Surface and Interface Coordination Chemistry Learned from Model Heterogeneous Metal Nanocatalysts: From Atomically Dispersed Catalysts to Atomically Precise Clusters.

The surface and interface coordination structures of heterogeneous metal catalysts are crucial to their catalytic performance. However, the complicated surface and interface structures of heterogeneous catalysts make it challenging to identify the molecular-level structure of their active sites and thus precisely control their performance. To address this challenge, atomically dispersed metal catalysts (ADMCs) and ligand-protected atomically precise metal clusters (APMCs) have been emerging as two important classes of model heterogeneous catalysts in recent years, helping to build bridge between homogeneous and heterogeneous catalysis. This review illustrates how the surface and interface coordination chemistry of these two types of model catalysts determines the catalytic performance from multiple dimensions. The section of ADMCs starts with the local coordination structure of metal sites at the metal-support interface, and then focuses on the effects of coordinating atoms, including their basicity and hardness/softness. Studies are also summarized to discuss the cooperativity achieved by dual metal sites and remote effects. In the section of APMCs, the roles of surface ligands and supports in determining the catalytic activity, selectivity, and stability of APMCs are illustrated. Finally, some personal perspectives on the further development of surface coordination and interface chemistry for model heterogeneous metal catalysts are presented.

Neuronal small extracellular vesicles carrying miR-181c-5p contribute to the pathogenesis of epilepsy by regulating the protein kinase C-δ/glutamate transporter-1 axis in astrocytes.

Information exchange between neurons and astrocytes mediated by extracellular vesicles (EVs) is known to play a key role in the pathogenesis of central nervous system diseases. A key driver of epilepsy is the dysregulation of intersynaptic excitatory neurotransmitters mediated by astrocytes. Thus, we investigated the potential association between neuronal EV microRNAs (miRNAs) and astrocyte glutamate uptake ability in epilepsy. Here, we showed that astrocytes were able to engulf epileptogenic neuronal EVs, inducing a significant increase in the glutamate concentration in the extracellular fluid of astrocytes, which was linked to a decrease in glutamate transporter-1 (GLT-1) protein expression. Using sequencing and gene ontology (GO) functional analysis, miR-181c-5p was found to be the most significantly upregulated miRNA in epileptogenic neuronal EVs and was linked to glutamate metabolism. Moreover, we found that neuronal EV-derived miR-181c-5p interacted with protein kinase C-delta (PKCδ), downregulated PKCδ and GLT-1 protein expression and increased glutamate concentrations in astrocytes both in vitro and in vivo. Our findings demonstrated that epileptogenic neuronal EVs carrying miR-181c-5p decrease the glutamate uptake ability of astrocytes, thus promoting susceptibility to epilepsy.

Self-Driven Electric Field Control of Orbital Electrons in AuPd Alloy Nanoparticles for Cancer Catalytic Therapy.

The free radical generation efficiency of nanozymes in cancer therapy is crucial, but current methods fall short. Alloy nanoparticles (ANs) hold promise for improving catalytic performance due to their inherent electronic effect, but there are limited ways to modulate this effect. Here, a self-driven electric field (E) system utilizing triboelectric nanogenerator (TENG) and AuPd ANs with glucose oxidase (GOx)-like, catalase (CAT)-like, and peroxidase (POD)-like activities is presented to enhance the treatment of 4T1 breast cancer in mice. The E stimulation from TENG enhances the orbital electrons of AuPd ANs, resulting in increased CAT-like, GOx-like, and POD-like activities. Meanwhile, the catalytic cascade reaction of AuPd ANs is further amplified after catalyzing the production of H2 O2 from the GOx-like activities. This leads to 89.5% tumor inhibition after treatment. The self-driven E strategy offers a new way to enhance electronic effects and improve cascade catalytic therapeutic performance of AuPd ANs in cancer therapy.

Zinc-Based ROS Amplifiers Trigger Cancer Chemodynamic/Ion Interference Therapy Through Self-Cascade Catalysis.

Nanozyme-mediated chemodynamic therapy has emerged as a promising strategy due to its tumor specificity and controlled catalytic activity. However, the poor efficacy caused by low hydrogen peroxide (H2O2) levels in the tumor microenvironment (TME) poses challenges. Herein, an H2O2 self-supplying nanozyme is constructed through loading peroxide-like active platinum nanoparticles (Pt NPs) on zinc peroxide (ZnO2) (denoted as ZnO2@Pt). ZnO2 releases H2O2 in response to the acidic TME. Pt NPs catalyze the hydroxyl radical generation from H2O2 while reducing the mitigation of oxidative stress by glutathione, serving as a reactive oxygen (ROS) amplifier through self-cascade catalysis. In addition, Zn2+ released from ZnO2 interferes with tumor cell energy supply and metabolism, enabling ion interference therapy to synergize with chemodynamic therapy. In vitro studies demonstrate that ZnO2@Pt induces cellular oxidative stress injury through enhanced ROS generation and Zn2+ release, downregulating ATP and NAD+ levels. In vivo assessment of anticancer effects showed that ZnO2@Pt could generate ROS at tumor sites to induce apoptosis and downregulate energy supply pathways associated with glycolysis, resulting in an 89.7% reduction in tumor cell growth. This study presents a TME-responsive nanozyme capable of H2O2 self-supply and ion interference therapy, providing a paradigm for tumor-specific nanozyme design.

Probiotic Clostridium butyricum ameliorates cognitive impairment in obesity via the microbiota-gut-brain axis.

Obesity is a risk factor for cognitive dysfunction and neurodegenerative disease, including Alzheimer's disease (AD). The gut microbiota-brain axis is altered in obesity and linked to cognitive impairment and neurodegenerative disorders. Here, we targeted obesity-induced cognitive impairment by testing the impact of the probiotic Clostridium butyricum, which has previously shown beneficial effects on gut homeostasis and brain function. Firstly, we characterized and analyzed the gut microbial profiles of participants with obesity and the correlation between gut microbiota and cognitive scores. Then, using an obese mouse model induced by a Western-style diet (high-fat and fiber-deficient diet), the effects of Clostridium butyricum on the microbiota-gut-brain axis and hippocampal cognitive function were evaluated. Finally, fecal microbiota transplantation was performed to assess the functional link between Clostridium butyricum remodeling gut microbiota and hippocampal synaptic protein and cognitive behaviors. Our results showed that participants with obesity had gut microbiota dysbiosis characterized by an increase in phylum Proteobacteria and a decrease in Clostridium butyricum, which were closely associated with cognitive decline. In diet-induced obese mice, oral Clostridium butyricum supplementation significantly alleviated cognitive impairment, attenuated the deficit of hippocampal neurite outgrowth and synaptic ultrastructure, improved hippocampal transcriptome related to synapses and dendrites; a comparison of the effects of Clostridium butyricum in mice against human AD datasets revealed that many of the genes changes in AD were reversed by Clostridium butyricum; concurrently, Clostridium butyricum also prevented gut microbiota dysbiosis, colonic barrier impairment and inflammation, and attenuated endotoxemia. Importantly, fecal microbiota transplantation from donor-obese mice with Clostridium butyricum supplementation facilitated cognitive variables and colonic integrity compared with from donor obese mice, highlighting that Clostridium butyricum's impact on cognitive function is largely due to its ability to remodel gut microbiota. Our findings provide the first insights into the neuroprotective effects of Clostridium butyricum on obesity-associated cognitive impairments and neurodegeneration via the gut microbiota-gut-brain axis.

Oxytocin modulates social brain network correlations in resting and task state.

The effects of oxytocin (OT) on the social brain can be tracked upon assessing the neural activity in resting and task states, and developing a system-level framework for characterizing the state-based functional relationships of its distinct effect. Here, we contribute to this framework by examining how OT modulates social brain network correlations during resting and task states, using fMRI. First, we investigated network activation, followed by an analysis of the relationships between networks and individual differences. Subsequently, we evaluated the functional connectivity in both states. Finally, the relationship between networks across states was represented by the predictive power of networks in the resting state for task-evoked activities. The differences in the predicted accuracy between the subjects displayed individual variations in this relationship. Our results showed that the activity of the dorsal default mode network in the resting state had the largest predictive power for task-evoked activation of the precuneus network (PN) only in the OT group. The results also demonstrated that OT reduced the individual variation in PN in the prediction process. These findings suggest a distributed but modulatory effect of OT on the association between resting and task-dependent brain networks.

Predicting haemorrhagic transformation through serum biochemical indices for patients after endovascular treatment: a retrospective study.

INTRODUCTION: The aim of this study was to determine the serum biochemical markers that can predict the risk of haemorrhagic transformation (HT) before and after endovascular treatment (EVT). MATERIAL AND METHODS: This study included patients with anterior circulation large vessel occlusion (ACLVO) who underwent EVT within six hours of symptom onset between September 2017 and September 2022. These patients were retrospectively categorised into two groups: an HT group and a No-HT group. RESULTS: A total of 180 patients were included in the study, of whom 55 (30.6%) had HT. The monocyte count before EVT (p = = 0.005, OR = 0.694, 95% CI 0.536-0.898), the activated partial thromboplastin time before EVT (p = 0.009, OR = 0.186, 95% CI 0.699-0.952), and the eosinophil count after EVT (p = 0.038, OR = 0.001, 95% CI 0.000-0.018) were all found to be independent predictors of HT, with warning values of 6.65%, 22.95 seconds, and 0.035*10^9/L, respectively. When compared to prediction using only demographic data [AUC = 0.662,95% CI (0.545, 0.780)], adding biochemical indices before EVT [AUC = 0.719,95% CI (0.617, 0.821)], adding biochemical indices after EVT [AUC = 0.670,95% CI (0.566, 0.773)], and adding both [AUC = 0.778,95% CI (0.686, 0.870)], the prediction efficiency of HT was improved among all three combinations, with no statistical significance. CONCLUSIONS: The levels of serum biochemical markers were found to show significant changes before and after EVT in ACLVO patients. A combination of demographic data and serum biochemical markers proved to be effective in predicting the occurrence of HT in patients with ACLVO who underwent EVT.

Full Selectivity Control over the Catalytic Hydrogenation of Nitroaromatics into Six Products.

A full selectivity control over the catalytic hydrogenation of nitroaromatics leads to the production of six possible products, i.e., nitroso, hydroxylamine, azoxy, azo, hydrazo or aniline compounds, which has however not been achieved in the field of heterogeneous catalysis. Currently, there is no sufficient evidence to support that the catalytic hydrogenation of nitroaromatics with the use of heterogeneous metal catalysts would follow the Haber's mechanistic scheme based on electrochemical reduction. We now demonstrate in this work that it is possible to fully control the catalytic hydrogenation of nitroaromatics into their all six products using a single catalytic system under various conditions. Employing SnO2-supported Pt nanoparticles facilitated by the surface coordination of ethylenediamine and vanadium species enabled this unprecedented selectivity control. Through systematic investigation into the controlled production of all products and their chemical reactivities, we have constructed a detailed reaction network for the catalytic hydrogenation of nitroaromatics. Crucially, the application of oxygen-isolated characterization techniques proved indispensable in identifying unstable compounds such as nitroso, hydroxylamine, hydrazo compounds. The insights gained from this research offer invaluable guidance for selectively transforming nitroaromatics into a wide array of functional N-containing compounds, both advancing fundamental understanding and fostering practical applications in various fields.

Nanozyme-Based Colorimetric SARS-CoV-2 Nucleic Acid Detection by Naked Eye.

Fluorescence-based PCR and other amplification methods have been used for SARS-CoV-2 diagnostics, however, it requires costly fluorescence detectors and probes limiting deploying large-scale screening. Here, a cut-price colorimetric method for SARS-CoV-2 RNA detection by iron manganese silicate nanozyme (IMSN) is established. IMSN catalyzes the oxidation of chromogenic substrates by its peroxidase (POD)-like activity, which is effectively inhibited by pyrophosphate ions (PPi). Due to the large number of PPi generated by amplification processes, SARS-CoV-2 RNA can be detected by a colorimetric readout visible to the naked eye, with the detection limit of 240 copies mL-1 . This conceptually new method has been successfully applied to correctly distinguish positive and negative oropharyngeal swab samples of COVID-19. Colorimetric assay provides a low-cost and instrumental-free solution for nucleic acid detection, which holds great potential for facilitating virus surveillance.

Biomimetic Nanobomb for Synergistic Therapy with Inhibition of Cancer Stem Cells.

Cancer stem cells (CSCs), a type of cell with self-renewal, unlimited proliferation, and insensitivity to common physical and chemical factors, are the key to cancer metastasis, recurrence, and chemo-resistance. Available CSCs inhibition strategies are mainly based on small molecule drugs, yet are limited by their off-target toxicity. The link between CSCs and non-CSCs interconversion is difficult to sever. In this work, a nanotherapeutic strategy based on MnOx -loaded polydopamine (MnOx /PDA) nanobombs with chemodynamic, photodynamic, photothermal and biodegradation properties to inhibit CSCs and non-CSCs concurrently is reported. The MnOx /PDA nanobombs can directly disrupt the microenvironment and tumorigenic capacity of CSCs by generating hyperthermia, oxidative stress and alleviating hypoxia. The markers of CSCs are subsequently downregulated, leading to the clearance of CSCs. Meanwhile, the synergistic therapy mediated by MnOx /PDA nanobombs can directly ablate the bulk tumor cells, thus cutting off the supply of CSCs transformation. For tumor targeting, MnOx /PDA is coated with macrophage membrane. The final tumor inhibition rate of the synergistic therapy is 70.8% in colorectal cancer (CRC) model. Taken together, the present work may open up the exploration of nanomaterial-based synergistic therapy for the simultaneous elimination of therapeutically resistant CSCs and non-CSCs.

N-Heterocyclic Carbene-Stabilized Gold Nanoclusters with Organometallic Motifs for Promoting Catalysis.

The complexity of heterogeneous metal catalysts makes it challenging to gain insights into their catalytic mechanisms. Thus, there exists a huge gap between heterogeneous catalysis and organometallic catalysis. With the success in the preparation of highly robust atomically precise metal nanocluster catalysts (i.e., [Au16(NHC-1)5(PA)3Br2]3+ and [Au17(NHC-1)4(PA)4Br4]+, where NHC-1 is a bidentate NHC ligand, and PA is phenylacetylide) with surface organometallic motifs anchored on the metallic core, we demonstrate in this work how the metallic core works synergistically with the surface organometallic motifs to enhance the catalysis. More importantly, the discovery allows the development of highly stable and recyclable heterogeneous metal catalysts to achieve efficient hydroamination of alkynes with an extremely low catalyst dosage (0.002 mol %), helping bridge the gap between heterogeneous and homogeneous metal catalysis. The surface modification of metal nanocatalysts with organometallic motifs provides a new design principle of metal catalysts with enhanced catalysis.

Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1/Nrf2/HO-1/Gpx4 pathway.

BACKGROUND: The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis of depression. Edaravone (EDA), a free radical scavenger, processes strong biological activities including antioxidant, anti-inflammatory and neuroprotective properties. However, its role and potential molecular mechanisms in depression remain unclear. The present study aimed to investigate the antidepressant activity of EDA and its underlying mechanisms. METHODS: A chronic social defeat stress (CSDS) depression model was performed to explore whether EDA could produce antidepressant effects. Behaviors tests were carried out to examine depressive, anxiety-like and cognitive behaviors including social interaction (SI) test, sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM), novel object recognition (NOR), tail suspension test (TST) and forced swim test (FST). Hippocampal and medial prefrontal cortex (mPFC) tissues were collected for Nissl staining, immunofluorescence, targeted energy metabolomics analysis, enzyme-linked immunosorbent assay (ELISA), measurement of MDA, SOD, GSH, GSH-PX, T-AOC and transmission electron microscopy (TEM). Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) detected the Sirt1/Nrf2/HO-1/Gpx4 signaling pathway. EX527, a Sirt1 inhibitor and ML385, a Nrf2 inhibitor were injected intraperitoneally 30 min before EDA injection daily. Knockdown experiments were performed to determine the effects of Gpx4 on CSDS mice with EDA treatment by an adeno-associated virus (AAV) vector containing miRNAi (Gpx4)-EGFP infusion. RESULTS: The administrated of EDA dramatically ameliorated CSDS-induced depressive and anxiety-like behaviors. In addition, EDA notably attenuated neuronal loss, microglial activation, astrocyte dysfunction, oxidative stress damage, energy metabolism and pro-inflammatory cytokines activation in the hippocampus (Hip) and mPFC of CSDS-induced mice. Further examination indicated that the application of EDA after the CSDS model significantly increased the protein expressions of Sirt1, Nrf2, HO-1 and Gpx4 in the Hip. EX527 abolished the antidepressant effect of EDA as well as the protein levels of Nrf2, HO-1 and Gpx4. Similarly, ML385 reversed the antidepressant and anxiolytic effects of EDA via decreased expressions of HO-1 and Gpx4. In addition, Gpx4 knockdown in CSDS mice abolished EDA-generated efficacy on depressive and anxiety-like behaviors. CONCLUSION: These findings suggest that EDA possesses potent antidepressant and anxiolytic properties through Sirt1/Nrf2/HO-1/Gpx4 axis and Gpx4-mediated ferroptosis may play a key role in this effect.

Surface Coordination Chemistry of Atomically Dispersed Metal Catalysts.

Atomically dispersed metal catalysts (ADCs), as an emerging class of heterogeneous catalysts, have been widely investigated during the past two decades. The atomic dispersion nature of the catalytic metal centers makes them an ideal system for bridging homogeneous and heterogeneous metal catalysts. The recent rapid development of new synthetic strategies has led to the explosive growth of ADCs with a wide spectrum of metal atoms dispersed on supports of different chemical compositions and natures. The availability of diverse ADCs creates a powerful materials platform for investigating mechanisms of complicated heterogeneous catalysis at the atomic levels. Considering most dispersed metal atoms on ADCs are coordinated by the donors from supports, this review will demonstrate how the surface coordination chemistry plays an important role in determining the catalytic performance of ADCs. This review will start from the link between coordination chemistry and heterogeneous catalysis. After the brief description on the advantages and limitations of common structure characterization methods in determining the coordination structure of ADCs, the surface coordination chemistry of ADCs on different types of supports will be discussed. We will mainly illustrate how the local and vicinal coordination species on different support systems act together with the dispersed catalytic metal center to determine the catalytic activity, selectivity, and stability of ADCs. The dynamic coordination structure change of ADCs in catalysis will be highlighted. At the end of the review, personal perspectives on the further development of the field of ADCs will be provided.

Diagnosis and minimally invasive treatment of type III choledochal cysts.

BACKGROUND: Type III choledochal cysts (CCs) are the rarest and least well-characterized of the five variants of biliary cysts. Only a few relevant studies have been conducted and a gold standard treatment for type III CCs is still lacking because of their scarcity. An unusual case of type III CC with choledochocele at the end of the distal common bile duct (CBD) with no bulging of the duodenum is presented here. CASE PRESENTATION: A 61-year-old woman presented to our department with repeated upper abdominal pain for one year. Laboratory examination revealed abnormal liver function and a slight increase in the white blood cell (WBC) count and proportion of neutrophils. In an MRCP of the patient, the distal CBD was found to have a cystic structure indicative of a type III CC. Endoscopic retrograde cholangiopancreatograpy (ERCP) revealed cystic findings compatible with Todani type III CCs. However, duodenoscopy did not show a bulge in the duodenum so laparoscopic cholecystectomy and Roux-en-Y hepaticojejunostomy were performed. In her 6-month follow-up, the patient reported that recovery from the operation was uneventful. CONCLUSIONS: ERCP has become the gold standard for diagnosing type III CCs. Type III CCs can be treated minimally invasively with laparoscopic cholecystectomy and Roux-en-Y hepaticojejunostomy.

MicroRNA Transcriptomics Analysis Identifies Dysregulated Hedgehog Signaling Pathway in a Mouse Model of Acute Intracerebral Hemorrhage Exposed to Hyperglycemia.

OBJECTIVE: Hyperglycemia is often observed in the patients after acute stroke. This study aims to elucidate the potential effect and mechanism of hyperglycemia by screening microRNAs expression in intracerebral hemorrhage mice. METHODS: We employed the collagenase model of intracerebral hemorrhage. Twenty male C57BL/6 mice were used and randomly divided in normo- and hyperglycemic. The hyperglycemia was induced by intraperitoneally injection of 50% of Dextrose (8 mL/kg) 3 hours after intracerebral hemorrhage. The neurologic impairment was investigated by neurologic deficit scale. To study the specific mechanisms of hyperglycemia, microRNAs expression in perihematomal area was investigated by RNA sequencing. MicroRNAs expression in hyperglycemic intracerebral hemorrhage animals were compared normoglycemic mice. Functional annotation analysis was used to indicate potential pathological pathway, underlying observed effects. Finally, polymerase chain reaction validation was administered. RESULTS: Intraperitoneal injection of dextrose significantly increased blood glucose level. That was associated with aggravation of neurological deficits in hyperglycemic compared to normoglycemic animals. A total of 73 differentially expressed microRNAs were identified via transcriptomics analysis. Bioinformatics analyses showed that these microRNAs were significantly altered in several signaling pathways, of which the hedgehog signaling pathway was regarded as the most potential pathway associated with the effect of hyperglycemia on acute intracerebral hemorrhage. Furthermore, polymerase chain reaction results validated the correlation between microRNAs and hedgehog signaling pathway. CONCLUSIONS: MicroRNA elevated in hyperglycemia group may be involved in worsening the neurological function via inhibiting the hedgehog signaling, which provides a novel molecular physiological mechanism and lays the foundation for treatment of intracerebral hemorrhage.

A Photoresponsive Nanozyme for Synergistic Catalytic Therapy and Dual Phototherapy.

Dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has shown a great prospect in cancer treatment. However, its therapeutic effect is restricted by the depth of light penetration in tissue and tumor hypoxia environment. Herein, inspired by the specific response of nanozymes to the tumor microenvironment (TME), a simple and versatile nanozyme-mediated synergistic dual phototherapy nanoplatform (denoted as FePc/HNCSs) is constructed using hollow nitrogen-doped carbon nanospheres (HNCSs) and iron phthalocyanine (FePc). FePc/HNCSs simultaneously exhibit peroxidase (POD)- and catalase (CAT)-like activities, which not only can convert endogenous hydrogen peroxide (H2 O2 ) into highly toxic hydroxyl radicals (•OH) for catalytic therapy, but also decompose H2 O2 to oxygen (O2 ) to enhance O2 -dependent PDT. In addition, their enzyme-like activities are significantly enhanced under light irradiation. Combining with the excellent photothermal effect, FePc/HNCSs realize a high tumor inhibition rate of 96.3%. This strategy opens a new horizon for exploring a more powerful tumor treatment nanoplatform.

Surface Coordination of Multiple Ligands Endows N-Heterocyclic Carbene-Stabilized Gold Nanoclusters with High Robustness and Surface Reactivity.

Deciphering the molecular pictures of the multi-component and non-periodic organic-inorganic interlayer is a grand technical challenge. Here we show that the atomic arrangement of hybrid surface ligands on metal nanoparticles can be precisely quantified through comprehensive characterization of a novel gold cluster, Au44 (i Pr2 -bimy)9 (PA)6 Br8 (1), which features three types of ligands, namely, carbene (1,3-diisopropylbenzimidazolin-2-ylidene, i Pr2 -bimy), alkynyl (phenylacetylide, PA), and halide (Br), respectively. The delicately balanced stereochemical effects and bonding capabilities of the three ligands give rise to peculiar geometrical and electronic structures. Remarkably, despite its complex and highly distorted surface structure, cluster 1 exhibits unusual catalytic properties and yet it is highly stable, both chemically and thermally. Moreover, rich reactive sites on the cluster surface raise the prospect of bio-compatibility (as it can be functionalized to yield water-soluble derivatives) and bio-applications.

Biodegradable Nanocomposite with Dual Cell-Tissue Penetration for Deep Tumor Chemo-Phototherapy.

Chemo-phototherapy, as a promising cancer combination therapy strategy, has attracted widespread attention. However, the complex tumor microenvironment restricts the penetration depth of chemo-phototherapy agents in the tumor region. Here, biodegradable amphiphilic gelatin (AG) wrapped nanocomposite (PRDCuS@AG) composed of doxorubicin and copper sulfide (CuS)-loaded dendrimer is designed for deep tumor chemo-phototherapy. PR in PRDCuS@AG represents arginine-conjugated polyamidoamine dendrimer. PRDCuS@AG can rapidly biodegrade into PRDCuS by matrix metalloproteinases under near-infrared light irradiation. The resulted PRDCuS harbors dual cell-tissue penetration ability, which can effectively penetrate deep into the tumor tissue. In particular, PRDCuS@AG achieves photoacoustic imaging-guided synergistic chemo-phototherapy with 97% of tumor inhibition rate. Moreover, PRDCuS@AG can further degrade into 3 nm ultrasmall CuS, which can be eliminated from the body after treatment to avoid side effects. This strategy provides an insight that the development of chemo-phototherapy agents with high penetration ability to overcome the limitation of current deep tumor therapy.

Rosmarinic Acid, the Main Effective Constituent of Orthosiphon stamineus, Inhibits Intestinal Epithelial Apoptosis Via Regulation of the Nrf2 Pathway in Mice.

Many studies have shown that Orthosiphon stamineus extract (OE) has antioxidant activity, and we previously reported that OE protects the intestine against injury from a high-fat diet. However, the molecular mechanism underlying this protective effect of OE was unclear. Here, OE was separated according to polarity and molecular weight, and the antioxidant activity of each component was compared. The components with the highest antioxidant activity were analyzed by HPLC, which confirmed that rosmarinic acid (RA) was the main effective constituent in OE. OE and RA were then tested in a mouse high-fat diet-induced intestinal injury model. The antioxidant indices and morphological characteristics of the mouse jejunum were measured, and activation of the nuclear factor E2-related factor 2 (Nrf2) pathway and apoptosis of jejunal epithelial cells were analyzed. Of all the constituents in OE, RA contributed the most. Both RA and OE activated the Nrf2 pathway and increased downstream antioxidant enzyme activity. RA and OE protected the mouse intestine against high-fat diet-induced oxidative stress by preventing intestinal epithelial cell apoptosis via both extracellular and intracellular pathways. Thus, RA, the main effective constituent in OE, inhibits intestinal epithelial apoptosis by regulating the Nrf2 pathway in mice.

A Nanozyme with Photo-Enhanced Dual Enzyme-Like Activities for Deep Pancreatic Cancer Therapy.

Nanozymes have attracted extensive interest owing to their high stability, low cost and easy preparation, especially in the field of cancer therapy. However, the relatively low catalytic activity of nanozymes in the tumor microenvironment (TME) has limited their applications. Herein, we report a novel nanozyme (PtFe@Fe3 O4 ) with dual enzyme-like activities for highly efficient tumor catalytic therapy. PtFe@Fe3 O4 shows the intrinsic photothermal effect as well as photo-enhanced peroxidase-like and catalase-like activities in the acidic TME, thereby effectively killing tumor cells and overcoming the tumor hypoxia. Importantly, a possible photo-enhanced synergistic catalytic mechanism of PtFe@Fe3 O4 was first disclosed. We believe that this work will advance the development of nanozymes in tumor catalytic therapy.