Radiotherapy (RT) is a mainstay treatment for many types of cancer, although it is still a large challenge to enhance radiation damage to tumor tissue and reduce side effects to healthy tissue. Radiosensitizers are promising agents that enhance injury to tumor tissue by accelerating DNA damage and producing free radicals. Several strategies have been exploited to develop highly effective and low-toxicity radiosensitizers. In this review, we highlight recent progress on radiosensitizers, including small molecules, macromolecules, and nanomaterials. First, small molecules are reviewed based on free radicals, pseudosubstrates, and other mechanisms. Second, nanomaterials, such as nanometallic materials, especially gold-based materials that have flexible surface engineering and favorable kinetic properties, have emerged as promising radiosensitizers. Finally, emerging macromolecules have shown significant advantages in RT because these molecules can be combined with biological therapy as well as drug delivery. Further research on the mechanisms of radioresistance and multidisciplinary approaches will accelerate the development of radiosensitizers.

Artificially improving traits of cultivated alfalfa (Medicago sativa L.), one of the most important forage crops, is challenging due to the lack of a reference genome and an efficient genome editing protocol, which mainly result from its autotetraploidy and self-incompatibility. Here, we generate an allele-aware chromosome-level genome assembly for the cultivated alfalfa consisting of 32 allelic chromosomes by integrating high-fidelity single-molecule sequencing and Hi-C data. We further establish an efficient CRISPR/Cas9-based genome editing protocol on the basis of this genome assembly and precisely introduce tetra-allelic mutations into null mutants that display obvious phenotype changes. The mutated alleles and phenotypes of null mutants can be stably inherited in generations in a transgene-free manner by cross pollination, which may help in bypassing the debate about transgenic plants. The presented genome and CRISPR/Cas9-based transgene-free genome editing protocol provide key foundations for accelerating research and molecular breeding of this important forage crop.

been widely used as promising agents for multifunctional blood vessel imaging and tumor imaging. All these agents with well-defined surface chemistry performed good stability and high fluorescence in physiological environment and can be used for NIR-II imaging in vivo. However, due to the large hydrodynamic size, most of inorganic nanoparticles still cannot be excreted rapidly by kidney. The accumulation of these materials in body may induce potential liver toxicity, which prevents their further applications in clinical medicine. Moreover, the organic materials, such as conjugated polymer fluorophores [7] and small molecules, [8] have improved biocompatibility, showing great potential in clinical translation. Nevertheless, the fluorescence quantum yield (QY) of these materials is still far from ideal. Thus, it is desirable to design an NIR-II agent with high QY as well as high efficiency in renal clearance for wide biological and clinical applications. Here, we present a bright Au 25 cluster with the unique cage-like structure that can emit NIR-II fluorescence at 1100-1350 nm by the charge transfer between ligand and gold core. [9] Metal doping further increases fluorescence QY of Au 25 clusters. The time-resolved brain blood flow shows significant differences between healthy and injured brain, which allow us to distinguish the lipopolysaccharides (LPS) induced brain injury and stroke in vivo. Meanwhile, real-time cancer metastasis is monitored by NIR-II imaging. Importantly, the ultrasmall hydrodynamic size of 3.2 nm allows the gold clusters to cross the glomerular filtration and be excreted fast by Near-infrared II (NIR-II) imaging at 1100-1700 nm shows great promise for medical diagnosis related to blood vessels because it possesses deep penetration and high resolution in biological tissue. Unfortunately, currently available NIR-II fluorophores exhibit slow excretion and low brightness, which prevents their potential medical applications. An atomic-precision gold (Au) cluster with 25 gold atoms and 18 peptide ligands is presented. The Au 25 clusters show emission at 1100-1350 nm and the fluorescence quantum yield is significantly increased by metal-atom doping. Bright gold clusters can penetrate deep tissue and can be applied in in vivo brain vessel imaging and tumor metastasis. Time-resolved brain blood-flow imaging shows significant differences between healthy and injured mice with different brain diseases in vivo. High-resolution imaging of cancer metastasis allows for the identification of the primary tumor, blood vessel, and lymphatic metastasis. In addition, gold clusters with NIR-II fluorescence are used to monitor highresolution imaging of kidney at a depth of 0.61 cm, and the quantitative measurement shows 86% of the gold clusters are cleared from body without any acute or long-term toxicity at a dose of 100 mg kg −1 .

microRNAs (miRNAs) are a class of negative regulators that take part in many processes such as growth and development, stress responses, and metabolism in plants. Recently, miRNAs were shown to function in plant nutrient metabolism. Moreover, several miRNAs were identified in the response to nitrogen (N) deficiency. To investigate the functions of other miRNAs in N deficiency, deep sequencing technology was used to detect the expression of small RNAs under N-sufficient and -deficient conditions. The results showed that members from the same miRNA families displayed differential expression in response to N deficiency. Upon N starvation, the expression of miR169, miR171, miR395, miR397, miR398, miR399, miR408, miR827, and miR857 was repressed, whereas those of miR160, miR780, miR826, miR842, and miR846 were induced. miR826, a newly identified N-starvation-induced miRNA, was found to target the AOP2 gene. Among these N-starvation-responsive miRNAs, several were involved in cross-talk among responses to different nutrient (N, P, S, Cu) deficiencies. miR160, miR167, and miR171 could be responsible for the development of Arabidopsis root systems under N-starvation conditions. In addition, twenty novel miRNAs were identified and nine of them were significantly responsive to N-starvation. This study represents comprehensive expression profiling of N-starvation-responsive miRNAs and advances our understanding of the regulation of N homeostasis mediated by miRNAs.