Biogenesis of tRNA-derived small RNAs (tsRNAs). Intron (yellow), 5’-reader (green), and 3’-trailer sequences (brown) are cleaved from pre-tRNAs to generate mature tRNAs. Angiogenin (ANG) in mammals and Ribonuclease-T2 like 1 (Rny1) in yeast cleave nucleotides in the anticodon loops (red) of tRNAs to generate 30-40 nucleotide-long tRNA-derived stress-induced RNAs (tiRNAs), also known as tRNA halves. Despite controversy, DICER, ANG, and RNase T1 were shown to cleave nucleotides in the pseudouridine (T) - or dihydrouridine (D) -loops (blue) of tRNAs to generate 5’- and 3’-tRNA-derived RNA fragments (tRFs), 14-30 nucleotides in length. Internal-tRFs (i-tRFs) are generated by multiple cleavages of tRNAs, and contain internal regions of tRNAs, which are 15-36 nucleotides in length.

N uptake and signaling pathway in plants. Plants uptake nitrate (NO₃⁻) through NRT transporters. NRT1.1 is dual affinity nitrate transporter, whose affinity is changed by phosphorylation through CIPK23 and CBL1/9. In addition to nitrate uptake, NRT1.1 generates calcium (Ca²⁺) signaling through Phospholipase c (PLC). Ca²⁺ induces CPK-dependent phosphorylation of NLP6/7 transcription factors, leading to nuclear accumulation of NLP6/7. HBI also accelerates nuclear accumulation of NLP6/7 by reducing cellular reactive oxygen species (ROS) level. Nuclear localized NLP6/7 interact with NRG2 and TCP20 to activate expression of N-responsive genes. NLP2, ANR1, and TGA1/4 act as positive regulator for N-responsive genes. In contrast, LBDs, NIGT1, and IWS1 negatively regulate expression of N-responsive genes. NRT2.1 is a high affinity nitrate transporter, and phosphorylation inactivates NRT2.1 under high N conditions. NRT2.1 phosphorylation was removed by CEPD-induced phosphatase (CEPH) under N starvation condition, activating NRT2.1 dependent nitrate uptake. Ammonium transporter 1;1 (AMT1;1) is responsible for ammonium (NH₄⁺) uptake. AMT1;1 is inactivated by phosphorylation through CIPK23 and ACTPK1 under high NH₄⁺ conditions to inhibit toxic accumulation of NH₄⁺ in cells. The figure was created with Biorender.com.

PROM1 cell signaling in cancer. The first intracellular domain of PROM1 promotes WNT-β-Catenin signaling pathway and tumorigenesis by interacting with HDAC6 (37). The C-terminal cytoplasmic domain of PROM1 activates PI3K-AKT signaling pathway and tumorigenesis by interacting with PI3K p85 (41). CSC, cancer stem cell.

Overview of the ASCs mediated anti-cancer treatments. ASCs mediated anti-cancer therapies are differentiated according to the use of MSCs, NSCs, and HSCs. Both MSCs and NSCs use the same carrier to deliver anti-cancer substances such as prodrug, oncolytic virus, exosomes, cytokines and photothermal heat. Viral transduced HSCs are localized in the bone marrow, and produce T cell progenitors that undergo normal immune cell maturation. Subsequently, immune cells expressing TCR that recognizes cancer-associated antigen, confer specific anti-cancer activity for a long time. Conjugation between HSCs and platelet adequately delivers immune checkpoint inhibitors to the bone marrow, and augments an anti-leukemia immune response.