Nanozyme-Enhanced Probiotic Spores Regulate the Intestinal Microenvironment for Targeted Acute Gastroenteritis Therapy.

Antibiotic therapeutics to combat intestinal pathogen infections often exacerbate microbiota dysbiosis and impair mucosal barrier functions. Probiotics are promising strategies, because they inhibit pathogen colonization and improve intestinal microbiota imbalance. Nevertheless, their limited targeting ability and susceptibility to oxidative stress have hindered their therapeutic potential. To tackle these challenges, Ces3 is synthesized by in situ growth of CeO2 nanozymes with positive charges on probiotic spores, facilitating electrostatic interactions with negatively charged pathogens and possessing a high reactive oxygen species (ROS) scavenging activity. Importantly, Ces3 can resist the harsh environment of the gastrointestinal tract. In mice with S. Typhimurium-infected acute gastroenteritis, Ces3 shows potent anti-S. Typhimurium activity, thereby alleviating the dissemination of S. Typhimurium into other organs. Additionally, owing to its O2 deprivation capacity, Ces3 promotes the proliferation of anaerobic probiotics, reshaping a healthy intestinal microbiota. This work demonstrates the promise of combining antibacterial, anti-inflammatory, and O2 content regulation properties for acute gastroenteritis therapy.

Site-Specific Antibody Prodrugs via S-Arylation: a Bioconjugation Approach Toward Masked Tyrosine Analogues.

The utility of antibody therapeutics is hampered by potential cross-reactivity with healthy tissue. Over the past decade, significant advances have been made in the design of activatable antibodies, which increase, or create altogether, the therapeutic window of a parent antibody. Of these, antibody prodrugs (pro-antibodies) are masked antibodies that have advanced the most for therapeutic use. They are designed to reveal the active, parent antibody only when encountering proteases upregulated in the microenvironment of the targeted disease tissue, thereby minimizing off-target activity. However, current pro-antibody designs are relegated to fusion proteins that append masking groups restricted to the use of only canonical amino acids, offering excellent control of the site of introduction, but with no authority over where the masking group is installed other than the N-terminus of the antibody. Here, we present a palladium-based bioconjugation approach for the site-specific introduction of a masked tyrosine mimic in the complementary determining region of the FDA approved antibody therapeutic ipilimumab used as a model system. The approach enables the introduction of a protease cleavable group tethered to noncanonical polymers (polyethylene glycol (PEG)) resulting in 47-fold weaker binding to cells expressing CTLA-4, the target antigen of ipilimumab. Upon exposure to tumor-associated proteases, the masking group is cleaved, unveiling a tyrosine-mimic (dubbed hydroxyphenyl cysteine (HPC)) that restores (>90% restoration) binding affinity to its target antigen.

A Self-Cascade Oxygen-Generating Nanomedicine for Multimodal Tumor Therapy.

Natural and artificial enzyme oxygen-generating systems for photodynamic therapy (PDT) are developed for tumor treatment, yet they have fallen short of the desired efficacy. Moreover, both the enzymes and photosensitizers usually need carriers for efficient delivery to tumor sites. Here, a self-cascade-enhanced multimodal tumor therapy is developed by ingeniously integrating self-cascade-enhanced PDT with Zn2+-overloading therapy. Manganese-porphyrin (TCPP-Mn) is chosen both as the photosensitizer and catalase (CAT) mimic, which can be encapsulated within glucose oxidase (GOx). Acid-responsive zeolitic imidazolate framework-8 (ZIF-8) is applied as the carrier for TCPP-Mn@GOx (T@G), attaining TCPP-Mn@GOx@ZIF-8 (T@G@Z). T@G@Z demonstrates robust anti-tumor ability as follows: upon the structural degradation of ZIF-8, GOx can mediate the oxidation of glucose and generate hydrogen peroxide (H2O2); TCPP-Mn can catalyze H2O2 into O2 for self-cascade-enhanced PDT; meanwhile, the released Zn2+ can enhance oxidative stress and induce mitochondrial dysfunction by destroying mitochondrial membrane potential; furthermore, immunotherapy can be activated to resist primary tumor and tumor metastasis. The self-cascade-enhanced T@G@Z exhibited its potential application for further tumor management.

D-1553: A novel KRASG12C inhibitor with potent and selective cellular and in vivo antitumor activity.

D-1553 is a small molecule inhibitor selectively targeting KRASG12C and currently in phase II clinical trials. Here, we report the preclinical data demonstrating antitumor activity of D-1553. Potency and specificity of D-1553 in inhibiting GDP-bound KRASG12C mutation were determined by thermal shift assay and KRASG12C -coupled nucleotide exchange assay. In vitro and in vivo antitumor activity of D-1553 alone or in combination with other therapies were evaluated in KRASG12C mutated cancer cells and xenograft models. D-1553 showed selective and potent activity against mutated GDP-bound KRASG12C protein. D-1553 selectively inhibited ERK phosphorylation in NCI-H358 cells harboring KRASG12C mutation. Compared to the KRAS WT and KRASG12D cell lines, D-1553 selectively inhibited cell viability in multiple KRASG12C cell lines, and the potency was slightly superior to sotorasib and adagrasib. In a panel of xenograft tumor models, D-1553, given orally, showed partial or complete tumor regression. The combination of D-1553 with chemotherapy, MEK inhibitor, or SHP2 inhibitor showed stronger potency on tumor growth inhibition or regression compared to D-1553 alone. These findings support the clinical evaluation of D-1553 as an efficacious drug candidate, both as a single agent or in combination, for patients with solid tumors harboring KRASG12C mutation.

Platinum-Nickel Nanoparticles with Enhanced Oxidase-like Activity for Total Antioxidant Capacity Bioassay.

While great progress in nanozyme-enabled analytical chemistry has been made, most current nanozyme-based biosensing platforms are based on peroxidase-like nanozymes. However, peroxidase-like nanozymes with multienzymatic activities can influence the detection sensitivity and accuracy, while the use of unstable hydrogen peroxide (H2O2) in a peroxidase-like catalytic reaction may result in the reproducibility challenge of sensing signals. We envision that constructing biosensing systems by using oxidase-like nanozymes can address these limitations. Herein, we reported that platinum-nickel nanoparticles (Pt-Ni NPs) with Pt-rich shells and Ni-rich cores possessed high oxidase-like catalytic efficiency, exhibiting a 2.18-fold higher maximal reaction velocity (vmax) than initial pure Pt NPs. The oxidase-like Pt-Ni NPs were applied to develop a colorimetric assay for the determination of total antioxidant capacity (TAC). The antioxidant levels of four bioactive small molecules, two antioxidant nanomaterials, and three cells were successfully measured. Our work not only provides new insights for preparing highly active oxidase-like nanozymes but also manifests their applications for TAC analysis.

Nanozyme-Enabled Treatment of Cardio- and Cerebrovascular Diseases.

Cardio- and cerebrovascular diseases are two major vascular-related diseases that lead to death worldwide. Reactive oxygen species (ROS) play a vital role in the occurrence and exacerbation of diseases. Excessive ROS induce cellular context damage and lead to tissue dysfunction. Nanozymes, as emerging enzyme mimics, offer a unique perspective for therapy through multifunctional activities, achieving essential results in the treatment of ROS-related cardio- and cerebrovascular diseases by directly scavenging excess ROS or regulating pathologically related molecules. This review first introduces nanozyme-enabled therapeutic mechanisms at the cellular level. Then, the therapies for several typical cardio- and cerebrovascular diseases with nanozymes are discussed, mainly including cardiovascular diseases, ischemia reperfusion injury, and neurological disorders. Finally, the challenges and outlooks for the application of nanozymes are also presented. This review will provide some instructive perspectives on nanozymes and promote the development of enzyme-mimicking strategies in cardio- and cerebrovascular disease therapy.

Amyloid-ß oligomers in the nucleus accumbens decrease motivation via insertion of calcium-permeable AMPA receptors.

It is essential to identify the neuronal mechanisms of Alzheimer's Disease (AD)-associated neuropsychiatric symptoms, e.g., apathy, before improving the life quality of AD patients. Here, we focused on the nucleus accumbens (NAc), a critical brain region processing motivation, also known to display AD-associated pathological changes in human cases. We found that the synaptic calcium permeable (CP)-AMPA receptors (AMPARs), which are normally absent in the NAc, can be revealed by acute exposure to Aß oligomers (AßOs), and play a critical role in the emergence of synaptic loss and motivation deficits. Blockade of NAc CP-AMPARs can effectively prevent AßO-induced downsizing and pruning of spines and silencing of excitatory synaptic transmission. We conclude that AßO-triggered synaptic insertion of CP-AMPARs is a key mechanism mediating synaptic degeneration in AD, and preserving synaptic integrity may prevent or delay the onset of AD-associated psychiatric symptoms.

A deep learning method for the automated assessment of paradoxical pulsation after myocardial infarction using multicenter cardiac MRI data.

OBJECTIVE: The current study aimed to explore a deep convolutional neural network (DCNN) model that integrates multidimensional CMR data to accurately identify LV paradoxical pulsation after reperfusion by primary percutaneous coronary intervention with isolated anterior infarction. METHODS: A total of 401 participants (311 patients and 90 age-matched volunteers) were recruited for this prospective study. The two-dimensional UNet segmentation model of the LV and classification model for identifying paradoxical pulsation were established using the DCNN model. Features of 2- and 3-chamber images were extracted with 2-dimensional (2D) and 3D ResNets with masks generated by a segmentation model. Next, the accuracy of the segmentation model was evaluated using the Dice score and classification model by receiver operating characteristic (ROC) curve and confusion matrix. The areas under the ROC curve (AUCs) of the physicians in training and DCNN models were compared using the DeLong method. RESULTS: The DCNN model showed that the AUCs for the detection of paradoxical pulsation were 0.97, 0.91, and 0.83 in the training, internal, and external testing cohorts, respectively (p < 0.001). The 2.5-dimensional model established using the end-systolic and end-diastolic images combined with 2-chamber and 3-chamber images was more efficient than the 3D model. The discrimination performance of the DCNN model was better than that of physicians in training (p < 0.05). CONCLUSIONS: Compared to the model trained by 2-chamber or 3-chamber images alone or 3D multiview, our 2.5D multiview model can combine the information of 2-chamber and 3-chamber more efficiently and obtain the highest diagnostic sensitivity. CLINICAL RELEVANCE STATEMENT: A deep convolutional neural network model that integrates 2-chamber and 3-chamber CMR images can identify LV paradoxical pulsation which correlates with LV thrombosis, heart failure, ventricular tachycardia after reperfusion by primary percutaneous coronary intervention with isolated anterior infarction. KEY POINTS: • The epicardial segmentation model was established using the 2D UNet based on end-diastole 2- and 3-chamber cine images. • The DCNN model proposed in this study had better performance for discriminating LV paradoxical pulsation accurately and objectively using CMR cine images after anterior AMI compared to the diagnosis of physicians in training. • The 2.5-dimensional multiview model combined the information of 2- and 3-chamber efficiently and obtained the highest diagnostic sensitivity.

Aerobic capacity and [Formula: see text] kinetics adaptive responses to short-term high-intensity interval training and detraining in untrained females.

PURPOSE: This study investigated the physical fitness and oxygen uptake kinetics (τ[Formula: see text]) along with the O2 delivery and utilization (heart rate kinetics, τHR; deoxyhemoglobin/[Formula: see text] ratio, ∆[HHb]/[Formula: see text]) adaptations of untrained female participants responding to 4 weeks of high-intensity interval training (HIIT) and 2 weeks of detraining. METHODS: Participants were randomly assigned to HIIT (n = 11, 4 × 4 protocol) or nonexercising control (n = 9) groups. Exercising group engaged 4 weeks of treadmill HIIT followed by 2 weeks of detraining while maintaining daily activity level. Ramp-incremental (RI) tests and step-transitions to moderate-intensity exercise were performed. Aerobic capacity and performance (maximal oxygen uptake, [Formula: see text]; gas-exchange threshold, GET; power output, PO), body composition (skeletal muscle mass, SMM; body fat percentage, BF%), muscle oxygenation status (∆[HHb]), [Formula: see text], and HR kinetics were assessed. RESULTS: HIIT elicited improvements in aerobic capacity ([Formula: see text], + 0.17 ± 0.04 L/min; GET, + 0.18 ± 0.05 L/min, P < 0.01; PO-[Formula: see text], ± 23.36 ± 8.37 W; PO-GET, + 17.18 ± 3.07 W, P < 0.05), body composition (SMM, + 0.92 ± 0.17 kg; BF%, - 3.08% ± 0.58%, P < 0.001), and speed up the τ[Formula: see text] (- 8.04 ± 1.57 s, P < 0.001) significantly, extending to better ∆[HHb]/[Formula: see text] ratio (1.18 ± 0.08 to 1.05 ± 0.14). After a period of detraining, the adaptation in body composition and aerobic capacity, as well as the accelerated τ[Formula: see text] were maintained in the HIIT group, but the PO-[Formula: see text] and PO-GET declined below the post-training level (P < 0.05), whereas no changes were reported in controls (P > 0.05). Four weeks of HIIT induced widespread physiological adaptations in females, and the majority of improvements were preserved after 2 weeks of detraining except for power output corresponding to [Formula: see text] and GET.

Adaptations to 4 weeks of high-intensity interval training in healthy adults with different training backgrounds.

PURPOSE: This study investigated the physical fitness and oxygen uptake kinetics ([Formula: see text]) along with the exercise-onset O2 delivery (heart rate kinetics, τHR; changes in normalized deoxyhemoglobin/[Formula: see text] ratio, Δ[HHb]/[Formula: see text]) adaptations of individuals with different physical activity (PA) backgrounds responding to 4 weeks of high-intensity interval training (HIIT), and the possible effects of skeletal muscle mass (SMM) on training-induced adaptations. METHODS: Twenty subjects (10 high-PA level, HIIT-H; 10 moderate-PA level, HIIT-M) engaged in 4 weeks of treadmill HIIT. Ramp-incremental (RI) test and step-transitions to moderate-intensity exercise were performed. Cardiorespiratory fitness, body composition, muscle oxygenation status, VO2 and HR kinetics were assessed at baseline and post-training. RESULTS: HIIT improved fitness status for HIIT-H ([Formula: see text], + 0.26 ± 0.07 L/min; SMM, + 0.66 ± 0.70 kg; body fat, - 1.52 ± 1.93 kg; [Formula: see text], - 7.11 ± 1.05 s, p < 0.05) and HIIT-M ([Formula: see text], 0.24 ± 0.07 L/min, SMM, + 0.58 ± 0.61 kg; body fat, - 1.64 ± 1.37 kg; [Formula: see text], - 5.48 ± 1.05 s, p < 0.05) except for visceral fat area (p = 0.293) without between-group differences (p > 0.05). Oxygenated and deoxygenated hemoglobin amplitude during the RI test increased for both groups (p < 0.05) except for total hemoglobin (p = 0.179). The Δ[HHb]/[Formula: see text] overshoot was attenuated for both groups (p < 0.05) but only eliminated in HIIT-H (1.05 ± 0.14 to 0.92 ± 0.11), and no change was observed in τHR (p = 0.144). Linear mixed-effect models presented positive effects of SMM on absolute [Formula: see text] (p < 0.001) and ΔHHb (p = 0.034). CONCLUSION: Four weeks of HIIT promoted positive adaptations in physical fitness and [Formula: see text] kinetics, with the peripheral adaptations attributing to the observed improvements. The training effects are similar between groups suggesting that HIIT is effective for reaching higher physical fitness levels.

Effect of knee osteoarthritis on the postoperative outcome of proximal femoral nail anti-rotation in the treatment of intertrochanteric fractures in the elderly: a retrospective analysis.

BACKGROUND: The proximal femoral nail anti-rotation (PFNA) is a commonly used internal fixation system for intertrochanteric fractures (IFs) in older adults. Knee osteoarthritis (KOA) is a degenerative lower extremity disease that occurs most frequently in the elderly. Some patients have already had KOA before the IFs. However, whether KOA impacts the postoperative outcome of IFs has not been reported. OBJECTIVE: This study aimed to investigate the effect of KOA on the fracture side on the outcome after PFNA for IFs in the elderly. METHODS: Between January 2016 and November 2021, 297 elderly patients treated with PFNA for IFs were enrolled in this study. They were divided into two groups according to the American Rheumatism Association KOA clinical and radiographic criteria: the control group and the KOA group. Intraoperative bleeding, operative time, length of hospital stay, postoperative time out of bed, fracture healing time, postoperative complications, postoperative Harris hip function score, and Barthel ability to daily living Score were compared between the two groups. Follow-up was routinely scheduled at 1, 3, 6, and 12 months postoperatively. RESULTS: Based on the exclusion criteria, 254 patients who met the requirements were left to be included in this study, including the control group (n = 133) and the KOA group (n = 121). Patients were followed up for a mean of 17.5 months (12-24 months). There was no significant difference between the two groups in preoperative demographic data, intraoperative blood loss, operation time, and length of stay in the hospital. The control group was statistically significant compared to the KOA group in terms of postoperative time out of bed (17.8 ± 4.0 days vs. 19.1 ± 5.8 days), fracture healing time (13.7 ± 2.2 weeks vs. 14.6 ± 3.7 weeks), and postoperative complications (12.8 vs. 23.1%). The Harris hip function score and Barthel ability to daily living score were higher in the control group than in the KOA group at 1, 3, 6, and 12 months postoperatively (the control group: 63.8 ± 10.9, 71.8 ± 10.3, 81.5 ± 8.7, and 91.6 ± 6.3 vs. The KOA group 61.0 ± 10.4, 68.6 ± 9.1, 79.0 ± 9.2, and 88.5 ± 5.9). CONCLUSIONS: In elderly patients with IFs combined with KOA of the fracture side treated with PFNA internal fixation, KOA increases the incidence of postoperative complications of the fracture, prolongs postoperative time out of bed and fracture healing, and reduces postoperative hip function and ability to daily living. Therefore, treating KOA on the fractured side needs to be considered when treating IFs in the elderly.

Integrated Cascade Nanozymes with Antisenescence Activities for Atherosclerosis Therapy.

Senescent cells are the critical drivers of atherosclerosis formation and maturation. Mitigating senescent cells holds promise for the treatment of atherosclerosis. In an atherosclerotic plaque microenvironment, senescent cells interact with reactive oxygen species (ROS), promoting the disease development. Here, we hypothesize that a cascade nanozyme with antisenescence and antioxidant activities can serve as an effective therapeutic for atherosclerosis. An integrated cascade nanozyme with superoxide dismutase- and glutathione peroxidase-like activities, named MSe1 , is developed in this work. The obtained cascade nanozyme can attenuate human umbilical vein endothelial cell (HUVEC) senescence by protecting DNA from damage. It significantly weakens inflammation in macrophages and HUVECs by eliminating overproduced intracellular ROS. Additionally, the MSe1 nanozyme effectively inhibits foam cell formation in macrophages and HUVECs by decreasing the internalization of oxidized low-density lipoprotein. After intravenous administration, the MSe1 nanozyme significantly inhibits the formation of atherosclerosis in apolipoprotein E-deficient (ApoE-/- ) mice by reducing oxidative stress and inflammation and then decreases the infiltration of inflammatory cells and senescent cells in atherosclerotic plaques. This study not only provides a cascade nanozyme but also suggests that the combination of antisenescence and antioxidative stress holds considerable promise for treating atherosclerosis.

A Dopamine-Enabled Universal Assay for Catalase and Catalase-Like Nanozymes.

Developing a universal strategy to measure catalase (CAT)/CAT-like activity, on one hand, overcomes limitations on current assays, such as moderate sensitivity and limited sample scope; on the other hand, facilitates insightful studies on applications of CAT and CAT-like nanozymes. Herein, the oxygen-sensitive and H2O2-inhibitory self-polymerization of dopamine (DA) was demonstrated as an activity indicator of CAT or CAT-like nanozymes, which monitors the catalytically generated O2 in a hypoxic environment. A typical assay for natural CAT was achieved under the optimized conditions. Moreover, this assay was suitable for diverse types of samples, ranging from nanozymes, animal tissues, to human saliva. By comparing the merits and limitations of common methods, this assay shows all-round advantages in sensitivity, specificity, and versatility, facilitating the formulation of measurement criteria and the development of potential standardized assays for CAT (or CAT-like nanozyme) activity.

Inhibition of the hERG potassium channel by phenanthrene: a polycyclic aromatic hydrocarbon pollutant.

The lipophilic polycyclic aromatic hydrocarbon (PAH) phenanthrene is relatively abundant in polluted air and water and can access and accumulate in human tissue. Phenanthrene has been reported to interact with cardiac ion channels in several fish species. This study was undertaken to investigate the ability of phenanthrene to interact with hERG (human Ether-à-go-go-Related Gene) encoded Kv11.1 K+ channels, which play a central role in human ventricular repolarization. Pharmacological inhibition of hERG can be proarrhythmic. Whole-cell patch clamp recordings of hERG current (IhERG) were made from HEK293 cells expressing wild-type (WT) and mutant hERG channels. WT IhERG1a was inhibited by phenanthrene with an IC50 of 17.6 ± 1.7 µM, whilst IhERG1a/1b exhibited an IC50 of 1.8 ± 0.3 µM. WT IhERG block showed marked voltage and time dependence, indicative of dependence of inhibition on channel gating. The inhibitory effect of phenanthrene was markedly impaired by the attenuated inactivation N588K mutation. Remarkably, mutations of S6 domain aromatic amino acids (Y652, F656) in the canonical drug binding site did not impair the inhibitory action of phenanthrene; the Y652A mutation augmented IhERG block. In contrast, the F557L (S5) and M651A (S6) mutations impaired the ability of phenanthrene to inhibit IhERG, as did the S624A mutation below the selectivity filter region. Computational docking using a cryo-EM derived hERG structure supported the mutagenesis data. Thus, phenanthrene acts as an inhibitor of the hERG K+ channel by directly interacting with the channel, binding to a distinct site in the channel pore domain.

Structural and functional studies of TBC1D23 C-terminal domain provide a link between endosomal trafficking and PCH.

Pontocerebellar hypoplasia (PCH) is a group of neurological disorders that affect the development of the brain, in particular, the pons and cerebellum. Homozygous mutations of TBC1D23 have been found recently to lead to PCH; however, the underlying molecular mechanisms remain unclear. Here, we show that the crystal structure of the TBC1D23 C-terminal domain adopts a Pleckstrin homology domain fold and selectively binds to phosphoinositides, in particular, PtdIns(4)P, through one surface while binding FAM21 via the opposite surface. Mutation of key residues of TBC1D23 or FAM21 selectively disrupts the endosomal vesicular trafficking toward the Trans-Golgi Network. Finally, using the zebrafish model, we show that PCH patient-derived mutants, impacting either phosphoinositide binding or FAM21 binding, lead to abnormal neuronal growth and brain development. Taken together, our data provide a molecular basis for the interaction between TBC1D23 and FAM21, and suggest a plausible role for PtdIns(4)P in the TBC1D23-mediating endosome-to-TGN trafficking pathway. Defects in this trafficking pathway are, at least partially, responsible for the pathogenesis of certain types of PCH.

Research of Maritime Object Detection Method in Foggy Environment Based on Improved Model SRC-YOLO.

An improved maritime object detection algorithm, SRC-YOLO, based on the YOLOv4-tiny, is proposed in the foggy environment to address the issues of false detection, missed detection, and low detection accuracy in complicated situations. To confirm the model's validity, an ocean dataset containing various concentrations of haze, target angles, and sizes was produced for the research. Firstly, the Single Scale Retinex (SSR) algorithm was applied to preprocess the dataset to reduce the interference of the complex scenes on the ocean. Secondly, in order to increase the model's receptive field, we employed a modified Receptive Field Block (RFB) module in place of the standard convolution in the Neck part of the model. Finally, the Convolutional Block Attention Module (CBAM), which integrates channel and spatial information, was introduced to raise detection performance by expanding the network model's attention to the context information in the feature map and the object location points. The experimental results demonstrate that the improved SRC-YOLO model effectively detects marine targets in foggy scenes by increasing the mean Average Precision (mAP) of detection results from 79.56% to 86.15%.

Twitter-aided decision making: a review of recent developments.

Twitter is one of the largest online platforms where people exchange information. In the first few years since its emergence, researchers have been exploring ways to use Twitter data in various decision making scenarios, and have shown promising results. In this review, we examine 28 newer papers published in last five years (since 2016) that continued to advance Twitter-aided decision making. The application scenarios we cover include product sales prediction, stock selection, crime prevention, epidemic tracking, and traffic monitoring. We first discuss the findings presented in these papers, that is how much decision making performance has been improved with the help of Twitter data. Then we offer a methodological analysis that considers four aspects of methods used in these papers, including problem formulation, solution, Twitter feature, and information transformation. This methodological analysis aims to enable researchers and decision makers to see the applicability of Twitter-aided methods in different application domains or platforms.

A Valence-Engineered Self-Cascading Antioxidant Nanozyme for the Therapy of Inflammatory Bowel Disease.

Antioxidant treatment strategy by scavenging reactive oxygen species (ROS) is a highly effective disease treatment option. Nanozymes with multiple antioxidant activities can cope with the diverse ROS environment. However, lack of design strategies and limitation of negative correlation for nanozymes with multiple antioxidant activities hindered their development. To overcome these difficulties, here we used ZnMn2 O4 as a model to explore the role of Mn valency at the octahedral site via a valence-engineered strategy, and found that its multiple antioxidant activities are positively correlated with the content of Mn4+ . Therefore, through this strategy, a self-cascading antioxidant nanozyme LiMn2 O4 was constructed, and its efficacy was verified at the cellular level and in an inflammatory bowel disease model. This work not only provides guidance for the design of multiple antioxidant nanozymes, but also broadens the biomedical application potential of multiple antioxidant nanozymes.

Structurally Engineered Light-Responsive Nanozymes for Enhanced Substrate Specificity.

Mimicking enzyme specificity via construction of on-demand geometric structures on nanozymes is of great interest in recent years. Although building substrate-specific polymers on nanozymes has achieved great success, polymer-blocked active sites would inevitably lead to decreased activity of nanozymes. Here, we have developed three photoactive metal-organic framework (MOF)-based nanozymes (called 2D-TCPP, 3D-TCPP, and AD-TCPP), which have different geometric structures as well as unshielded active sites. Together with their structural variations and excellent photoresponsive oxidase-like activities, these photoactive nanozymes exhibit structure-dependent specificity for three kinds of substrates (typical oxidase substrates, organic pollutants, and antioxidants). Moreover, AD-TCPP and 3D-TCPP show potential applications for environmental protection and bioanalysis, respectively. This work offers a promising approach to the development of nanozymes with enzyme-like specificity.

Inorganic Enzyme Mimics.

Enzyme mimics (or artificial enzymes) have emerged as valuable alternatives to natural enzymes since the pioneering work of Ronald Breslow. They have numerous advantages over natural enzymes, such as high stability, low cost, and tailorable activity. Among varieties of materials explored to mimic enzymes, the inorganic ones, including inorganic complexes and nanomaterials, have attracted increasing interest over the last decade and have the potential to address the current challenges in energy, environment, health, etc.