Dipeptidylpeptidase-4-targeted activatable fluorescent probes visualize senescent cells.

Senescent cells promote cancer development and progression through chronic inflammation caused by a senescence-associated secretory phenotype (SASP). Although various senotherapeutic strategies targeting senescent cells have been developed for the prevention and treatment of cancers, technology for the in vivo detection and evaluation of senescent cell accumulation has not yet been established. Here, we identified activatable fluorescent probes targeting dipeptidylpeptidase-4 (DPP4) as an effective probe for detecting senescent cells through an enzymatic activity-based screening of fluorescent probes. We also determined that these probes were highly, selectively, and rapidly activated in senescent cells during live cell imaging. Furthermore, we successfully visualized senescent cells in the organs of mice using DPP4-targeted probes. These results are expected to lead to the development of a diagnostic technology for noninvasively detecting senescent cells in vivo and could play a role in the application of DPP4 prodrugs for senotherapy.

Active alignment of receiving beam for coaxial optics in wind sensing coherent Doppler lidar using feedback control based on the processing of heterodyne-detected signal.

We have developed an active alignment of receiving beam (AARB) function for coaxial optics in wind sensing coherent Doppler lidar using feedback control based on the heterodyne-detected signal processing of backscattered light from the aerosols. The proposed method needs only the simple alignment components and contributes to the robustness for the coherent lidars with the high-power laser transmitter under the risky condition of misalignment, for example, in the airborne application. The concept, design, and evaluation results of the alignment precision are shown. The effect of the AARB is demonstrated for both cases of the hard target and soft target (i.e., wind sensing). To the best of our knowledge, this is the first demonstration of the AARB concept for the wind sensing coherent lidar.

Demonstration of the 1.53-µm coherent DIAL for simultaneous profiling of water vapor density and wind speed.

The 1.53-µm coherent differential absorption lidar (DIAL) is demonstrated for the simultaneous profiling of water vapor (H2O) density and wind speed. The optical setup is fiber-based. The wavelength locking circuit can achieve precise locking of 13.0 MHz by the combination of the line center locking to the hydrogen cyanide (HCN) absorption line and offset locking to the H2O absorption wavelength. The measurable range for the simultaneous profiling is up to 1.2 km. The DIAL-measured H2O density is compared with the one measured by an in-situ sensor. Qualitative good agreement is shown with the random error of 0.56 g/m3.

1.55-µm high-peak, high-average-power laser amplifier using an Er,Yb:glass planar waveguide for wind sensing coherent Doppler lidar.

We have developed a high-gain, high-peak-power laser amplifier at an eye-safe 1.55 µm wavelength using an Er,Yb:glass planar waveguide for wind sensing coherent Doppler lidars (CDLs). Our planar waveguide is free from stimulated Brillouin scattering and realizes high gain thanks to its multi-bounce optical-path configuration. A peak power of 5.5 kW with a pulse energy of 3.2 mJ is achieved at the repetition frequency of 4 kHz, which leads to an average power of 12.8 W. The gain is more than 23 dB. The wind sensing at more than 30 km is demonstrated with a CDL using the developed amplifier.

RNaseH2A downregulation drives inflammatory gene expression via genomic DNA fragmentation in senescent and cancer cells.

Cellular senescence caused by oncogenic stimuli is associated with the development of various age-related pathologies through the senescence-associated secretory phenotype (SASP). SASP is mediated by the activation of cytoplasmic nucleic acid sensors. However, the molecular mechanism underlying the accumulation of nucleotide ligands in senescent cells is unclear. In this study, we revealed that the expression of RNaseH2A, which removes ribonucleoside monophosphates (rNMPs) from the genome, is regulated by E2F transcription factors, and it decreases during cellular senescence. Residual rNMPs cause genomic DNA fragmentation and aberrant activation of cytoplasmic nucleic acid sensors, thereby provoking subsequent SASP factor gene expression in senescent cells. In addition, RNaseH2A expression was significantly decreased in aged mouse tissues and cells from individuals with Werner syndrome. Furthermore, RNaseH2A degradation using the auxin-inducible degron system induced the accumulation of nucleotide ligands and induction of certain tumourigenic SASP-like factors, promoting the metastatic properties of colorectal cancer cells. Our results indicate that RNaseH2A downregulation provokes SASP through nucleotide ligand accumulation, which likely contributes to the pathological features of senescent, progeroid, and cancer cells.