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Currently used drugs for glioblastoma (GBM) treatments are ineffective, primarily due to the significant challenges posed by strong drug resistance, poor blood–brain barrier (BBB) permeability, and the lack of tumor specificity. Here, we report two cationic fluorescent anticancer agents (TriPEX-ClO4and TriPEX-PF6) capable of BBB penetration for efficient GBM therapy via paraptosis and ferroptosis induction. These aggregation-induced emission (AIE)-active agents specifically target mitochondria, effectively triggering ATF4/JNK/Alix-regulated paraptosis and GPX4-mediated ferroptosis. Specifically, they rapidly induce substantial mitochondria-derived vacuolation, accompanied by reactive oxygen species generation, decreased mitochondrial membrane potential, and intracellular Ca2+overload, thereby disrupting metabolisms and inducing nonapoptotic cell death. In vivo imaging revealed that TriPEX-ClO4and TriPEX-PF6successfully traversed the BBB to target orthotopic glioma and initiated effective synergistic therapy postintravenous injection. Our AIE drugs emerged as the pioneering paraptosis inducers against drug-resistant GBM, significantly extending survival up to 40 days compared to Temozolomide (20 days) in drug-resistant GBM-bearing mice. These compelling results open up new venues for the development of fluorescent anticancer drugs and innovative treatments for brain diseases.

We analyze the factors that increase the likelihood that other nations will follow China's global economic leadership. While our theoretical framework incorporates the conventional argument that China pulls in followers with economic benefits, we focus on grievances with the current global order that have the effect of pushing countries toward the rising new leader. We find that grievances about global financial instability are particularly important push factors. Our results show that countries that have experienced more financial crises, more variable capital account policies, more volatile portfolio capital outflows, and more social unrest during IMF programs are more likely to support China's global leadership than leaders of nations that have been less exposed to these problems. We find no evidence that grievances about global governance, or grievances about discriminatory US trade policies, are related to foreign support for China's global economic leadership. Overall, our evidence is consistent with the interpretation that leaders want to reform and preserve the WTO and the IMF, which have worked reasonably well for them under US leadership. At the same time, they have incentives to follow China's economic leadership on global capital flows, emphasizing long-term infrastructure and development finance over short-term flows which, under the current order, have imposed large costs on many economies. Key Words China; global leadership; international institutions; international change; international regimes; Belt and Road Initiative (BRI); International Monetary Fund (IMF); Asian Infrastructure Investment Bank (AIIB), doi: [...]

Macrophage hyperactivation is a hallmark of inflammatory diseases, yet the role of alternative polyadenylation (APA) of mRNAs in regulating innate immunity remains unclear. In this study, we focused on 3’UTR-APA and demonstrated that Nudt21, a crucial RNA-binding component of the 3’UTR-APA machinery, is significantly upregulated in various inflammatory conditions. By utilizing myeloid-specific Nudt21-deficient mice, we revealed a protective effect of Nudt21 depletion against colitis and severe hyperinflammation, primarily through diminished production of proinflammatory cytokines. Notably, Nudt21 regulates the mRNA stability of key autophagy-related genes, Map1lc3band Ulk2, by mediating selective 3’UTR polyadenylation in activated macrophages. As a result, Nudt21-deficient macrophages display increased autophagic activity, which leads to reduced cytokine secretion. Our findings highlight an unexplored role of Nudt21-mediated 3’UTR-APA in modulating macrophage autophagy and offer new insights into the modulation of inflammation and disease progression.

Simple and effective detection methods for circulating tumor cells are essential for early detection and progression monitoring of tumors. The use of DNA aptamer and bioluminescence is expected to be a key tool for the simple, effective, and sensitive detection of tumor cells. Herein, we designed multifunctional protein nanoparticles for the detection of tumor cells using DNA aptamer and bioluminescence. Fusion proteins (ELP-poly(d)-POIs), composed of elastin-like polypeptide (ELP) fused with protein of interests (POIs) via poly(aspartic acid) (poly(d)), formed the protein nanoparticles based on the temperature responsivity of ELP sequences, leading to multiply displayed POIs on the protein nanoparticles. In the present study, we focused on porcine circovirus type 2 replication initiation protein (Rep), which covalently conjugated with DNA aptamers, and NanoLuc luciferase (Nluc), which emitted a strong bioluminescence, as POIs. ELP-poly(d)-Rep and ELP-poly(d)-Nluc were constructed and formed the protein nanoparticles with multiply displayed Nluc and Rep (DNA aptamer) that amplified the bioluminescence signal and tumor recognition ability. Mucin-1 (MUC1)-overexpressing human breast tumor MCF7 cells and MUC1-recognizing aptamer (MUC1 aptamer) were selected as models. The MUC1 aptamer-conjugated protein nanoparticles exhibited a 13.7-fold higher bioluminescence signal to MCF-7 cells than to human embryonic kidney 293 (HEK293) cells, which express low levels of MUC1. Furthermore, the protein nanoparticles could detect up to 70.7 cells/mL of MCF-7 cells from a cell suspension containing HEK-293. The protein nanoparticles with multiple Rep and Nluc show a great potential as a material for detecting CTCs.

Chirality widely exists in nature and is closely related to the origin of life. The basic structure of all organisms is composed of chiral molecules, and biological systems have high selectivity to chiral biomolecules. Moreover, with an in-depth understanding of the origin of chiral nanomaterials, the potential applications of chiral nanomaterials in the fields of biotherapy, catalysis, and medicine have become a hot topic of research. This review discusses the different types of chiral nanomaterials and analyzes the chiral mechanism. The application of nanomaterials in chiral testing, cell differentiation, gene shearing, and biological therapy is also discussed. The potentials for and challenges of chiral nanomaterials in the field of biomedicine and proposed application strategies and prospects for the future of chiral nanomaterials in biomedicine based on the existing problems are reported.

The preparation of self-assembled porphyrins with orderly stacked nanostructures for emulating natural photosynthesis has stimulated extensive efforts to optimize the energy conversion efficiency. However, the elucidation of how orderly stacked structures promote photocatalysis at the molecular level remains a great challenge. Here, unique porphyrin nanoleaves with designed and ordered structure are synthesized and show a hydrogen evolution rate higher than that of commercial powder. Photodeposition of cocatalysts and Kelvin probe force microscopy measurement suggest selective aggregation of photogenerated electrons and holes at different active sites. Combined with theoretical calculations, we find that the orderly packing changes molecular symmetry and induces a molecular dipole, which increases linearly along the π–π stacking direction and forms a strong built-in electric field. The built-in electric field drives photogenerated electrons and holes for the unique crossed transportation along different directions. These findings reveal how orderly stacked structures promote photocatalysis and provide a novel approach for highly efficient water splitting.

This review summarized the fabrication strategy using circularly polarized light as a chiral source to construct chiral materials.The potential applications of chiral nanomaterials driven by circularly polarized light in different fields are summarized, explained by representative examples.The potential challenges of circularly polarized light-enabled chiral materials are outlined and future research directions are outlooked.