DNA sensors.

[Clinical significance of monitoring coagulation- and fibrinolysis-related indexes during catheter-directed thrombolysis for acute lower-extremity deep venous thrombosis].

OBJECTIVE: To investigate the patterns of changes in serum levels of of D-dimer, fibrinogen (FIB) and fibrin degradation product (FDP) during catheter-directed thrombolysis (CDT) in patients with acute lower-extremity deep venous thrombosis (DVT) and explore their clinical significance. METHODS: From June, 2014 to June, 2015, 50 patients with acute lower-extremity DVT received CDT. The serum concentrations of D-dimer, FIB and FDP were measured before, during and after CDT in all the subjects, with 50 healthy subjects serving as the control group. RESULTS: Compared with the control group, the patients in DVT group showed significantly increased serum levels of D-dimer (29.17±38.67 vs 0.21 ±0.27 µg/mL), FIB (3.66±0.95 vs 3.32±0.65 g/L) and FDP (76.14±131.48 vs 1.08±0.73 µg/mL) before CDT (P<0.05). Based on the effect of CDT, the patients with DVT were divided into recanalization group (n=34) and failed recanalization group (n=16), and the patients with recanalization had significantly increased serum concentration of D-dimer and FDP (P<0.05) and decreased FIB level (P<0.05) compared with those with failed recanalization at 24 h of CDT. D-dimer, FDP, and FIB showed no significant changes in the patients with failed recanalization after the procedure (P>0.05). Correlation analysis showed that serum D-dimer (r=0.66, P<0.05) and FDP (r=0.50, P<0.05) at 24 h of the procedure were positively correlated with the outcomes of CDT. CONCLUSION: Serum levels of D-dimer, FIB and FDP are important indicators for evaluating and predicting the effectiveness of CDT in patients with acute DVT.