Ulcerative colitis (UC) has long defied safe and curative treatment. Opuntia Milpa Alta-derived exosome-like vesicles (ODV) have been isolated with lipid-wrapped messengers, and loaded with anti-inflammatory phenols, lipids, and proteins. When given orally to mice with DSS-induced colitis, these plant-derived vesicles (PDV) ignored healthy tissue but homed to inflamed colon, where they quietly rebuilt the broken barrier. Colon length was restored, weight loss halted, goblet cells returned, and pro-inflammatory storms (TNF-α, IL-6, and IL-1β) were silenced as effectively as the standard drug 5-ASA–yet without toxicity. ODV reshaped the chaotic gut microbiota, reviving SCFAs-producing heroes (Lactobacillus, Akkermansia, and Muribaculaceae) while banishing pathogens; three absorbed phenolic phytochemicals (piscidic acid, eucomic acid, and p-hydroxybenzoic acid) then reprogrammed colonic fatty acid metabolism via key genes (Acsl1, Acaca, and Fabp4a), turning inflammation off at its metabolic roots. Thus, ODV offers a safe, natural, and mechanistically innovative path forward for colitis and beyond.
Alcoholic liver disease (ALD) has emerged as a critical global health concern. Dendrobium officinale polysaccharide (DOP) shows therapeutic potential against ALD. However, despite its promising effects, the protective mechanism of DOP on the ALD is unclear. To investigate the protective mechanisms of DOP, we successfully established an ethanol-induced liver injury model in mice and treated ALD mice with DOP. The results demonstrate that DOP treatment significantly reduced hepatic TG, TC, AST, ALT and MDA levels, while enhancing antioxidant capacity through elevated SOD, GST and GPx, reduced GSH and CAT activities. Mechanistically, DOP activates the KEAP1-Nrf2 signalling pathway, reduces the expression of Keap1, and simultaneously upregulates the expression of Nrf2 and its downstream target NQO1. Furthermore, DOP restored lipid homeostasis in ALD mice. In summary, these findings provide strong scientific evidence for the therapeutic potential of DOP in the treatment of ALD and establish a foundation for developing DOP based natural hepatoprotective agents.
Artificial intelligence (AI) has accelerated materials discovery, yet its translation to industrial manufacturing remains limited due to two critical gaps: the scarcity of proprietary industrial datasets and the absence of application-oriented benchmarks. To address these challenges, we develop the AP-Lab, an AI-Driven Autonomous Pilot-Scale Laboratory workstation designed to bridge research and manufacturing. Using magnetic nanoparticles (MNPs) for viral nucleic acids (NAs) extraction as a case study, the AP-Lab integrates four agent-controlled systems for user interaction, optimization scheme generation, autonomous synthesis and testing, and data management. By leveraging localized industrial datasets and adopting Polymerase Chain Reaction (PCR) cycle threshold (Ct) values as an application-specific benchmark, the AP-Lab achieves rapid optimization of MNPs-based NAs extraction products at pilot-scale corresponding to 50,000 tests per batch within three weeks, and enables scale-up manufacturing of 1 million tests per batch in two months. Compared to conventional manual workflows, the AP-Lab reduces development timelines from four to six months to three weeks while delivering performance superior to leading commercial products. This work demonstrates a scalable strategy for AI-driven pilot-scale production and offers a blueprint for accelerating industrial adoption of advanced materials.
The stability and activity of self-cascade enzymes based on glucose oxidase (GOx) and peroxidase (POD) are usually low, which has significant limitations in tumor catalytic therapy. Building nanoislands-supported single-atom nanozymes with strong atomic-nano interaction is an effective strategy for enhancing the self-cascade enzyme-like activity. Herein, noble metal iridium (Ir) single-atoms are successfully deposited on CeO2 quantum dots (QDs) nanoislands to construct Ir/CeO2 single-atom nanoislands (SANIs). The CeO2 QDs nanoislands with abundant oxygen vacancies facilitate efficient electron transfer of Ir single-atoms at the metal-nanoislands interface. A liposomal nano platform encapsulated with Ir/CeO2 SANIs (Ir/CeO2@Lipo) is further developed for in vivo catalytic therapy. The Ir/CeO2@Lipo exhibits excellent self-cascade GOx- and POD-like activity due to its unique atomic-nano structures and the confined effect of the nanoislands. Compared with CeO2@Lipo and other reported nanozymes, Ir/CeO2@Lipo catalyzes glucose to generate more ROS with higher efficiency, demonstrating superior GOx-POD self-cascade enzyme-like activity. In vivo, experiments demonstrate that Ir/CeO2@Lipo possesses excellent tumor-targeting capability as well as nearly complete tumor ablation through ROS-mediated apoptotic pathways. Thus, this work provides a new paradigm for designing self-cascade enzymes for tumor treatment strategies.
A purely organic supramolecular assembly emitting room-temperature phosphorescence (RTP) was constructed from 1-(3-(bis(pyridin-2-ylmethyl)amino)propyl)-4-(4-bromophenyl)pyridin-1-ium bromide (BP-DPA) by complexing with cucurbit[8]uril (Q[8]) and Zn2+ through a supramolecular assembly. Benefiting from the strong affinity and the macrocyclic restriction effect of Q[8], phosphorescence emission was achieved by encapsulating BP-DPA in the Q[8] cavity. Notably, secondary assembly with Zn2+ formed the supramolecular complex BP-DPA@Q[8]⊂Zn2+, which greatly contributed to the enhancement of the phosphorescence quantum yield and lifetime from 1.75% to 6.25% and from 0.48 to 1.25 ms, respectively. Meanwhile, BP-DPA@Q[8] specifically recognizes Zn2+ with a low detection limit without interference from common metal ions, anions, and biomolecules. It permeates the plasma membrane of cells and emits a specific phosphorescence response signal in the presence of Zn2+. In addition, this material can also be utilized for the development of portable indicator papers, enabling the rapid and visualized detection of Zn2+. This work provides a route for constructing multilevel supramolecular assemblies of RTP, extending the biological applications of purely organic RTP materials and offering additional possibilities for the potential utilization of cucurbit[n]uril-based room-temperature phosphorescence materials.
The aim of this study was to design and synthesize 17 novel 1,2,4-triazole thioether derivatives containing 1,3,4-thiadiazole thioether.
Single‐atom nanozymes (SANs) encounter significant challenges in achieving optimal activity due to the insufficient synergistic modulation of isolated catalytic sites. Herein, a photochemical reduction strategy is presented for simultaneously constructing Pt‐O 6 catalytic centers and oxygen vacancies (OVs) within mesoporous silica‐supported platinum single‐atoms (mSiO 2 ‐PtSANs). The density of OVs can be dynamically regulated by adjusting the UV exposure time. This UV‐mediated dynamic engineering of OVs significantly enhances the oxidase (OXD)‐like activity of mSiO 2 ‐PtSANs, leading to a 34.3‐fold reduction in the Michaelis–Menten constant ( K m ) value and a 62.8‐fold increase in catalytic efficiency ( K cat / K m ). Density functional theory (DFT) calculations demonstrate that OVs promote O 2 activation, facilitate electron transfer, and reduce the energy barrier for ·OH formation. Engineered with abundant OVs, the mSiO 2 ‐PtSANs drive persistent reactive oxygen species (ROS) generation, which can act as an effective strategy to amplify ferroptotic cell death. To further harness this therapeutic synergy, the ferroptosis inducer RSL3 is loaded into the nanoplatform with a drug loading efficiency of 65.8%, yielding the mSiO 2 ‐PtSANs@RSL3 nanocatalytic agent. This integrated system significantly enhances antitumor efficacy through the synergistic combination of chemodynamic therapy (CDT) and ferroptosis induction, as demonstrated in both in vitro and in vivo models. The study establishes a novel paradigm for the atomically precise design of SANs through OVs‐mediated electronic modulation.
Achieving high metal loadings in metal-organic frameworks (MOFs)-based single-atom catalysts (SACs) remains a major challenge due to the degradation of anchoring sites during high-temperature synthesis. Here, a low-temperature photochemical reduction strategy that preserves the structural integrity of MOF and maximizes the density of unsaturated pyridinic nitrogen sites for efficient metal atom anchoring is reported. This pyrolysis-free approach enables the synthesis of SACs with record-high metal loadings, up to 20.5 wt.% for Pt, 16.9 wt.% for Ru, 15.4 wt.% for Os, 12.9 wt.% for Fe, and 9.6 wt.% for Cu, surpassing previous MOF-derived SACs by one order of magnitude. Density functional theory (DFT) calculations reveal that the unique Pt-N2Cl2 coordination significantly enhances oxidase-like activity compared to conventional Pt-N3 configurations. Furthermore, the high metal loading increases the density of catalytically active sites, thereby improving overall catalytic efficiency. As a proof of concept, a Pt-SACs@MOF-based immunosensor achieves ultrasensitive detection of α-fetoprotein (AFP) with a detection limit as low as 3 fg mL-1. This work offers a general and scalable strategy for synthesizing high-density SACs, addressing the long-standing trade-off between metal loading and structural stability in MOF-based catalysts.
Overexpression of EphB3 has been documented across various cancers and essential for cell proliferation, survive and metastasis, making it a valuable therapeutic target. In this study, a series of novel penta-1,4-dien-3-one and quinoxaline conjugates were designed and synthesized using pharmacophore fusion strategies to explore potential EphB3 inhibitors. CCK-8 experiments revealed significant anti-cancer activity of most newly synthesized compounds against hepatocellular carcinoma (HCC). Among them, compound W8 displaying the highest inhibitory activity against MHCC97H (IC50 = 1.87 μM), which arrests MHCC97H cells in the G0/G1 phase and induces apoptosis. Furthermore, compound W8 suppresses tumor growth in an MHCC97H xenograft model in vivo by suppressing phosphorylation level of EphB3 and down-regulating the SRC-AKT signaling pathway, leading to a dose-dependent reduction in tumor volumes and weights, with a 40 mg/kg dose achieving decreases of 68.4 % and 65.3 %, respectively. Given its ability to modulate EphB3 signaling, W8 represents a promising lead compound for further drug development, particularly for cancers characterized by EphB3 overexpression, and may offer new opportunities for targeted therapy in precision oncology.
The construction of bimetallic catalysts with two catalytic sites is reported to be an innovative and effective approach to enhance catalytic activity. Accurate structural design is one of most important approaches in regulating the compatibility of the synergistic effects between the two catalysts of bimetallic nanozymes but remains an enormous challenge. In this study, the Cu@MnO bimetallic catalyst with a core-shell structure is designed and synthesized using Cu2O precursor as the sacrifice template. The bimetallic oxide Cu@MnO nanozyme exhibits excellent oxidase-mimicking activity to catalyze 3,3'5,5'-tetramethylbenzidine (TMB) within 1 min. Density functional theory calculations demonstrate that the enhanced absorption and activation of O2 near the bimetallic catalyst sites via the synergistic and augmenting effects between the Cu and Mn sites. Based on the efficient oxidase-like activity of the Cu@MnO nanozyme, we propose a colorimetric assay and exhibit the most excellent analytical performances reported so far in the colorimetric detection of uric acid (UA). The linear range is 0.1-1500 μM in solution buffer and 0.5-1000 μM in human blood serum, with the limit of detection of 0.036 μM and 0.16 μM, respectively. According to the Receiver Operating Characteristic (ROC) curve, the Cu@MnO nanozyme shows a high precision in quantifying real clinical blood samples with the sensitivity and specificity above 90 %. The proposed core-shell Cu@MnO bimetallic catalyst not only provides a simple method for UA detection but also sheds light on the construction of other nanozyme-based biosensing platforms.
Electrocatalysis is a powerful approach to accelerate sulfur redox kinetics in lithium-sulfur (Li-S) batteries. However, in practical high sulfur loading and thick cathodes, the severe concentration polarization induced by the rapid depletion of local lithium ions (Li+) greatly restricts catalysis and battery performance, representing an engineering challenge in a closed microelectrochemical reactor. Here, an electrolyte-dispersible Li+-reservoir catalyst is proposed to sustain the local Li+ concentration to ensure the continuous electrochemical reaction in the battery with an energy density of over 400 Wh kg-1. Such a catalyst is realized by anchoring single cobalt atoms onto uniformly dispersed carbon quantum dots (Co-CQD). The negatively charged CQD strongly attracts and enriches Li+ around the Co catalytic sites by robust electrostatic interactions, ensuring a continuous Li+ supply during the catalytic reactions. Moreover, Co-CQDs are homogeneously dispersed in the electrolyte and distributed in thick electrodes, promoting bulk-phase Li+ distribution and effectively eliminating concentration polarization. As a result, this strategy lowers the sulfur conversion activation energy in thick cathodes from 1.27 to 0.72 eV and enables the battery to maintain a high reversible capacity of 13.5 mAh cm-2 under a high sulfur loading of 13 mg cm-2, outperforming conventional catalysts under identical conditions. Moreover, an Ah-level pouch cell delivers a high energy density of 513 Wh kg-1, offering a scalable strategy to overcome ion transport bottlenecks in thick cathodes for practical Li-S batteries.
Ferroptosis therapy employs reactive oxygen species (ROS) generated via Fenton or Fenton-like reactions. However, the antioxidant system associated with the tumor microenvironment (TME) exhibits high levels of glutathione (GSH) that significantly restrict the therapeutic efficacy of ferroptosis. In this study, we propose a near-infrared (NIR)-responsive hollow mesoporous manganese dioxide (HM-MnO2) nanoprobe with multi-enzyme-like activity for enhanced ROS generation and GSH depletion that can efficiently promote ferroptosis. The ferroptosis inducer RSL3 is encapsulated within HM-MnO2 with a loading capacity of 67 %, while iron-doped dopamine (Fe-PDA) and cRGD tumor-targeting peptides are conjugated on the surface. The resultant MnO2R@FePDA-cRGD nanocomposite delivers a photothermal conversion efficiency of 39.1 % under 808 nm irradiation, which can effectively trigger structural degradation of the nanoplatform and the rapid release of RSL3. The photothermal effects significantly augment catalytic activity, enabling a multi-enzyme mimicking that includes peroxidase (POD), oxidase (OXD), GSH peroxidase (GPx), and NADH oxidase (NOx) functions, generating significant ROS radicals and an efficient depletion of intracellular GSH. These cascade reactions contribute to an optimal TME for inducing "explosive" ferroptosis with a synergistic inhibition of tumor growth in vitro and in vivo. The proposed strategy represents a potent approach to amplifying ferroptosis through the photothermal-driven rapid release of RSL3 and enhanced multi-enzyme mimetic activities with significant potential in nanomedicine-based cancer therapy.
Berberine represents a prominent compound with commendable antitumor activity, a novel berberine derivative with substituted o-diaminobenzene moiety linked at the 9-position through oxadiazole and alkyl chain is designed, synthesized by reference to the histone deacetylase (HDAC) inhibitor structure mode through selective demethylation, substitution, hydrazolysis, acylation, cyclization, elimination, condensation reaction. The structures of these synthetic derivatives were characterized and confirmed by 1H NMR (nuclear magnetic resonance), 13C NMR, and MS (mass spectrometry) spectral data and finally evaluated for antitumor activities against MHCC97H, HCC827, HELA, and HEL cell in vitro by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) method. The results demonstrated that target compound 8 exhibited better antiproliferative activity against the MHCC97H cell line, with a half maximal inhibitory concentration (IC50) = 5.4 ± 0.45 μM L–1 superior to berberine, and the activity against MHCC97H was nearly close to the reference drug doxorubicin. Through the dynamics of molecular docking and simulation, further analysis has demonstrated that the target compound 8 can form effective interactions with the HDAC6 target protein, and the results of binding free energy also revealed a strong affinity between the compound 8 and the HDAC6 protein. The results of this study suggest that compound 8 may be a potential inhibitor of HDAC6, which could have promising applications in the treatment of certain cancers.
Photochromic microcapsules adjust to sunlight adaptively and using them to fill windows is an attractive option for constructing smart windows that can manage solar heat and daylight. However, fabricating high-durability polymer-composite photochromic microcapsules for use in outdoor glass windows remains challenging, requiring high contrast ratio, high transparency, and low haze. Herein, we synthesized a novel poly(ureasiloxane) shell monomer containing Si -O -Si bonds and successfully prepared a photochromic microcapsule by modulating the mass ratios of shell monomers and emulsifiers. The photochromic poly(urea-siloxane)-based microcapsule-coated glass (PCPUS MCG) showed high luminance transmittance (83.66 %) and low haze (20.31 %). The as-prepared PCPUS MCG exhibited self-adaptive sunlight control without additional energy input, with strong solar modulation ability ( Delta tau sol of 38.30 %). Furthermore, the response indoor air temperature was reduced by approximately 3.7 degrees C in a field test using a model house equipped with PCPUS MCG windows, showing promising energy-saving potential compared with conventional windows. Therefore, uniform photochromic-microcapsule modification using Si -O -Si bonds warrants attention in future energy-saving window designs.
Combined photothermal therapy and nitric oxide (NO)-mediated gas therapy has shown great potential as a cancer treatment. However, the on-demand release of NO at a high concentration presents a challenge owing to the lack of an ideal bio-transducer with a high loading capacity of NO donors and sufficient energy to induce NO release. Here, we present a new 2D BiTiS3 nanosheet that is synthesized, loaded with the NO donor (BNN6), and conjugated with PEG-iRGD to produce a multifunctional bio-transducer (BNN6-BiTiS3-iRGD) for the on-demand production of NO. The BiTiS3 nanosheets not only have a high loading capacity of NO donors (750%), but also exhibit a high photothermal conversion efficiency (59.5%) after irradiation by a 1064-nm laser at 0.5 W/cm2. As a result of the above advantages, the temporal-controllable generation of NO within a large dynamic range (from 0 to 344 μM) is achieved by adjusting power densities, which is among the highest efficiency values reported for NO generators so far. Moreover, the targeted accumulation of BNN6-BiTiS3-iRGD at tumor sites leads to spatial-controllable NO release. In vitro and in vivo assessments demonstrate synergistic NO gas therapy with mild photothermal therapy based on BNN6-BiTiS3-iRGD. Our work provides insights into the design and application of other 2D nanomaterial-based therapeutic platforms.
The measurement of cardiac troponin I (cTnI) is of vital importance for the early diagnosis of acute myocardial infarction. In this study, an enhanced electrochemiluminescent immunoassay for the highly sensitive and precise determination of cTnI was reported. A biomimetic chip with nepenthes peristome surface microstructures to achieve single-layer microbead arrays and integrated microelectrode arrays (MEAs) for ECL detection was microfabricated. Ru@SiO2 nanoparticles were prepared as signal amplificators labeling immunomagnetic beads. Dendrimer-encapsulated platinum nanoparticles (Pt DENs) were electrochemically modified on ITO MEAs. The resulting Pt DEN-modified ITO MEAs preserved good optical transparency and exhibited an approximately 20-fold ECL signal amplification compared to that obtained from bare ITO. The method made full use of the biomimetic chip with Pt DENs to develop single-layer immunomagnetic bead arrays with increasingly catalyzed electrochemical oxidation of the [Ru(bpy)3]2+–TPA system. Consequently, a limit of detection calculated as 0.38 pg/mL (S/N = 3) was obtained with excellent selectivity, demonstrating significant potential for the detection of cTnI in clinical diagnostics.
Terpyridine and its derivatives have good binding affinity for most transition metal ions due to the arrangement of their three pyridine nitrogen atoms. In this work, a new ratiometric fluorescent probe G, which is based on a styrylpyridinium attached to a terpyridine fluorophore, was synthesized and characterized. The fluorescence spectrum of probe G shows a good response to Zn2+ by an intramolecular charge transfer effect. On increasing the concentration of Zn2+, the fluorescence color of probe G changes from blue to yellow. Importantly, probe G has a high selectivity for Zn2+and is not affected by other metal ions, including Cd2+. In addition, the limit of detection (LOD) of probe G for Zn2+ was found to be up to 0.17 µM. The results show that probe G has the ability to selectively recognize Zn2+ in aqueous solution.
Four new sesquiterpene lactones (SLs) (1–4), along with a biosynthetically related SL (5), have been isolated from the leaves of Magnolia grandiflora. Magrandate A (1) is notable as the first C18 homogemarane type SL, featuring a unique 1,7-dioxaspiro[4.4]nonan-6-one core. Compounds 2 and 3, representing the first instances of chlorine-substituted gemarane-type SL analogs in natural products, were also identified. The structures of these isolates were elucidated through a combination of spectroscopic data analysis, electronic circular dichroism calculations, and X-ray single-crystal diffraction analysis. All isolates demonstrated anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 cells. Notably, 3–5 showed a significant inhibitory effect on nitric oxide production, with IC50 values ranging from 0.79 to 4.73 μmol·L−1. Additionally, 4 and 5 exhibited moderate cytotoxic activities against three cancer cell lines, with IC50 values between 3.09 and 11.23 μmol·L−1.
Host-guest recognition-based macrocycle in macrocycle to form “Russian Doll” assemblies remains an interesting topic in supramolecular chemistry. Herein, a macrocycle-in-macrocycle assembly was studied using cucurbit[10]uril (Q[10]) and the smallest cucurbituril-like macrocycle (TD[4]). X-ray crystal structure analysis revealed that TD[4] was encapsulated in the cavity of Q[10] to form a 1:1 complex. Importantly, competitive guest studies suggested that TD[4] had the highest binding constant with the Q[10] host among the guests used, including Q[5], Me8TD[4], and amantadine molecules in water. Our results provided a new cucurbituril-based Russian-doll structure containing both the largest and smallest cavities of the cucurbiturils, which expanded the family of molecular Russian dolls.
As a common tumor with high incidence, osteosarcoma possesses extremely poor prognosis and high mortality. Improving the survival of osteosarcoma patients is still a great challenge due to the precipice of advancement in treatment. In this study, a combination strategy of gene therapy and photothermal therapy (PTT) is developed for efficient treatment of osteosarcoma. Two-dimensional (2D) FePS 3 nanosheets are synthesized and functionalized by poly-L-lysine-PEG-folic acid (PPF) to fabricate a multifunctional nanoplatform (FePS@PPF) for further loading microRNAs inhibitor, miR-19a inhibitor (anti-miR-19a). The photothermal conversion efficiency of FePS@PPF is up to 47.1% under irradiation by 1064 nm laser. In vitro study shows that anti-miR-19a can be efficiently internalized into osteosarcoma cells through the protection and delivery of FePS@PPF nanaocarrier, which induces up-regulation of PTEN protein and down-regulation p-AKT protein. After intravenous injection, the FePS@PPF nanoplatform specifically accumulates to tumor site of osteosarcoma-bearing mice. The in vitro and in vivo investigations reveal that the combined PTT-gene therapy displays most significant tumor ablation compared with monotherapy. More importantly, the good biodegradability promotes FePS@PPF to be cleared from body avoiding potential toxicity of long-term retention. Our work not only develops a combined strategy of NIR-II PTT and gene therapy mediated by anti-miR-19a/FePS@PPF but also provides insights into the design and applications of other nanotherapeutic platforms.