Visualization of specific genomic loci in live cells is a prerequisite for the investigation of dynamic changes in chromatin architecture during diverse biological processes, such as cellular aging. However, current precision genomic imaging methods are hampered by the lack of fluorescent probes with high specificity and signal-to-noise contrast. We find that conventional transcription activator-like effectors (TALEs) tend to form protein aggregates, thereby compromising their performance in imaging applications. Through screening, we found that fusing thioredoxin with TALEs prevented aggregate formation, unlocking the full power of TALE-based genomic imaging. Using thioredoxin-fused TALEs (TTALEs), we achieved high-quality imaging at various genomic loci and observed aging-associated (epi) genomic alterations at telomeres and centromeres in human and mouse premature aging models. Importantly, we identified attrition of ribosomal DNA repeats as a molecular marker for human aging. Our study establishes a simple and robust imaging method for precisely monitoring chromatin dynamics in vitro and in vivo.

Objective: Poor blood flow supply is an important pathological factor that leads to the development and deterioration of diabetic foot ulcers. This study aims to investigate the acute effects of local vibration with varying intermittent durations on the plantar skin blood flow (SBF) response in diabetic and healthy subjects.Methods: Eleven diabetic patients (7 males, 4 females) and 15 healthy adults (6 males, 9 females) participated in this experiment and accepted three tests. Local continuous vibration (LCV) and two levels of local intermittent vibration (LIV1 and LIV2) were randomly applied to the middle metatarsal head of each subject's right foot in each test. The SBF was measured prior to intervention (Baseline), during Vibration and during the Recovery Stage for each test. The mean SBF in each stage, the change percentages and change rates of SBF in Vibration and Recovery stage among three tests were compared and analyzed for both diabetic and healthy subjects.Results: For diabetic subjects, the SBF was significantly increased in both Vibration and Recovery Stage with local intermittent vibrations (LIV1 and LIV2), but not with LCV. However, there was no significant difference in change percentage and change rate of SBF in diabetic subjects across the three tests. For healthy subjects, all vibration interventions significantly increased the SBF in the Vibration Stage and in the first 1.5 min of the Recovery Stage. Also, the change rate of SBF during the Vibration stage in LIV1 test was significantly greater than that in LIV2 test for healthy subjects. Moreover, change percentage of SBF in Vibration stage of LIV1 test and in some periods of Recovery stages of LIV1 and LIV2 tests for diabetic subjects were lower than for healthy subjects; the absolute change rate of SBF in LIV1 test for diabetic subjects was also lower than for healthy subjects.Conclusion: These findings suggest that both LIV1 and LIV2 may effectively improve SBF in the feet of diabetic people, but LCV may not achieve the same level of vasodilatation. The diabetic subjects were also found to have a lower SBF response to applied vibration than the healthy subjects.

We investigated the effects of vibration (35?Hz, 45?Hz and 55?Hz) as countermeasure locally applied to unloading hind limbs on bone, muscle and Achilles tendon. 40 female Sprague Dawley rats were divided into 5 groups (n=8, each): tail-suspension (TS), TS plus 35?Hz/0.3?g vibration (TSV35), TS plus 45?Hz/0.3?g vibration (TSV45), TS plus 55?Hz/0.3?g vibration (TSV55) and control (CON). After 21 days, bone mineral density (BMD) and the microstructure of the femur and tibia were evaluated by ?CT in vivo. The biomechanical properties of the femur and Achilles tendon were determined by a materials testing system. Ash weight of bone, isotonic contraction and wet weight of soleus were also investigated. 35?Hz and 45?Hz localized vibration were able to significantly ameliorate the decrease in trabecular BMD (expressed as the percentage change from TS, TSV35: 48.11%, TSV45: 31.09%), microstructure and ash weight of the femur and tibia induced by TS. Meanwhile, 35?Hz vibration significantly improved the biomechanical properties of the femur (57.24% bending rigidity and 41.66% Young?s modulus vs. TS) and Achilles tendon (45.46% maximum load and 66.67% Young?s modulus vs. TS). Additionally, Young?s modulus of the femur was highly correlated with microstructural parameters. Localized vibration was useful for counteracting microgravity-induced musculoskeletal loss. In general, the efficacy of 35?Hz was better than 45?Hz or 55?Hz in tail-suspended rats.