Boron/nitrogen-trapping and regulative electronic states around Ru nanoparticles towards bifunctional hydrogen production.

Developing a straightforward and general strategy to regulate the surface microenvironment of a carbon matrix enriched with N/B motifs for efficient atomic utilization and electronic state of metal sites in bifunctional hydrogen production via ammonia-borane hydrolysis (ABH) and water electrolysis is a persistent challenge. Herein, we present a simple, green, and universal approach to fabricate B/N co-doped porous carbons using ammonia-borane (AB) as a triple functional agent, eliminating the need for hazardous and explosive functional agents and complicated procedures. The pyrolysis of AB induces the regulation of the surface microenvironment of the carbon matrix, leading to the formation of abundant surface functional groups, defects, and pore structures. This regulation enhances the efficiency of atom utilization and the electronic state of the active component, resulting in improved bifunctional hydrogen evolution. Among the catalysts, B/N co-doped vulcan carbon (Ru/BNC) with 2.1 wt% Ru loading demonstrates the highest performance in catalytic hydrogen production from ABH, achieving an ultrahigh turnover frequency of 1854 min-1 (depending on the dispersion of Ru). Furthermore, this catalyst shows remarkable electrochemical activity for hydrogen evolution in alkaline water electrolysis with a low overpotential of 31 mV at 10 mA cm-2. The present study provides a simple, green, and universal method to regulate the surface microenvironment of various carbons with B/N modulators, thereby adjusting the atomic utilization and electronic state of active metals for enhanced bifunctional hydrogen evolution.

Gold core@CeO2 halfshell Janus nanocomposites catalyze targeted sulfate radical for periodontitis therapy.

The sulfate radical (SO4•-), known for its high reactivity and long lifespan, has emerged as a potent antimicrobial agent. Its exceptional energy allows for the disruption of vital structures and metabolic pathways in bacteria that are usually inaccessible to common radicals. Despite its promising potential, the efficient generation of this radical, particularly through methods involving enzymes and photocatalysis, remains a substantial challenge. Here, we capitalized on the peroxidase (POD)-mimicking activity and photocatalytic properties of cerium oxide (CeO2) nanozymes, integrating these properties with the enhanced concept of plasma gold nanorod (GNR) to develop a half-encapsulated core@shell GNRs@CeO2 Janus heterostructure impregnated with persulfate. Under near-infrared irradiation, the GNRs generate hot electrons, thereby boosting the CeO2's enzyme-like activity and initiating a potent reactive oxygen species (ROS) storm. This distinct nanoarchitecture facilitates functional specialization, wherein the heterostructure and efficient light absorption ensured continuous hot electron flow, not only enhancing the POD-like activity of CeO2 for the production of SO4•- effectively, but also contributing a significant photothermal effect, disrupting periodontal plaque biofilm and effectively eradicating pathogens. Furthermore, the local temperature elevation synergistically enhances the POD-like activity of CeO2. Transcriptomics analysis, as well as animal experiments of the periodontitis model, have revealed that pathogens undergo genetic information destruction, metabolic disorders, and pathogenicity changes in the powerful ROS system, and profound therapeutic outcomes in vivo, including anti-inflammation and bone preservation. This study demonstrated that energy transfer to augment nanozyme activity, specifically targeting ROS generation, constitutes a significant advancement in antibacterial treatment.

Designing Dual-Site Catalysts for Selectively Converting CO2 into Methanol.

The variability of CO2 hydrogenation reaction demands new potential strategies to regulate the fine structure of the catalysts for optimizing the reaction pathways. Herein, we report a dual-site strategy to boost the catalytic efficiency of CO2-to-methanol (MA) conversion. A new descriptor, τ, was initially established for screening the promising candidates with low-temperature activation capability of CO2, and sequentially a high-performance catalyst was fabricated centred with oxophilic Mo single atoms, who was further decorated with Pt nanoparticles. In CO2 hydrogenation, the obtained dual-site catalysts possess a remarkably-improved MA generation rate (0.27 mmol gcat.-1 h-1). For comparison, the singe-site Mo and Pt-based catalysts can only produce ethanol (EA) and formate acid (FA) at a relatively low reaction rate (0.11 mmol gcat.-1 h-1 for EA and 0.034 mmol gcat.-1 h-1 for FA), respectively. Mechanism studies indicate that the introduction of Pt species could create an active hydrogen-rich environment, leading to the alterations of the adsorption configuration and conversion pathways of the *OCH2 intermediates on Mo sites. As a result, the catalytic selectivity was successfully switched.

Metal-Organic Framework-Based Nanovaccine for Relieving Immunosuppressive Tumors via Hindering Efferocytosis of Macrophages and Promoting Pyroptosis and Cuproptosis of Cancer Cells.

Current cancer vaccines face challenges due to an immunosuppressive tumor microenvironment and their limited ability to produce an effective immune response. To address the above limitations, we develop a 3-(2-spiroadamantyl)-4-methoxy-4-(3-phosphoryloxy)-phenyl-1,2-dioxetane (alkaline phosphatase substrate) and XMD8-92 (extracellular signal-regulated kinase 5 inhibitor)-codelivered copper-tetrahydroxybenzoquinone (Cu-THBQ/AX) nanosized metal-organic framework to in situ-generate therapeutic vaccination. Once inside the early endosome, the alkaline phosphatase overexpressed in the tumor cells' membrane activates the in situ type I photodynamic effect of Cu-THBQ/AX for generating •O2-, and the Cu-THBQ/AX catalyzes O2 and H2O2 to •O2- and •OH via semiquinone radical catalysis and Fenton-like reactions. This surge of ROS in early endosomes triggers caspase-3-mediated proinflammatory pyroptosis via activating phospholipase C. Meanwhile, Cu-THBQ/AX can also induce the oligomerization of dihydrolipoamide S-acetyltransferase to trigger tumor cell cuproptosis. The production of •OH could also trigger the release of XMD8-92 for effectively inhibiting the efferocytosis of macrophages to convert immunosuppressive apoptosis of cancer cells into proinflammatory secondary necrosis. The simultaneous induction of pyroptosis, cuproptosis, and secondary necrosis effectively converts the tumor microenvironment from "cold" to "hot" conditions, making it an effective antigen pool. This transformation successfully activates the antitumor immune response, inhibiting tumor growth and metastasis.

Novel Spatially Asymmetric Copper Bismuthate-Mediated Augmentation of Energy Conversion to Realize "Three-Step" Tumor Suppression.

The generally undesirable bandgap and electron-hole complexation of inorganic sonosensitizers limit the efficiency of reactive oxygen species (ROS) generation, affecting the effectiveness of sonodynamic therapy (SDT). Comparatively, the novel polyvinylpyrrolidone-modified copper bismuthate (PCBO) sonosensitizers are manufactured for a "three-step" SDT promotion. In brief, first, the strong hybridization between Bi 6s and O 2p orbitals in PCBO narrows the bandgap (1.83 eV), facilitating the rapid transfer of charge carriers. Additionally, nonequivalent [CuO4]6- layers reduce crystal symmetry, confer PCBO unique piezoelectricity, and improve electron-hole separation under ultrasonic (US) excitation. This allows PCBO to convert US energy into chemical energy to produce ROS, achieving the accumulation of abundant ROS, resulting in apoptosis and tumor suppression. Concurrently, PCBO also acts as a glutathione scavenger to reduce tumor antioxidant capacity and improve efficacy. To the best of authors understanding, this study reveals PCBO as an innovative piezoelectric sonosensitizer and provides a meaningful paradigm for designing energy conversion strategies for tumor suppression.

A peroxisomal cinnamate:CoA ligase-dependent phytohormone metabolic cascade in submerged rice germination.

The mechanism underlying the ability of rice to germinate underwater is a largely enigmatic but key research question highly relevant to rice cultivation. Moreover, although rice is known to accumulate salicylic acid (SA), SA biosynthesis is poorly defined, and its role in underwater germination is unknown. It is also unclear whether peroxisomes, organelles essential to oilseed germination and rice SA accumulation, play a role in rice germination. Here, we show that submerged imbibition of rice seeds induces SA accumulation to promote germination in submergence. Two submergence-induced peroxisomal Oryza sativa cinnamate:CoA ligases (OsCNLs) are required for this SA accumulation. SA exerts this germination-promoting function by inducing indole-acetic acid (IAA) catabolism through the IAA-amino acid conjugating enzyme GH3. The metabolic cascade we identified may potentially be adopted in agriculture to improve the underwater germination of submergence-intolerant rice varieties. SA pretreatment is also a promising strategy to improve submerged rice germination in the field.

Well-defined diatomic catalysis for photosynthesis of C2H4 from CO2.

Owing to the specific electronic-redistribution and spatial proximity, diatomic catalysts (DACs) have been identified as principal interest for efficient photoconversion of CO2 into C2H4. However, the predominant bottom-up strategy for DACs synthesis has critically constrained the development of highly ordered DACs due to the random distribution of heteronuclear atoms, which hinders the optimization of catalytic performance and the exploration of actual reaction mechanism. Here, an up-bottom ion-cutting architecture is proposed to fabricate the well-defined DACs, and the superior spatial proximity of CuAu diatomics (DAs) decorated TiO2 (CuAu-DAs-TiO2) is successfully constructed due to the compact heteroatomic spacing (2-3 Å). Owing to the profoundly low C-C coupling energy barrier of CuAu-DAs-TiO2, a considerable C2H4 production with superior sustainability is achieved. Our discovery inspires a novel up-bottom strategy for the fabrication of well-defined DACs to motivate optimization of catalytic performance and distinct deduction of heteroatom synergistically catalytic mechanism.

Single-Site Nanozymes with a Highly Conjugated Coordination Structure for Antitumor Immunotherapy via Cuproptosis and Cascade-Enhanced T Lymphocyte Activity.

The extracellular matrix (ECM) in the tumor microenvironment (TME) and upregulated immune checkpoints (ICs) on antitumor immune cells impede the infiltration and killing effect of T cells, creating an immunosuppressive TME. Herein, a cholesterol oxidase (CHO) and lysyl oxidase inhibitor (LOX-IN-3) co-delivery copper-dibenzo-[g,p]chrysene-2,3,6,7,10,11,14,15-octaol single-site nanozyme (Cu-DBCO/CL) was developed. The conjugated organic ligand and well-distributed Cu-O4 sites endow Cu-DBCO with unique redox capabilities, enabling it to catalyze O2 and H2O2 to ·O2- and ·OH. This surge of reactive oxygen species (ROS) leads to impaired mitochondrial function and insufficient ATP supply, impacting the function of copper-transporting ATPase-1 and causing dihydrolipoamide S-acetyltransferase oligomerization-mediated cuproptosis. Moreover, multiple ROS storms and glutathione peroxidase 4 depletion also induce lipid peroxidation and trigger ferroptosis. Simultaneously, the ROS-triggered release of LOX-IN-3 reshapes the ECM by inhibiting lysyl oxidase activity and further enhances the infiltration of cytotoxic T lymphocytes (CD8+ T cells). CHO-triggered cholesterol depletion not only increases ·OH generation but also downregulates the expression of ICs such as PD-1 and TIM-3, restoring the antitumor activity of tumor-infiltrating CD8+ T cells. Therefore, Cu-DBCO/CL exhibits efficient properties in activating a potent antitumor immune response by cascade-enhanced CD8+ T cell viability. More importantly, ECM remodeling and cholesterol depletion could suppress the metastasis and proliferation of the tumor cells. In short, this immune nanoremodeler can greatly enhance the infiltration and antitumor activity of T cells by enhancing tumor immunogenicity, remodeling ECM, and downregulating ICs, thus achieving effective inhibition of tumor growth and metastasis.

Peroxisome-based metabolic engineering for biomanufacturing and agriculture.

Subcellular compartmentalization of metabolic pathways plays a crucial role in metabolic engineering. The peroxisome has emerged as a highly valuable and promising compartment for organelle engineering, particularly in the fields of biological manufacturing and agriculture. In this review, we summarize the remarkable achievements in peroxisome engineering in yeast, the industrially popular biomanufacturing chassis host, to produce various biocompounds. We also review progress in plant peroxisome engineering, a field that has already exhibited high potential in both biomanufacturing and agriculture. Moreover, we outline various experimentally validated strategies to improve the efficiency of engineered pathways in peroxisomes, as well as prospects of peroxisome engineering.

Strengthening the Metal-Acid Interactions by Using CeO2 as Regulators of Precisely Placing Pt Species in ZSM-5 for Furfural Hydrogenation.

Understanding the synergism between the metal site and acid site is of great significance in boosting the efficiency of bi-functional catalysts in many heterogeneous reactions, particularly in biomass upgrading. Herein, a "confined auto-redox" strategy is reported to fix CeO2-anchored Pt atoms on the inner wall of a ZSM-5 cage, achieving the target of finely controlling the placements of the two active sites. Compared with the conventional surface-supported counterpart, the encapsulated Pt/CeO2@ZSM-5 catalyst possesses remarkably-improved activity and selectivity, which can convert >99% furfural into cyclopentanone with 97.2% selectivity in 6 h at 160 °C. Besides the excellent catalytic performance, the ordered metal-acid distribution also makes such kind of catalyst an ideal research subject for metal-acid interactions. The following mechanization investigation reveals that the enhancement is strongly related to the unique encapsulation structure, which promotes the migration of the reactants over different active sites, thereby contributing to the tandem reaction.

Programmed Targeting Pyruvate Metabolism Therapy Amplified Single-Atom Nanozyme-Activated Pyroptosis for Immunotherapy.

Increasing cellular immunogenicity and reshaping the immune tumor microenvironment (TME) are crucial for antitumor immunotherapy. Herein, this work develops a novel single-atom nanozyme pyroptosis initiator: UK5099 and pyruvate oxidase (POx)-co-loaded Cu-NS single-atom nanozyme (Cu-NS@UK@POx), that not only trigger pyroptosis through cascade biocatalysis to boost the immunogenicity of tumor cells, but also remodel the immunosuppressive TME by targeting pyruvate metabolism. By replacing N with weakly electronegative S, the original spatial symmetry of the Cu-N4 electron distribution is changed and the enzyme-catalyzed process is effectively regulated. Compared to spatially symmetric Cu-N4 single-atom nanozymes (Cu-N4 SA), the S-doped spatially asymmetric single-atom nanozymes (Cu-NS SA) exhibit stronger oxidase activities, including peroxidase (POD), nicotinamide adenine dinucleotide (NADH) oxidase (NOx), L-cysteine oxidase (LCO), and glutathione oxidase (GSHOx), which can cause enough reactive oxygen species (ROS) storms to trigger pyroptosis. Moreover, the synergistic effect of Cu-NS SA, UK5099, and POx can target pyruvate metabolism, which not only improves the immune TME but also increases the degree of pyroptosis. This study provides a two-pronged treatment strategy that can significantly activate antitumor immunotherapy effects via ROS storms, NADH/glutathione/L-cysteine consumption, pyruvate oxidation, and lactic acid (LA)/ATP depletion, triggering pyroptosis and regulating metabolism. This work provides a broad vision for expanding antitumor immunotherapy.

Polyethylene Upgrading to Liquid Fuels Boosted by Atomic Ce Promoters.

Hydrocracking catalysis is a key route to plastic waste upgrading, but the acid site-driven C-C cleavage step is relatively sluggish in conventional bifunctional catalysts, dramatically effecting the overall efficiency. We demonstrate here a facile and efficient way to boost the reactivity of acid sites by introducing Ce promoters into Pt/HY catalysts, thus achieving a better metal-acid balance. Remarkably, 100 % of low-density polyethylene (LDPE) can be converted with 80.9 % selectivity of liquid fuels over the obtained Pt/5Ce-HY catalysts at 300 °C in 2 h. For comparison, Pt/HY only gives 38.8 % of LDPE conversion with 21.3 % selectivity of liquid fuels. Through multiple experimental studies on the structure-performance relationship, the Ce species occupied in the supercage are identified as the actual active sites, which possess remarkably-improved adsorption capability towards short-chain intermediates.

Boosting the catalytic performance of Al2O3-supported Pd catalysts by introducing CeO2 promoters.

Maintaining the stability of noble metals is the key to the long-term stability of supported catalysts. In response to the instability of noble metal species at high temperatures, we developed a synergistic strategy of dual oxide supports. By designing and constructing ceria components with small sizes, we have achieved unity in the ability of catalytic materials to supply oxygen and stabilize metal species. In this study, we prepared Al2O3-CeO2-Pd (AlCePd) catalysts containing trace amounts of Ce through the hydrolysis of cerium acetate, which achieved 100% CO conversion at 160 °C. More importantly, the activity remained at its initial 100% in the long-term durability testing, demonstrating the high stability of AlCePd. In contrast, the CO conversion of the CeO2-Pd (CePd) catalyst decreased from 100% to 54% within 3 h. Through comprehensive studies, we found that this excellent catalytic performance stems from the stabilizing effect of an alumina support and the possible reverse oxygen spillover effect of small-sized ceria components, where small-sized ceria components provide active oxygen for independent Pd species, making it possible for the CO adsorbed on Pd to react with this oxygen species.

Boosting Electrochemical Nitrogen Fixation via Regulating Surface Electronic Structure by CeO2 Hybridization.

Electrocatalytic nitrogen reduction reaction (NRR) paves a sustainable way to produce NH3 but suffering from the relatively low NH3 yield and poor selectivity. High-performance NRR catalysts and a deep insight into the structure-performance relationship are higher desired. Herein, a molten-salt approach is developed to synthesize tiny CeO2 nanoparticles anchored by ultra-thin MoN nanosheets as advanced catalysts for NRR. Specifically, a considerably high NH3 yield rate of 27.5 µg h-1  mg-1 with 17.2% Faradaic efficiency (FE) can be achieved at -0.3 V vs (RHE) under ambient conditions. Experimental and density functional theory (DFT) calculations further point out that the incorporation of MoN with CeO2 can promotes the enlargement of the electron deficient area of nitrogen vacancy site. The enlarged electron deficient area contributes to the accommodation of lone pair electrons of N2 , which dramatically improves the N2 adsorption/activation and the key intermediates (*NNH and *NH3 ) generation, thus boosting the NRR performance.

Multi-Enzyme Co-Expressed Nanomedicine for Anti-Metastasis Tumor Therapy by Up-Regulating Cellular Oxidative Stress and Depleting Cholesterol.

Tumor cells movement and migration are inseparable from the integrity of lipid rafts and the formation of lamellipodia, and lipid rafts are also a prerequisite for the formation of lamellipodia. Therefore, destroying the lipid rafts is an effective strategy to inhibit tumor metastasis. Herein, a multi-enzyme co-expressed nanomedicine: cholesterol oxidase (CHO) loaded Co─PN3 single-atom nanozyme (Co─PN3 SA/CHO) that can up-regulate cellular oxidative stress, disrupt the integrity of lipid rafts, and inhibit lamellipodia formation to induce anti-metastasis tumor therapy, is developed. In this process, Co─PN3 SA can catalyze oxygen (O2 ) and hydrogen peroxide (H2 O2 ) to generate reactive oxygen species (ROS) via oxidase-like and Fenton-like properties. The doping of P atoms optimizes the adsorption process of the intermediate at the active site and enhances the ROS generation properties of nanomedicine. Meantime, O2 produced by catalase-like catalysis can combine with excess cholesterol to generate more H2 O2 under CHO catalysis, achieving enhanced oxidative damage to tumor cells. Most importantly, cholesterol depletion in tumor cells also disrupts the integrity of lipid rafts and inhibits the formation of lamellipodia, greatly inhibiting the proliferation and metastasis of tumor cells. This strategy by up-regulating cellular oxidative stress and depleting cellular cholesterol constructs a new idea for anti-metastasis-oriented cancer therapy strategies.

Multiple Energy Transfer Channels in Rare Earth Doped Multi-Exciton Emissive Perovskites.

Revealing the energy transfer (ET) process from excitons to rare earth ions in halide perovskites has great guiding value for designing optoelectronic materials. Here, the multiple ET channels in multi-exciton emissive Sb3+ /Nd3+ co-doped Cs2 ZrCl6 are explored to comprehend the ET processes. Förster-Dexter ET theory reveals that the sensitizer concentration rather than the overlap integral of the spectra plays the leading function in the comparison of the ET efficiency among multiple ET channels from the host self-trapped excitons (STEs) and dopant triplet STEs to Nd3+ ions. Besides, Sb3+ /Nd3+ co-doped Cs2 ZrCl6 enables varied color delivery and has great potential as anti-counterfeiting material. Under X-ray irradiation, Sb3+ /Nd3+ co-doped Cs2 ZrCl6 presents a high light yield of ≈13300 photons MeV-1 and promising X-ray imaging ability. This work provides new insight for investigating the ET efficiency among multiple ET processes and presents great potentiality of multi-exciton emissive perovskites in the fields of anti-counterfeiting and X-ray imaging.

Pathogen-Activated Macrophage Membrane Encapsulated CeO2 -TCPP Nanozyme with Targeted and Photo-Enhanced Antibacterial Therapy.

Nanozymes with peroxidase-mimic activity have recently emerged as effective strategies for eliminating infections. However, challenges in enhancing catalytic activities and the ability to target bacteria have hindered the broader application of nanozymes in bacterial infections. Herein, a novel nanozyme based on mesoporous CeO2 nanosphere and meso-tetra(4-carboxyphenyl)porphine (TCPP) encapsulated within pathogen-activated macrophage membranes, demonstrates photodynamic capability coupled with photo-enhanced chemodynamic therapy for selective and efficient antibacterial application against infected wounds. Interestingly, the expression of Toll-like receptors accordingly upregulates when macrophages are co-cultured with specific bacteria, thereby facilitating to recognition of the pathogen-associated molecular patterns originating from bacteria. The CeO2 not only serve as carriers for TCPP, but also exhibit intrinsic peroxidase-like catalytic activity. Consequently, Staphylococcus aureus (S. aureus)-activated macrophage membrane-coated CeO2 -TCPP (S-MM@CeO2 -TCPP) generated singlet oxygen, and simultaneously promoted photo-enhanced chemodynamic therapy, significantly boosting reactive oxygen species (ROS) to effectively eliminate bacteria. S-MM@CeO2 -TCPP specifically targeted S. aureus via Toll-like receptor, thereby directly disrupting bacterial structural integrity to eradicate S. aureus in vitro and relieve bacteria-induced inflammation to accelerate infected wound healing in vivo. By selectively targeting specific bacteria and effectively killing pathogens, such strategy provides a more efficient and reliable alternative for precise elimination of pathogens and inflammation alleviation in microorganism-infected wounds.

Formamide Electrosynthesis from Methanol and Ammonia in Water over Pr-Doped MnO2.

A rare earth element doping strategy is reported to boost the activity and enhance the stability of MnO2 for selective formamide production through electrocatalytic oxidation coupling (EOC) of methanol and ammonia. MnO2 doped with 1% Pr was selected as the best candidate with an optimized formamide yield of 211.32 µmol cm-2 h-1, a Faradaic efficiency of 22.63%, and a stability of more than 50 h. The easier formation of Mn6+ species and the lower dissolution rate of Mn species over Pr-doped MnO2 revealed by in situ Raman spectra were responsible for the boosted formamide production and enhanced stability. In addition, a two-electrode flow electrolyzer was developed to integrate EOC with C2H2 semihydrogenation for simultaneously producing value-added products in both the anode and cathode.

Increased TCP11 gene expression can inhibit the proliferation, migration and promote apoptosis of cervical cancer cells.

BACKGROUND: Cervical cancer is a common gynecological malignancy. Gene microarray found that TCP11 gene was highly expressed in cervical cancer. However, the effect of TCP11 gene on the proliferation, apoptosis and migration of cervical cancer cells and its underlying molecular mechanisms are unclear. METHODS: GEPIA database, tissue microarray, western blot and qRT-PCR were used to analyze the expression of TCP11 gene in cervical cancer tissues and cells and its relationship with patients' survival rate. The cell cycle and apoptosis were detected by flow cytometry, and the expressions of cell cycle and apoptosis related molecules and EMT-related molecules were detected by Western blot and qRT-PCR. RESULTS: The results showed that TCP11 gene was highly expressed in cervical cancer tissues and cells compared with normal cervical tissues and cells, and its expression was positively correlated with patients' survival rate. The results of proliferation and migration assays showed that TCP11 overexpression inhibited the proliferation and migration of HeLa and SiHa cells. The results showed that TCP11 overexpression blocked the cell cycle of HeLa and SiHa cells, decreased the expression of CDK1 and Cyclin B1, and increased the apoptosis and the expression of caspase-3, cleaved-caspase-3 and cleaved-PARP. TCP11 overexpression increased the protein and mRNA expression of EMT-related molecules ZO-1 and E-cadherin. Conversely, TCP11 knockdown promoted the proliferation of HeLa and SiHa cells and the migration of HeLa cells. CONCLUSIONS: TCP11 overexpression significantly inhibited the occurrence and development of cervical cancer cells, it may be a potentially beneficial biomarker for cervical cancer.

A Cholesterol Metabolic Regulated Hydrogen-Bonded Organic Framework (HOF)-Based Biotuner for Antibody Non-Dependent Immunotherapy Tailored for Glioblastoma.

The metabolic reprogramming of glioblastoma (GBM) poses a tremendous obstacle to effective immunotherapy due to its impact on the immunosuppressive microenvironment. In this work, a hydrogen-bonded organic framework (HOF) specifically designed for GBM immunotherapy is developed, taking advantage of the relatively isolated cholesterol metabolism microenvironment in the central nervous system (CNS). The HOF-based biotuner regulates extra/intracellular cholesterol metabolism, effectively blocking the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway and reducing 2B4 expression. This metabolically disrupts the immunosuppressive microenvironment of GBM and rejuvenates CD8+ T cells. Moreover, cholesterol metabolism regulation offers additional benefits in treating GBM invasion. Furthermore, tumor microenvironment (TME)-initiated chemiexcited photodynamic therapy (PDT) is enhanced during the regulation of cholesterol metabolism, and the biotuner can effectively trigger immunogenic cell death (ICD) and increase the infiltration of cytotoxic T lymphocytes (CTLs) in GBM. By reversing the immunosuppressive microenvironment and bolstering chemiexcited-PDT, this approach invigorates efficient antibody non-dependent immunotherapy for GBM. This study provides a model for enhancing immunotherapy through cholesterol metabolism regulation and explores the feasibility of a "metabolic checkpoint" strategy in GBM treatment.