Hypervascularized glioblastoma is naturally sensitive to anti‐angiogenesis but suffers from low efficacy of transient vasculature normalization. In this study, a lipid‐polymer nanoparticle is synthesized to execute compartmentalized Cas9 and sgRNA delivery for a permanent vasculature editing strategy by knocking out the signal transducer and activator of transcription 3 (STAT3). The phenylboronic acid branched cationic polymer is designed to condense sgRNA electrostatically (inner compartment) and patch Cas9 coordinatively (outer compartment), followed by liposomal hybridization with angiopep‐2 decoration for blood–brain barrier (BBB) penetration. The lipid‐polymer nanoparticles can reach glioblastoma within 2 h post intravenous administration, and hypoxia in tumor cells triggers charge‐elimination and degradation of the cationic polymer for burst release of Cas9 and sgRNA, accompanied by instant Cas9 RNP assembly, yielding ≈50% STAT3 knockout. The downregulation of downstream vascular endothelial growth factor (VEGF) reprograms vasculature normalization to improve immune infiltration, collaborating with interleukin‐6 (IL‐6) and interleukin‐10 (IL‐10) reduction to develop anti‐glioblastoma responses. Collectively, the combinational assembly for compartmentalized Cas9/sgRNA delivery provides a potential solution in glioblastoma therapy.

The clinical advancement of protein-based nanomedicine has revolutionized medical professionals' perspectives on cancer therapy. Protein-based nanoparticles have been exploited as attractive vehicles for cancer nanomedicine due to their unique properties derived from naturally biomacromolecules with superior biocompatibility and pharmaceutical features. Furthermore, the successful translation of Abraxane™ (paclitaxel-based albumin nanoparticles) into clinical application opened a new avenue for protein-based cancer nanomedicine. In this mini-review article, we demonstrate the rational design and recent progress of protein-based nanoparticles along with their applications in cancer diagnosis and therapy from recent literature. The current challenges and hurdles that hinder clinical application of protein-based nanoparticles are highlighted. Finally, future perspectives for translating protein-based nanoparticles into clinic are identified.

Type 2 diabetes mellitus (T2DM), a high-incidence chronic metabolic disorder, has emerged as a global health issue, where most patients need lifelong medication. Gaining insights into molecular mechanisms involved in T2DM development is expected to provide novel strategies for clinical prevention and treatment. Growing evidence validates that non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) function as crucial regulators in multiple biological processes of T2DM, inspiring various potential targets and drug candidates. In this review, we summarize the current understanding of ncRNA roles in T2DM and discuss the potential use of ncRNAs as targets and active molecules for drug discovery.

Self-incompatibility (SI) prevents inbreeding depression in angiosperms. Camellia sinensis is an important cash crop, but breeding improvements and genetic studies of the plant are hindered by SI. However, the SI mechanism in C. sinensis remains unclear. In this study, a putative S-RNase gene (KU852488) was cloned from C. sinensis. The full-length cDNA of CsS-RNase is 1121bp, which encodes 238 amino acids. It shares the closest relationship with an S-RNase gene (ADA67883.1), which was cloned from a self-incompatibility Citrus reticulata cultivar ‘Wuzishatangju’. The expression level of CsS-RNase in the styles were 3–259 (‘Fuding Dabaicha’) and 5.6–119 (‘Zhongcha108’) times higher than the other tissues, for example petals, pollen grains, filaments and buds. And its expression rose in self-pollinated styles with 24h earlier than cross-pollinated styles. The genotypes of CsS-RNase in 10 cultivars and one breeding line of C. sinensis were analyzed. Totally, 11 polymorphic amino acid residues were identified. A single nucleotide polymorphism (SNP) marker of CsS-RNase was developed. Finally, the CsS-RNase was mapped onto a reference genetic linkage map of tea plant

STING1 is a central hub protein of CGAS-STING1 signaling which is important signaling axis to sense DNA for the host against pathogens infection through regulating type I interferon (IFN-I) production. However, excessive STING1 activation-induced overproduced IFN-I triggers tissue damage and autoimmune disorders. Thus, the activity of STING1 must be precisely regulated for immune homeostasis. Here, we discovered SESN1 (sestrin 1) as an essential negative regulator of STING1 to maintain immune homeostasis. Upon herpes simplex virus-1 (HSV-1) infection, the expression of SESN1 was downregulated, which enhanced potentiality to virus defense for host. Consistently, SESN1-deficient mice exhibited stronger ability against HSV-1 infection compared to wild-type littermates. Additionally, we found the expression of SESN1 was decreased in systemic lupus erythematosus (SLE) patients and trex1 KO mouse model of autoimmune disease. Intriguingly, the replenishment of SESN1 effectively impressed IFN-I production and autoimmune responses in the PBMCs of human SLE specimens and the trex1 KO mouse model both in vitro and in vivo. Mechanistically, SESN1 targeted STING1 and promoted STING1 autophagic degradation by facilitating the interaction of SQSTM1/p62 and STING1. Together, our study uncovers a crucial role of SESN1 for immune homeostasis to balance anti-virus and autoimmunity by regulating STING1. SESN1 might be a potential therapeutic target for infectious and autoimmune diseases.Abbreviations: BMDMs: bone marrow-derived macrophages; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; HTDNA: herring testes DNA; IFNA4: interferon alpha 4; IFNB: interferon beta; IRF3: interferon regulatory factor 3; ISD: interferon stimulatory DNA; ISGs: IFN-stimulated genes; PBMCs: peripheral blood mononuclear cells; RSAD2: radical S-adenosyl methionine domain containing 2; SLE: systemic lupus erythematosus; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1.