Lipid nanoparticles (LNPs) are clinically established carriers for nucleic acid therapeutics and mRNA-based vaccines. Current LNP formulations often use poly(ethylene glycol) (PEG)-based surface modifications to enhance pharmacokinetics, colloidal stability, and shelf life. However, PEG moieties can elicit anti-PEG immune responses, reactogenicity, and hypersensitivity reactions. Here, we investigated heparosan (HEP), a naturally occurring, biodegradable polysaccharide, for mRNA-LNP surface engineering and mRNA delivery in vitro and in vivo. We synthesized a library of HEP-coated LNPs and systematically characterized their physicochemical properties, including nanoparticle size, polydispersity, ζ potential, and mRNA encapsulation efficiency. We evaluated the delivery performance using two different mRNA payloads in both cultured cells and mouse models. Using HEP-engineered mRNA-LNPs, we demonstrate efficacy comparable to that of PEG-modified counterparts, with minimal tissue damage and negligible immune activation. In summary, our results highlight HEP as an immunologically silent, biocompatible coating agent that enables the formulation of colloidally stable LNPs for safe and effective mRNA delivery in vitro and in vivo, offering a potential path toward next-generation PEG-free nanomedicines.

A FeCuO x bimetallic catalyst exhibits excellent NO 3 RR performance in neutral electrolyte, achieving high performance.

Most pancreatic ductal adenocarcinoma (PDAC) single-cell and spatial studies analyze one cohort or platform, obscuring recurrent biology. We assembled a human pancreas single-cell and single-nucleus reference of 1,186,130 cells from 19 studies and interpreted 176 Visium sections comprising 458,877 spots across non-diseased pancreas, chronic pancreatitis, PanIN, IPMN, primary PDAC and metastasis. Marker-supported labels were used after two RNA-based copy-number callers failed known-diploid controls. BANKSY domains, two reference-mapping methods and sample-level analyses resolved a cross-sectional epithelial axis extending from acinar-rich to malignant tissue. Five trajectory algorithms recovered similar ordering on a shared embedding; their consensus was interpreted as transformation-associated, not temporal or clonal. Malignant regions were globally segregated from fibroblast and myeloid compartments. Signed-distance analysis refined this pattern into a malignant core, a CAF/myeloid surround beginning at the tumour boundary and a more distal lymphoid compartment. Candidate extracellular-matrix communication, led by COLLAGEN, LAMININ and FN1, concentrated at the interface. Changes were reproduced in six patient-matched Normal-tumour pairs using exact patient-level tests. Visium HD resolved the same organization at single-cell resolution and showed that 8-um bins distorted immune-adjacency estimates. Xenium also revealed recurrent neighbourhoods but sample-specific stromal boundaries. We provide a confound-aware framework for identifying recurrent epithelial and microenvironmental organization in PDAC.

A two-step wet impregnation method was developed to synthesize a FeCuOx bimetallic catalyst featuring a Cu2O nanowire scaffold as a nanotemplate for anchoring Fe2O3 nanoparticles. The catalyst exhibits excellent NO3RR performance in neutral electrolyte, achieving a faradaic efficiency of 90.3% and an NH3 yield of 4609.6 µg cm-2 h-1, attributed to Cu-Fe interfacial electronic coupling that balances *NO3 activation on Fe2O3 with *NO2/*NHx hydrogenation and NH3 release on Cu2O, thereby promoting rapid intermediate transfer and suppressing side pathways.

Melanoma, a highly aggressive skin cancer, presents significant therapeutic challenges owing to its metastatic potential. Targeting deoxyhypusine synthase (DHPS), a pivotal enzyme in the activation of eukaryotic translation initiation factor 5A (eIF5A), emerges as a promising therapeutic strategy for melanoma. In this study, we designed and synthesized a series of 2-benzyl-5-(2-methoxybenzyl)-1,3,4-oxadiazole derivatives as novel allosteric DHPS inhibitors. Through molecular docking, dynamics simulations, scaffold screening, and comprehensive biological evaluations, we identified 7C16 as the most potent compound, demonstrating superior enzymatic inhibition (IC50 = 0.07 μM) and anti-proliferative activity against melanoma cells (IC50, A375 = 4.00 μM). Notably, 7C16 significantly suppressed melanoma cell migration and invasiveness in vitro and exhibited potent anti-tumor efficacy in an A375 cell zebrafish xenograft model. These findings highlight 7C16 as a promising candidate for developing targeted anti-melanoma therapies.

Localized ablative immunotherapy (LAIT), a combination of photothermal therapy (PTT) and the immunostimulant glycated chitosan (GC), has demonstrated therapeutic efficacy in cancer treatment. However, its impact on the tumor microenvironment (TME), particularly on tumor-infiltrating natural killer (TINK) cells, remains to be fully elucidated. Using single-cell RNA sequencing (scRNAseq), we analyzed the transcriptional and functional modulations of TINK cells by LAIT in a mouse breast cancer model. Additionally, we investigated immune checkpoint inhibitor (ICI)-induced changes in NK cells across multiple cancer types and evaluated the clinical relevance of these transcriptional changes using The Cancer Genome Atlas (TCGA) database. ScRNAseq revealed five NK cell subtypes, with LAIT increasing the proportion of interferon-enriched NK cells and enhancing NK cell differentiation and cytotoxicity. Functional analyses demonstrated that LAIT upregulated activation, cytotoxic, and interferon pathway genes while downregulating immune-suppressive genes, effects largely driven by GC. Comparative analysis showed significant transcriptional overlap between ICI and LAIT, highlighting shared pathways in NK cell-mediated cytotoxicity and chemokine signaling. Prognostic models constructed from ICI- and LAIT-induced gene signatures effectively stratified breast cancer patients by survival risk, with LAIT-induced genes showing the highest predictive performance. Furthermore, higher NK cell proportions and the expression of key prognostic genes, such as PSME2, IGKC, and KLRB1, were associated with improved overall survival. LAIT and ICIs enhance NK cell-mediated antitumor responses via distinct yet complementary mechanisms, emphasizing their potential for synergistic use. These findings provide novel insights into NK cell modulation within the TME and support the development of combinatorial immunotherapy strategies.

Photocatalytic α-C-H activation of alcohols to form aldehydes and ketones represents an important synthetic pathway, although the selective formation of C-centered radicals remains challenging due to competing O-H activation processes. While extensive research has explored heterojunction band alignment, charge transfer directionality, and component-specific redox reactions, the atomic structure at interfaces and its catalytic role have received limited attention. Here, we demonstrate a TiO2-CuO heterojunction photocatalyst that achieves exceptional selectivity in the oxidation of isopropanol to acetone, with a hydrogen production rate of approximately 4400 μmol/g/h. Through complementary characterization using X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR), and ab initio molecular dynamics (AIMD), we identify the formation of asymmetric Ti-O(H)-Cu+ units at the TiO2/CuO heterojunction interface. In situ EPR reveals a ·C(OH)(CH3)2 radical intermediate, confirming that the reaction proceeds via selective hydrogen atom transfer (HAT) of the α-C-H bond in isopropanol, in contrast to that of TiO2 or CuO, which proceed via hydrogen extraction of the OH group. These mechanistic insights into interface-mediated catalysis provide new design principles for engineering atomic-scale catalytic interfaces, offering new opportunities for developing next-generation photocatalysts across diverse catalytic applications.

Converting CO2 into methane using solar energy, which requires the continuous transfer of eight electrons, presents significant challenges in achieving both high selectivity and a high yield. In this study, we introduce a plasmonic modulation strategy of surface vacancies to enhance the methanation of CO2 in pure water. Using Ag-TiO2 core-shell nanoparticles (NPs) as a model system, we demonstrate that the plasmonic electric field generated by light-excited silver cores permeates the TiO2 shell, globally modulating the reactivity and selectivity of surface vacancies at every site without exception. This achieves fully selective conversion of CO2 to CH4 with a notable efficiency among existing methanation systems. Additionally, the spontaneous interlinking of NPs enhances the local electric field at particle-particle interfaces through cumulative localized surface plasmon resonance, leading to further improvements in activity and selectivity. This cumulative plasmonic enhancement exponentially increases the electric field strength, thereby boosting the photocatalytic performance. Our plasmon-enhanced design underscores the potential of spatially transferring the plasmonic microenvironment toward the outer surface, offering a general strategy to enhance photoactivity and selectivity in photocatalysts.

To address global challenges in sustainable energy and water treatment, metamaterials have emerged as a transformative class of materials for solar-driven photocatalysis. Through nanoscale engineering, these artificially structured materials enable precise manipulation of light-matter interactions and significantly enhance solar energy utilization beyond the limits of conventional photocatalysts. This review systematically summarizes recent progress in applying metamaterials to solar-driven processes for energy conversion and water treatment, including photocatalytic CO2 reduction, water splitting for hydrogen generation, degradation of organic pollutants, and solar-driven water evaporation for purification. Key enhancement mechanisms include localized surface plasmon resonance, photonic bandgap engineering, and improved charge separation via metamaterial and semiconductor heterojunctions, which collectively improve light absorption, charge separation and transfer, and surface reactivity. Practical challenges related to scalable fabrication, long-term durability, and integration into real-world systems are also examined. Finally, emerging directions, including AI-assisted inverse design, structural chirality, and multifunctional hybrid architectures, are discussed as promising strategies to further advance metamaterial-based photocatalysts in sustainable energy and environmental applications.

One effective strategy for mitigating carbon emissions is utilizing carbon dioxide as a substrate to synthesize high-value multi-carbon products through the electrochemical CO2 reduction reaction (CO2RR). Despite the widespread application of C3+ oxygenated hydrocarbons, including propanol, acetone, and butanol, in numerous industrial chemical processes, the literature provides scant reporting on their role in electrochemical CO2 reduction reactions. In this review, the reaction mechanisms specific to predominant C3 products are analyzed in detail. Subsequently, we outline advancements concerning three distinct variants of Cu-based catalysts, namely 1) Cu oxide-derived catalysts, 2) Cu nanoparticle catalysts, and 3) Cu single atoms and molecular Cu catalysts. Meanwhile, the feasibility of designing copper-based tandem catalytic systems to produce C3+ products in CO₂RR is also discussed. Additionally, the review explores the emergence of non-Cu-based catalysts, particularly nickel (Ni)- and molybdenum (Mo)-based transition-metal phosphides and chalcogenides. These systems, with the characterization of high catalytic efficiency, excellent stability and low cost, provide sustainable and economical alternatives. The integration of such catalysis offers promising solutions to overcome existing limitations, paving the way for efficient, scalable, and sustainable CO2RR technologies. Besides artificial intelligence (AI) and machine learning (ML) combined with DFT and high-throughput (HT) experiments, as a new paradigm shift in data-driven catalyst exploration, this review addressed some promising recent work for catalysts to yield C3+ products from CO2RR on that edge.

Iron oxides are notable among oxide semiconductors for their abundance and environmental friendliness, positioning Fe2O3 as a promising candidate for industrial nanotechnology. However, polymorphic Fe2O3 presents up to four phases, posing significant challenges in customizing them for nanocatalysis, including tasking a single phase with complex catalytic reactions, harnessing synergistic advantages during phase integration, and achieving selective reactivity amidst competing side reactions. Here, we developed a 2D-templated Z-direction-confining strategy combined with dual-phase nanocrystallization to synthesize thin-layered Fe2O3 with an in-plane nanoscale integration of α- and γ-phases. The resulting dual-phase Fe2O3 achieved superior electrochemical nitrate reduction to ammonia, yielding 4329.8 μg/mgcat/h at -0.8 V vs a reversible hydrogen electrode with high faradaic efficiency (∼95.7%) and outstanding selectivity (99.9%). Combined computational and experimental studies revealed that the enhanced performance arises from the synergistic integration of electron transport through the γ phase and active sites within the α phase, facilitated by ultrafine nanophase domains. Electrons reaching the α phase selectively drive nitrate reduction over proton reduction. The electrocatalyst exhibited exceptional stability across 28 cycles. This catalyst, with its high yield, faradaic efficiency, selectivity, stability, and low cost, outperforms previous catalysts under comparable conditions, highlighting the potential of nanophase manipulation for sustainable ammonia electrosynthesis from nitrate waste.

Discovering new treatments for melanoma will benefit human health. The mechanism by which deoxyhypusine synthase (DHPS) promotes melanoma development remains elucidated. Multi-omics studies have revealed that DHPS regulates m6A modification and maintains mRNA stability in melanoma cells. Mechanistically, DHPS activates the hypusination of eukaryotic translation initiation factor 5A (eIF5A) to assist METTL3 localizing on its mRNA for m6A modification, then promoting METTL3 expression. Structure-based design, synthesis, and activity screening yielded the hit compound GL-1 as a DHPS inhibitor. Notably, GL-1 directly inhibits DHPS binding to eIF5A, whereas GC-7 cannot. Based on the clarification of the mode of action of GL-1 on DHPS, it is found that GL-1 can promote the accumulation of intracellular Cu2+ to induce apoptosis, and antibody microarray analysis shows that GL-1 inhibits the expression of several cytokines. GL-1 shows promising antitumor activity with good bioavailability in a xenograft tumor model. These findings clarify the molecular mechanisms by which DHPS regulates melanoma proliferation and demonstrate the potential of GL-1 for clinical melanoma therapy.

Investigating myeloid cells' role during cancer therapy is critical to developing novel strategies, as they shape the tumor microenvironment and modulate anti-tumor immune responses. Using single-cell RNA sequencing (scRNAseq), we examined the impact of the immunostimulant N-dihydrogalactochitosan (GC) on myeloid cells within MMTV-PyMT tumors. We discovered unique myeloid cell clusters with varied responses to GC, showing increased proportions of certain cell types, such as G-MDSC, monocytes, and DCs. Importantly, we observed significant upregulation of STING signaling-associated genes, indicative of conventional STING signaling and canonical NFkB signaling activation. Furthermore, our analysis showed an upregulation of proinflammatory cytokines in cDCs, and a significant reduction in M2-like macrophages post-GC treatment. This supports GC's potent immunostimulatory properties, activating key cells within the tumor microenvironment to enhance antitumor immunity.

With freshwater resources becoming increasingly scarce, the photocatalytic seawater splitting for hydrogen production has garnered widespread attention. In this study, a novel photocatalyst consisting of a Cu core coated is introduced with N-doped C and decorated with single Co atoms (Co-NC@Cu) for solar to hydrogen production from seawater. This catalyst, without using noble metals or sacrificial agents, demonstrates superior hydrogen production effficiency of 9080 µmolg-1h-1, i.e., 4.78% solar-to-hydrogen conversion efficiency, and exceptional long-term stability, operating over 340 h continuously. The superior performance is attributed to several key factors. First, the focus-light induced photothermal effect enhances redox reaction capabilities, while the salt-ions enabled charge polarization around catalyst surfaces extends charge carrier lifetime. Furthermore, the Co─NC@Cu exhibits excellent broad light absorption, promoting photoexcited charge production. Theoretical calculations reveal that Co─NC acts as the active site, showing low energy barriers for reduction reactions. Additionally, the formation of a strong surface electric field from the localized surface plasmon resonance (LSPR) of Cu nanoparticles further reduces energy barriers for redox reactions, improving seawater splitting activity. This work provides valuable insights into intergrating the reaction environment, broad solar absorption, LSPR, and active single atoms into a core-shell photocatalyst design for efficient and robust solar-driven seawater splitting.

Mucosal vaccinations for respiratory pathogens provide effective protection as they stimulate localized cellular and humoral immunities at the site of infection. Currently, the major limitation of intranasal vaccination is using effective adjuvants capable of withstanding the harsh environment imposed by the mucosa. Herein, we describe the efficacy of using a unique biopolymer, N-dihydrogalactochitosan (GC), as a nasal mucosal vaccine adjuvant against respiratory infections. Specifically, we mixed GC with recombinant SARS-CoV-2 trimeric spike (S) and nucleocapsid (NC) proteins to intranasally vaccinate K18-hACE2 transgenic mice, in comparison with Addavax (AV), an MF-59 equivalent. In contrast to AV, intranasal application of GC induces a robust, systemic antigen -specific antibody response and increases the number of T cells in the cervical lymph nodes. Moreover, GC + S + NC -vaccinated animals were largely resistant to the lethal SARS-CoV-2 challenge and experienced drastically reduced morbidity and mortality, with animal weights and behavior returning to normal 22 days post -infection. In contrast, animals intranasally vaccinated with AV + S + NC experienced severe weight loss, mortality, and respiratory distress, with none surviving beyond 6 days post -infection. Our findings demonstrate that GC can serve as a potent mucosal vaccine adjuvant against SARS-CoV-2 and potentially other respiratory viruses. Statement of significance We demonstrated that a unique biopolymer, N-dihydrogalactochitosan (GC), was an effective nasal mucosal vaccine adjuvant against respiratory infections. Specifically, we mixed GC with recombinant SARSCoV-2 trimeric spike (S) and nucleocapsid (NC) proteins to intranasally vaccinate K18-hACE2 transgenic mice, in comparison with Addavax (AV). In contrast to AV, GC induces a robust, systemic antigen -specific antibody response and increases the number of T cells in the cervical lymph nodes. About 90 % of the GC + S + NC -vaccinated animals survived the lethal SARS-CoV-2 challenge and remained healthy 22 days post -infection, while the AV + S + NC -vaccinated animals experienced severe weight loss and respiratory distress, and all died within 6 days post -infection. Our findings demonstrate that GC is a potent mucosal vaccine adjuvant against SARS-CoV-2 and potentially other respiratory viruses. (c) 2024 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY -NC -ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )