Summary Arabidopsis cryptochrome 1 (CRY1) is a blue light receptor distributed in the nucleus and cytoplasm. The nuclear CRY1, but not cytoplasmic CRY1, mediates blue light inhibition of hypocotyl elongation. However, the photobiochemical mechanisms distinguishing the CRY1 protein in the two subcellular compartments remains unclear. Here we show that the nuclear CRY1, but not the cytoplasmic CRY1, is regulated by phosphorylation, polyubiquitination and 26S proteasome‐dependent proteolysis in response to blue light. The blue light‐dependent CRY1 degradation is observed only under high fluences of blue light. The nuclear specificity and high fluence dependency of CRY1 explain why this photochemical regulatory mechanism of CRY1 was not observed previously and it further supports the hypothesis that CRY1 is a high light receptor regulating photomorphogenesis. We further show that the nuclear CRY1, but not cytoplasmic CRY1, undergoes blue light‐dependent phosphorylation by photoregulatory protein kinase 1 (PPK1) followed by polyubiquitination by the E3 ubiquitin ligase Cul4COP1/SPAs, resulting in the blue light‐dependent proteolysis. Both phosphorylation and ubiquitination of nuclear CRY1 are inhibited by blue‐light inhibitor of cryptochromes 1 (BIC1), demonstrating the involvement of photo‐oligomerization of the nuclear CRY1. These finding reveals a photochemical mechanism that differentially regulates the physiological activity of the CRY1 photoreceptor in distinct subcellular compartments.

An investigation into a novel in-vivo PMMA (polymethyl methacrylate) plastic fiber-optic dosimeter for monitoring low doses of ionizing radiotherapy radiation in real time and for integrating measurements is presented. The fabricated optical fiber tip possessed an embedded structure. A scintillation material, terbium-doped gadolinium oxysulfide (Gd 2 O 2 S:Tb), capable of emitting visible light at around 545 nm which is ideal for transmission through the PMMA when exposed to ionizing radiation was embedded in the PMMA plastic fiber. The dose rate of incident ionizing radiation is measured by analyzing the signal intensity emitted from the scintillation material which propagates through the fiber to a distal MPPC (multi-pixel photon counter). The dosimeter exhibits good repeatability with an excellent linear relationship between the fiber-optic dosimeter output and the absorbed radiation dose with an outstanding isotropic response in its radial angular dependence. "Characterization of a fiber-optic-coupled radioluminescent detector for application in the mammography energy range," Med. Phys. 34(6), 2220-2227 (2007). 7. T. Aoyama, S. Koyama, and C. Kawaura, "An in-phantom dosimetry system using pin silicon photodiode radiation sensors for measuring organ doses in x-ray CT and other diagnostic radiology," Med. Phys. 29(7), 1504-1510 (2002). 8. A. S. Beddar, T. R. Mackie, and F. H. Attix, "Water-equivalent plastic scintillation detectors for high-energy beam dosimetry: I. physical characteristics and theoretical consideration," Phys. Med. Biol. 37(10), 1883-1900 (1992). 9. A. S. Beddar, T. R. Mackie, and F. H. Attix, "Water-equivalent plastic scintillation detectors for high-energy beam dosimetry: II. properties and measurements," Phys. Med. Biol. 37(10), 1901-1913 (1992). 10. M. A. Clift, R. A. Sutton, and D. V. Webb, "Dealing with Cerenkov radiation generated in organic scintillator dosimeters by bremsstrahlung beams," Phys. Med. Biol. 45(5), 1165-1182 (2000). #254911Received 2

A novel real-time optical fibre X-Ray dosimeter for monitoring the radiation pulses delivered from a clinical Linear Accelerator (Linac) is presented. The primary focus of the sensor is to measure low doses of ionising X-ray radiation in real-time (limited to 0.1 ms gate time of the detector). The sensor tip material scintillates upon exposure to X-ray energy and the resultant low level visible light signal is coupled to a PMMA (poly methyl methacrylate) plastic optical fibre, used to guide it towards a distal Avalanche Photodiode based detector. The detector measures the low level scintillating light from the sensor thereby converting the ionizing radiation energy to a measurable signal with a time resolution of 0.1 ms. Results show that the scintillating optical fibre X-ray dosimeter is capable of capturing the individual X-Ray pulses delivered by the Linac during normal operation. Further examination of the results demonstrates that the sensor is capable of measuring dose rate and hence dose with a linearity (R 2 = 0.9995-0.9999) and in a highly repeatable manner for dose rates in the range 100 to 600 Monitor Units/ Min (MU/Min).

With the economy's globalization and the population's aging, cancer has become the leading cause of death in most countries. While imposing a considerable burden on society, the high morbidity and mortality rates have continuously prompted researchers to develop new oncology treatment options. Anti-tumor regimens have evolved from early single surgical treatment to combined (or not) chemoradiotherapy and then to the current stage of tumor immunotherapy. Tumor immunotherapy has undoubtedly pulled some patients back from the death. However, this strategy of activating or boosting the body's immune system hardly benefits most patients. It is limited by low bioavailability, low response rate and severe side effects. Thankfully, the rapid development of nanotechnology has broken through the bottleneck problem of anti-tumor immunotherapy. Multifunctional nanomaterials can not only kill tumors by combining anti-tumor drugs but also can be designed to enhance the body's immunity and thus achieve a multi-treatment effect. It is worth noting that the variety of nanomaterials, their modifiability, and the diversity of combinations allow them to shine in antitumor immunotherapy. In this paper, several nanobiotics commonly used in tumor immunotherapy at this stage are discussed, and they activate or enhance the body's immunity with their unique advantages. In conclusion, we reviewed recent advances in tumor immunotherapy based on nanomaterials, such as biological cell membrane modification, self-assembly, mesoporous, metal and hydrogels, to explore new directions and strategies for tumor immunotherapy.

An inorganic scintillating material plastic optical fiber (POF) dosimeter for measuring ionizing radiation during radiotherapy applications is reported. It is necessary that an ideal dosimeter exhibits many desirable qualities, including water equivalence, energy independence, reproducibility, dose linearity. There has been much recent research concerning inorganic dosimeters. However, little reference has been made to date of the depth-dose characteristics of dosimeter materials. In the case of inorganic scintillating materials, they are predominantly non water-equivalent, with their effective atomic weight (Z) being typically much greater than that of water. This has been a barrier in preventing inorganic scintillating material dosimeter from being used in actual clinical applications. In this paper, we propose a parallel-paired fiber light guide structure to solve this problem. Two different inorganic scintillating materials are embedded separately in the parallel-paired fiber. It is shown that the information of water depth and absorbed dose at the point of measurement can be extracted by utilizing their different depth-dose properties.