No abstract

Heterochromatin is a tightly packed form of chromatin that is associated with DNA methylation and histone 3 lysine 9 methylation (H3K9me). Here, we identify an H3K9me2-binding protein, Agenet domain (AGD)-containing p1 (AGDP1), in Arabidopsis thaliana. Here we find that AGDP1 can specifically recognize the H3K9me2 mark by its three pairs of tandem AGDs. We determine the crystal structure of the Agenet domain 1 and 2 cassette (AGD12) of Raphanus sativus AGDP1 in complex with an H3K9me2 peptide. In the complex, the histone peptide adopts a unique helical conformation. AGD12 specifically recognizes the H3K4me0 and H3K9me2 marks by hydrogen bonding and hydrophobic interactions. In addition, we find that AGDP1 is required for transcriptional silencing, non-CG DNA methylation, and H3K9 dimethylation at some loci. ChIP-seq data show that AGDP1 preferentially occupies long transposons and is associated with heterochromatin marks. Our findings suggest that, as a heterochromatin-binding protein, AGDP1 links H3K9me2 to DNA methylation in heterochromatin regions.

Lysosomes are an important component of the inner membrane system and participate in numerous cell biological processes, such as macromolecular degradation, antigen presentation, intracellular pathogen destruction, plasma membrane repair, exosome release, cell adhesion/migration and apoptosis. Thus, lysosomes play important roles in cellular activity. In addition, previous studies have shown that lysosomes may play important roles in cancer development and progression through the abovementioned biological processes and that the functional status and spatial distribution of lysosomes are closely related to cancer cell proliferation, energy metabolism, invasion and metastasis, immune escape and tumor-associated angiogenesis. Therefore, identifying the factors and mechanisms that regulate the functional status and spatial distribution of lysosomes and elucidating the relationship between lysosomes and the development and progression of cancer can provide important information for cancer diagnosis and prognosis prediction and may yield new therapeutic targets. This study briefly reviews the above information and explores the potential value of lysosomes in cancer therapy.

Owing to the high depth of tissue penetration, non-invasiveness, and controllability, ultrasound (US)mediated sonodynamic therapy (SDT) has shown broad application prospects for tumor treatment. However, the electron-hole separation inefficiency of sonosensitizers and the tumor hypoxia remain two major challenges limiting the effect of SDT. Here, ultrafine photoetched bismuth vanadate (BiVO 4 ) nanorods modified with DSPE-PEG 2000 (PEBVO@PEG NRs) were fabricated to achieve in situ self-supply of oxygen (O 2 ) and reactive oxygen species (ROS) for hypoxic tumor therapy. The photoetching approach could enhance the charge separation by inducing enriched oxygen vacancies on the surface of BiVO 4 , thereby improving the generation efficiency of ROS and O 2 . The PEBVO@PEG overcome the main obstacles of traditional sonosensitizers in the SDT process and show promising sonodynamic therapeutic effects, thus providing new strategies for improving the performance of sonosensitizer and hypoxic tumor elimination.

Although Wilms' tumor gene 1 (WT1) was first cloned and identified as a tumor suppressor gene in nephroblastoma, subsequent studies have demonstrated that it can also play an oncogenic role in leukemia and various solid tumors. WT1 exerts biological functions with high tissue-and cell-specificity. This article reviews the relationship between WT1 and breast cancer from two aspects: (1) clinical application of WT1, including the relationship between expression of WT1 and prognosis of breast cancer patients, and its effectiveness as a target for comprehensive therapy of breast cancer; (2) the biological effects and molecular mechanisms of WT1 in the development and progression of breast cancer, including proliferation, apoptosis, invasion, and metastasis of breast cancer cells.

Background: Multiple myeloma (MM) is a prevalent hematological malignancy. Long noncoding RNAs are correlated with the development of MM. In this project, the function of lncRNA opa interacting protein 5-antisense 1 (OIP5-AS1) in MM and the potential mechanistic pathway were explored. Methods: The expression of OIP5-AS1, microRNA (miR)-27a-3p and tuberous sclerosis 1 (TSC1) was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and Bromodeoxyuridine (BrdU) staining. And cell apoptosis was evaluated by flow cytometry assay. Cell metastasis was assessed utilizing transwell assay. Western blot analysis was employed to detect protein level. The target relation between miR-27a-3p and OIP5-AS1 or TSC1 was confirmed via dual-luciferase reporter assay and RNA immunoprecipitation assay. Tumor xenograft assay was conducted to measure the function of OIP5-AS1 in vivo. Results: The expression levels of OIP5-AS1 and TSC1 were decreased in MM, whereas miR-27a-3p was upregulated. High level of OIP5-AS1 could predict favourable prognosis of MM patients. Overexpression of OIP5-AS1 inhibited cell viability, colony formation ability, migration and invasion, induced cell cycle arrest in G1 phase and apoptosis of MM cells in vitro as well as repressed tumorigenesis in vivo. MiR-27a-3p was a target of OIP5-AS1, and reversed the impact of OIP5-AS1 on MM cells. MiR-27a-3p directly targeted TSC1. Silencing of miR-27a-3p repressed MM progression by elevating TSC1 expression. OIP5-AS1 upregulated TSC1 by sponging miR-27a-3p. Conclusion: OIP5-AS1 repressed multiple myeloma progression by regulating miR-27a-3p/TSC1 axis.

Traditional cancer treatments, surgery, chemotherapy, and radiotherapy, often suffer from severe adverse effects and high drug resistance, leading to the therapeutic efficacy are less than satisfactory. [2] To overcome these "Achilles heel," minimally invasive or noninvasive treatment regimens are being introduced in cancer treatment to promote the production of specific toxic substances within tumor while sparing normal tissues from damage. [3] Among them, sonodynamic therapy (SDT), which uses low-intensity ultrasound (US) as an excitation source to trigger sonochemical reactions for generating highly cytotoxic reactive oxygen species (ROS), has been drawing increasing attention for its high tissue-penetration and safety to human body of ultrasonic waves. [4] Despite these unparalleled advantages, SDT is still in basic research stage and has not achieved widespread clinical application, because the deficiency of sonosensitizers and the specificity of tumor microenvironment (TME) substantially hinder the continuous production of ROS. [5] A variety of sonosensitizers with excellent performance have thus been proposed to overcome this conundrum during the past decades. [6] It is worth noting that the barriers to ROS generation are diverse, such as rapid recombination of sonoexcited electrons/ holes, inherent tumor hypoxia, and high levels of glutathione Conventional sonodynamic therapy is unavoidably limited by the tumor microenvironment, although many sonosensitizers have been developed to improve them to a certain extent. Given this, a concept of sonocatalytic hydrogen evolution is proposed, which is defined as an oxygen-independent therapeutics. To demonstrate the feasibility of the concept, the narrowbandgap semiconductor bismuth sulfide (Bi 2 S 3 ) is selected as the sonocatalyst and platinum (Pt) nanoparticles are grown in situ to optimize their catalytic performance. In this nanocatalytic system, the Pt nanoparticles help to capture sonoexcited electrons, whereas intratumoral overexpressed glutathione (GSH), as a natural hole sacrificial agent, can consume sonoexcited holes, which greatly improves the charge-separation efficiency and promotes controllable and sustainable H 2 generation. Even under hypoxic conditions, the Pt-Bi 2 S 3 nanoparticles can also produce sufficient H 2 under ultrasound irradiation. Mechanistically, mitochondrial dysfunction caused by H 2 and intratumoral redox homeostasis destruction by GSH depletion synergistically damage DNA to induce tumor cells apoptosis. At the same time, the Pt nanoparticles and holes can also trigger the decomposition of hydrogen peroxide into O 2 to relieve tumor hypoxia, thus being synergistic with GSH depletion to reverse tumor immunosuppressive microenvironment. The proposed sonocatalysis-mediated therapy will provide a new direction to realize facile and efficient cancer therapy.

Hopper shape is a special type of crystal morphology. Hopper‐shaped crystals possess unique properties and show promise in many different applications. The understanding of how the building blocks (atoms, ions, and molecules) assemble into hopper‐shaped crystals and how the environmental factors influence the assembly process is critical to the properties and applications of hopper‐shaped crystals. In this review, the important interfacial instability theories that outline the underlying mechanisms for the formation of hopper‐shaped crystals are discussed. Next, the relevant experimental developments based on three categories of synthetic approaches are discussed: the growth through the control of the solute concentration, the temperature gradient, and the capping agent. At the end of the review, the applications, opportunities, and potential challenges of the hopper‐shaped crystals are discussed.