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Epigenetic regulation plays a fundamental role in controlling gene expression and maintaining cellular identity. Among epigenetic processes, the translocation of methyltransferases is critical for the modification of chromatin structure and transcriptional activity. The regulation of these translocation events and the mechanisms involved are complex, yet critical for understanding and manipulating epigenetic states. Therefore, novel strategies are required for detecting and visualizing the movement and interaction of methyltransferases within cells. Using enhancer of zeste homolog 2 (EZH2) methyltransferase as an example, a bifunctional compound capable of both monitoring and disrupting its translocation process is developed by targeting the protein-protein interaction (PPI) between embryonic ectoderm development (EED) and EZH2. The Ir(III) complex 1 bound enthalpically to EED and effectively inhibited the methyltransferase activity of EZH2. Moreover, disruption of the EED-EZH2 PPI led to increased transcriptional activity of P21 and P27, resulting in the suppression of triple-negative breast cancer (TNBC) cell proliferation. Excitingly, 1 suppressed tumor metastasis in a TNBC mouse model in vivo. To our knowledge, complex 1 is the first metal-based bifunctional therapeutic agent designed to probe and inhibit the EED-EZH2 PPI, highlighting the feasibility and significance of using metal complexes to monitor and influence methyltransferase translocations for therapeutic applications.

This study advances sustainable pharmaceutical research for endometriosis by developing in vitro 3D cell culture models of endometriotic pathophysiology that allow antifibrotic drug candidates to be tested. Fibrosis is a key aspect of endometriosis, yet current cell models to study it remain limited. This work aims to bridge the translational gap between in vitro fibrosis research and preclinical testing of non-hormonal drug candidates. When grown in a 3D matrix of sustainably produced silk protein functionalized with a fibronectin-derived cell adhesion motif (FN-silk), endometrial stromal and epithelial cells respond to transforming growth factor beta-1 (TGF-β1) in a physiological manner as probed at the messenger RNA (mRNA) level. For stromal cells, this response to TGF-β1 is not observed in spheroids, while epithelial cell spheroids behave similarly to epithelial cell FN-silk networks. Pirfenidone, an antifibrotic drug approved for the treatment of idiopathic pulmonary fibrosis, reverses TGF-β1-induced upregulation of mRNA transcripts involved in fibroblast-to-myofibroblast transdifferentiation of endometrial stromal cells in FN-silk networks, supporting pirfenidone's potential as a repurposed non-hormonal endometriosis therapy. Overall, endometrial stromal cells cultured in FN-silk networks-which are composed of a sustainably produced, fully defined FN-silk protein-recapitulate fibrotic cellular behavior with high fidelity and enable antifibrotic drug testing.

The specific targeting of intracellular proteins or organelles by magnetic nanoparticles (MNPs) is a major challenge in nanomedicine, as most MNPs are internalized by cells through endocytosis and remain trapped inside small intracellular vesicles, limiting their ability to reach intracellular components. Furthermore, this phenomenon limits their heating capacity in magnetic hyperthermia, and therefore their potential for cancer treatment. This study presents a strategy based on an original double functionalization of MNPs, with polyhistidine peptides (PHPs) triggering endosomal escape and antibodies targeting specific cytosolic proteins. Negatively charged γ-Fe₂O₃@SiO₂ MNPs with diameter smaller than 50 nm are functionalized with zwitterionic and thiol groups at their surface. These sulfhydryl groups are used to graft PHPs through a labile link, allowing the peptide to be released from the MNPs' surface once in the cytosolic reductive environment. This severing avoids any interaction between these peptides and intracellular components, which can hinder MNPs' intracellular mobility. The second MNPs' surface functionalization is performed through a non-labile link with antibodies targeting specific cytosolic proteins, namely HSP27 thermosensitive proteins, for this inaugural proof of concept. Bi-functionalized MNPs are able to successfully target the intracellular protein of interest, opening the door to promising biomedical applications of MNPs, in cellular engineering and magnetic hyperthermia.

The porphyrin-based hydrogen-bonded organic framework (HOF) offers a superior platform for decoding electrochemiluminescence (ECL) via controlling charge transfer due to its higher solubility, chemical stability, and tunable framework behavior. In this research, three kinds of HOFs including TDPP-HOF, TCPP-HOF, and TCNPP-HOF are synthesized based on a porphyrin tectonic plate decorated with 2,4-diaminotriazinyl (DAT), carboxyl, and nitrile moieties to study their ECL performances. The hydrazine as the coreactant can trigger TDPP-HOF at the low-excited positive potential to generate 15.8- and 112.9-fold enhancement in ECL signal than TCNPP-HOF and TCPP-HOF. Experimental results and density functional theory calculations verify that TDPP-HOF with a lower bandgap and a larger binding energy (ΔE) between coreactant and HOF is beneficial to intrareticular charge transfer (ICT), facilitating the enhancement of ECL performance. These results indicate that the peripheral substituents can establish a specialized outer-sphere microenvironment around the porphyrin center to tune both the HOF activity and the ECL performance. As a proof of concept, a simple TDPP-HOF-based ECL sensor is constructed to sensitively detect phenolic compounds. This research provides a new avenue for improving the ECL performance via modulating the outer-sphere microenvironment of HOFs.

The metal organic framework (MOF) MIP-177(Ti) is under the spotlight for its robust photo-response and stability. This MOF can be synthesized in forms: MIP-177(Ti)-LT (LT: low temperature) and MIP-177(Ti)-HT (HT: high temperature). The MIP-177(Ti)-LT version comprises of Ti₁₂O₁₅ units interconnected by 3,3',5,5'-tetracarboxydiphenylmethane (mdip) ligands and interconnecting formate groups. Upon high temperature treatment, MIP-177(Ti)-LT loses its formate groups, thus rearranging into a continuous 1-D chain of Ti₆O₉ units leading to the MIP-177(Ti)-HT. Based on this 1-D connected structure, one should expect a higher catalytic activity of MIP-177(Ti)-HT. Nevertheless, the hydrogen evolution reaction photoactivity assessment clearly indicates the opposite. Combining transient IR measurements (TRIR), TAS and DFT/TD-DFPT calculations unveils the reasons for this situation. The TRIR measurements evidence that the photoinduced electrons are located in the inorganic part, while the holes are in the mdip ligand. The longer lifetime of MIP-177(Ti)-LT is mapped onto a slower decay of the Ti-O related peaks. A reversible change in the coordination of the carboxylate groups from a bidentate to a monodentate coordination is observed only in MIP-177(Ti)-LT. Complementary DFT and TD-DFPT simulations demonstrate a higher electron delocalization on the inorganic part for MIP-177(Ti)-LT (hence, enhanced mobility and slower recombination), thus explaining its superior photocatalytic activity.

Van der Waals (vdW) chalcogenide-based flexible thermoelectric devices hold great promise for wearable electronics. However, intrinsic vdW chalcogenides that combine high flexibility with superior thermoelectric figures of merit (ZT) remain extremely rare. Consequently, there is an urgent need to develop methods capable of high-throughput screening to identify potential vdW chalcogenides with both robust flexibility and favorable ZT value. In this study, over 1000 vdW chalcogenides are high-throughput screened for their flexibility and ZT values. Flexibility is evaluated using the previously developed deformability factor, while ZT values are predicted using a machine learning model. Several candidates with large deformability and high ZT are successfully identified. Among these, NbSe₂Br₂ emerges as the top-performing material. Further first-principles calculations reveal that it achieves a maximum ZT value of 1.35 at 1000 K, the highest reported so far among flexible inorganic thermoelectric materials. Its power factor value of 8.1 µW cm^-1K^-2 at 300 K also surpasses most organic and inorganic flexible thermoelectric materials. The high ZT_max is mainly contributed by the extremely low thermal conductivity and the high Seebeck coefficient along the out-of-plane direction at high temperatures. The study offers new material options for the development and application of flexible thermoelectric devices based on layered chalcogenides.

Potassium-ion batteries (KIBs) have emerged as a promising alternative to lithium-ion batteries due to the abundance and low cost of potassium resources. Coupled with commercial graphite anode, KIBs have great potential for the next-generation large-scale electrochemical energy storage devices. However, graphite anode in KIBs suffers from rapid capacity decay in commercial "potassium hexafluorophosphate (KPF₆) + ethylene carbonate (EC)" electrolytes. These issues can be addressed through electrolyte engineering, which has been proven effective in improving graphite performance. This review explores the underlying mechanisms of K⁺ storage in graphite, the challenges of electrolyte design, and the recent advancements in electrolyte engineering for graphite anode optimization in KIBs.

As a promising material, ionogels have garnered increasing interest in various applications including flexible electronics and energy storage. However, most existing ionogels suffer from poor mechanical properties. Herein, an effective and universal strategy is reported to toughen ionogels by freezing the polymer network via network design. As a proof of concept, an ionogel is readily prepared by copolymerization of isobornyl acrylate (IBA) and ethoxyethoxyethyl acrylate (CBA) in the presence of ionic liquid, resulting in a bicontinuous phase-separated structure. The rigid, ionic liquid-free PIBA segments remain frozen at service temperature and serve as a load-bearing phase to toughen ionogels, while the flexible PCBA phases maintain high ionic liquid content. As a result, the mechanical properties of ionogels are noticeably improved, showing high rigidity (48.5 MPa), strength (4.19 MPa), and toughness (8.19 MJ · m^-3). Moreover, ionogels also exhibit remarkable thermo-softening performance, strong adhesiveness, high conductivity, shape memory properties, and satisfactory biocompatibility. When used as an ionic skin, the ionogel can not only respond to different deformation but also accurately and consistently detect body motions over long periods. This novel strategy in toughening ionogels can pave the way for the development of various tough and stable ionotronic devices.

Using entire tumor cells or tissues that display both common and patient-specific antigens can potentially trigger a comprehensive and long-lasting anti-tumor immune response. However, the limited immunogenicity, low uptake efficiency, and susceptibility to degradation of whole-component antigens present significant challenges. In this study, we employed tumor lysates (TLs) as whole-component antigens, in conjunction with MgAl-layered double hydroxide (MA) as nanoadjuvants and Mn²⁺ as immunostimulants, to create personalized MMAT (Mn²⁺-MA-TLs) nanovaccines. After subcutaneous injection of MMAT nanovaccines, the high local concentrations of TLs and Mn²⁺ facilitated the recruitment and activation of antigen-presenting cells (APCs), thereby inducing a robust adaptive immune response. Remarkably, MMAT nanovaccines enabled lysosomal escape, enhanced antigen cross-presentation, and activated the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in APCs. Furthermore, MMAT nanovaccines, when combined with the anti-TIGIT monoclonal antibody (aTIGIT), an immune checkpoint inhibitor, not only stimulated T-cell-based adaptive anti-tumor immune responses but also activated the NK-cell-based innate anti-tumor immunity, effectively suppressing tumor growth, recurrence, and metastasis. Thus, the ternary MMAT nanovaccines developed here introduced a pioneered paradigm for the rapid preparation of whole-component tumor antigens with nanoadjuvants and immunostimulants into nanovaccines, offering new prospects for clinical immunotherapies.

The sustainable utilization of natural resources and growing demand for various electronic devices have promoted the development of safe, stable, and rechargeable aqueous zinc-ion batteries (AZIBs). However, a stable cathode material is crucial for ZIBs in an aqueous electrolyte, since it is more difficult for divalent Zn²⁺ to be reversibly inserted and extracted between active materials than it is for monovalent metal ions. In this work, a tailored multi-defect MXene, Mo_1.74CT_z, of a complete chemical formula of Mo_1.74±0.06CO_0.95±0.02(OH)_0.63±0.01F_0.3±0.03.0.2±0.05H₂O_ads (Mo_1.74CT_z), is assembled as cathode in AZIBs. It achieved 75% capacity retention and nearly 100% Coulombic efficiency even after up to 100 000 cycles as the intrinsic structural stability and many vertical holes of the Mo_1.74CT_z MXene contributed to alleviating the MXene collapse under repeated charge and discharge. Meanwhile, the Mo_1.74CT_z-based AZIBs exhibited good performance with a specific capacity of 200 mAh g^-1 at a current density of 0.2 A g^-1, which greatly exceeds previous reports of pure MXene-based cathodes in AZIBs. This work will aid in finding new solutions for sustainable energy development, which will pave the way for AZIBs as an alternative to lithium-ion batteries (LIBs) in the future.