Immunoregulatory Engineering of Semiconducting Charge-Reversal Nanoantioxidant for Ameliorating Cancer Radioimmunotheranostics.

Radiotherapy (RT) is a crucial clinical modality for cancer. However, nonselectivity, toxicity to normal tissues, and radio-resistance severely limit RT applications. This study develops a versatile X-ray theranostic nano-antioxidant (XTN) to prevent normal tissues from oxidative damage and induce systematic and robust anticancer immunity. XTN owns NIR-II photoacoustic (PA) imaging properties for precise discrimination of the tumor margin through, thereby improving the accuracy of RT. Additionally, XTN is a nano-antioxidant to enhance the cell viability of normal cells after irradiation. Most importantly, XTN scavenges reactive oxygen species (ROS) in the TME to preserve the stimulatory activity of released high mobility group protein B1 to dendritic cells (DCs) and recover T cells' immune function. Meanwhile, XTN achieves charge-reversal specifically releasing an immunomodulator (demethylcantharidin, DMC) in the acidic TME. Moreover, the specifically released DMC inhibits protein phosphatase-2A activity and reduces regulatory T cell (Treg) differentiation. In the bilateral 4T1 tumor model, XTN-mediated radioimmunotherapy remarkably boosts a systemic antitumor immune response and induces durable immunological memory against tumor growth.

Gene co-expression network analysis in areca floral organ and the potential role of the AcMADS17 and AcMADS23 in transgenic Arabidopsis.

Areca catechu L., a monocot belonging to the palm family, is monoecious, with female and male flowers separately distributed on the same inflorescence. To discover the molecular mechanism of flower development in Areca, we sequenced different floral samples to generate tissue-specific transcriptomic profiles. We conducted a comparative analysis of the transcriptomic profiles of apical sections of the inflorescence with male flowers and the basal section of the inflorescence with female flowers. Based on the RNA sequencing dataset, we applied weighted gene co-expression network analysis (WGCNA) to identify sepal, petal, stamen, stigma and other specific modules as well as hub genes involved in specific floral organ development. The syntenic and expression patterns of AcMADS-box genes were analyzed in detail. Furthermore, we analyzed the open chromatin regions and transcription factor PI binding sites in male and female flowers by assay for transposase-accessible chromatin sequencing (ATAC-seq) assay. Heterologous expression revealed the important role of AcMADS17 and AcMADS23 in floral organ development. Our results provide a valuable genomic resource for the functional analysis of floral organ development in Areca.

Toward Type I/II ROS Generation Photoimmunotherapy by Molecular Engineering of Semiconducting Perylene Diimide.

As prospective phototheranostic agents for cancer imaging and therapy, semiconducting organic molecule-based nanomedicines are developed. However, near-infrared (NIR) emission, and tunable type I (O2 • -) and type II (1O2) photoinduced reactive oxygen species (ROS) generation to boost cancer photoimmunotherapy remains a big challenge. Herein, a series of D-π-A structures, NIR absorbing perylene diimides (PDIs) with heavy atom bromide modification at the bay position of PDIs are prepared for investigating the optimal photoinduced type I/II ROS generation. The heavy atom effect has demonstrated a reduction of molecular ∆EST and promotion of the intersystem crossing processes of PDIs, enhancing the photodynamic therapy (PDT) efficacy. The modification of three bromides and one pyrrolidine at the bay position of PDI (TBDT) has demonstrated the best type I/II PDT performance by batch experiments and theoretical calculations. TBDT based nanoplatforms (TBDT NPs) enable type I/II PDT in the hypoxic tumor microenvironment as a strong immunogenic cell death (ICD) inducer. Moreover, TBDT NPs showing NIR emission allow in vivo bioimaging guided phototherapy of tumor. This work uses novel PDIs with adjustable type I/II ROS production to promote antitumor immune response and accomplish effective tumor eradication, consequently offering molecular guidelines for building high-efficiency ICD inducers.

Transcriptome and targeted metabolomic integrated analysis reveals mechanisms of B vitamin accumulation in Areca catechu nut development.

Areca catechu is well known as a medicinal plant that has high nutritional and medicinal benefits. However, the metabolism and regulatory mechanism of B vitamins during areca nut development remain largely unclear. In this study, we obtained the metabolite profiles of six B vitamins during different areca nut developmental stages by targeted metabolomics. Furthermore, we obtained a panoramic expression profile of genes related to the biosynthetic pathway of B vitamins in areca nuts at different developmental stages using RNA-seq. In total, 88 structural genes related to B vitamin biosynthesis were identified. Furthermore, the integrated analysis of B vitamin metabolism data and RNA-seq data showed the key transcription factors regulating thiamine and riboflavin accumulation in areca nuts, including AcbZIP21, AcMYB84, and AcARF32. These results lay the foundation for understanding metabolite accumulation and the molecular regulatory mechanisms of B vitamins in A. catechu nut.

Genome-Wide Identification of PIN and PILS Gene Families in Areca catechu and the Potential Role of AcPIN6 in Lateral Brace Root Formation.

PIN-FORMED (PIN) and PIN-LIKES (PILS) are two families of auxin transporters that control the directional cell-to-cell transport and intracellular accumulation of auxin, thereby influencing plant growth and development. Most knowledge of PINs and PILSs was obtained from the dicot model plant Arabidopsis thaliana. Here, we focus on the distribution and expression of the PIN and PILS gene families in areca palm (Areca catechu), a monocot tree. The whole genomic dataset of areca palm was used to identify twelve AcPINs and eight AcPILSs, and a phylogenetic tree was constructed of PINS and PILS together with several other palm species, including the date palm (Phoenix dactylifera), oil palm (Elaeis guineensis), and coconut (Cocos nucifera). We further analyzed the expression patterns of AcPIN and AcPILS in areca palm, and found that AcPIN6 displayed an extremely high transcriptional abundance in the brace roots and was extremely stimulated in the lateral root primordium. This result implies that AcPIN6 plays an important role in the growth and formation of brace roots, especially in lateral root initiation. We also overexpressed AcPIN6 and AcPIN6-eGFP in Arabidopsis, and the results revealed that the PIN6 localized on the plasma membrane and affected auxin-related phenomena. Taken together, we analyzed the evolutionary relationships of PINs and PILSs in palm species, and the roles of PIN6 in areca palm root formation. The results will improve the understanding of root system construction in large palm trees.