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.

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.

Nanoconfinement-Guided Construction of Nanozymes for Determining H2 O2 Produced by Sonication.

Nanomaterials with enzyme-like activities, termed as nanozymes, have found wide applications in various fields. It has been a long-term aim to rationally design and synthesize highly active nanozymes and thus to further improve their application performance. Guided by the nanoconfinement effect, we confine cytochrome c (Cyt c) within a mesoporous metal-organic framework (MOF), PCN-222 nanoparticle (NP), forming a protein/MOF hybrid nanozyme, termed as Cyt c@PCN-222 NP. The confined Cyt c exhibits around 3-4-fold higher peroxidase-like activity than free Cyt c. Due to the increase in the activity of Cyt c, the Cyt c@PCN-222 NPs exhibit a quite low limit of detection (≈0.13 µM) towards H2 O2 . Sonication-induced H2 O2 formation in water by using a lab-quipped ultrasonic cleaner can be sensitively probed, which suggests that H2 O2 -sensitive materials should be carefully handled during the utilization of ultrasonic equipment. We speculate that this nanoconfinement strategy can broaden our synthetic methodology for the rational design of nanozymes.

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.

Quantification of Intracellular Proteins in Single Cells Based on Engineered Picoliter Droplets.

Unlike conventional bulk measurements, single-cell protein analysis permits quantification of protein expression in individual cells. This has shed light on the cell-to-cell variation in heterogeneous biological systems, such as solid tumors, brain tissues, and developing embryos. Herein, a microfluidic method is developed to profile protein expression in individual cells by performing single-cell intracellular protein immunoassay in picoliter paired droplets. The high sensitivity of single-cell protein analysis on a chip is achieved by the confined reaction volume of picoliter droplets, efficient kinetic characteristics of the immunoassay through active mixing, and minimum single-cell protein loss by integrated operations. The abundance of an intracellular prostate specific antigen at the single-cell level is measured, and then the platform is applied to identify cell types and investigate heterogeneity within cell populations. Overall, a paired chip for single-cell immunoassay establishes a foundation for parallel, sensitive, and integrated protein quantification at the single-cell level and will find wide applications in the field of single-cell proteomics.

Uniform Core-Shell Microspheres of SiO2@MOF for CO2 Cycloaddition Reactions.

A SiO2@MOF core-shell microsphere for environmentally friendly applications was introduced in this study. Several types of metal-organic framework core-shell microspheres were successfully synthesized. To achieve high stability and favorable catalytic performance, modification and coating methods were necessary for optimization. The improved SiO2@MOF core-shell microspheres were used in the cycloaddition reaction of carbon dioxide and propylene oxide. Dispersion ability was enhanced by the addition of core-shell microspheres, which also produced high catalytic activity. Accompanied with tetrabutylammonium bromide as a co-catalyst, SiO2@ZIF-67 had a maximum conversion of 97%, and the results revealed that SiO2@ZIF-67 could be used for 5 reaction cycles while maintaining high catalytic performance. This recycling catalyst was also reacted with a series of terminal epoxides to form corresponding cyclic carbonates with high conversion rates, indicating that SiO2@MOF core-shell microspheres exhibit promise in the field of catalysis.

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.

The Cooperativity of Fe3 O4 and Metal-Organic Framework as Multifunctional Nanocomposites for Laser Desorption Ionization Process.

A novel and facile strategy in developing a water stable magnetic metal-organic framework nanocomposite (Fe3 O4 @MOF) is herein reported, in which a Keggin polyoxometalate, phosphotungstic acid (HPW), was encapsulated within the MOF framework via one-pot synthesis method. The combination of HPW-embedded MOF and Fe3 O4 endowed the composite with high surface area, strong UV absorption, good hydrophilicity, and enhanced water stability. With these unique properties, the Fe3 O4 @MOF embedded HPW served as adsorbent as well as matrix for SALDI-MS (surface-assisted laser desorption ionization mass spectrometry) analysis of polar and non-polar compounds. The synergistic effect of Fe3 O4 and MOF showed an interference-free background at low mass region than the pristine MOF or Fe3 O4 counterparts. This simple approach can be used as new platform in developing magnetic MOF composites without the time consuming and labor-intensive preparation.

Monitoring the Effect of Different Metal Centers in Metal-Organic Frameworks and Their Adsorption of Aromatic Molecules using Experimental and Simulation Studies.

In this study, the adsorption behavior of different metal centers in analogous M-1,4-NDC frameworks (1,4-NDC=1,4-naphthalenedicarboxylate) towards guest molecules through simulation studies and experimental studies is reported. Simulation studies showed that the adsorption behavior of analogous M-1,4-NDC is affected by the atomic radius of the metal center, which was found to be in agreement with the experimental studies.

Category-selective patterns of neural response in the ventral visual pathway in the absence of categorical information.

Neuroimaging studies have revealed distinct patterns of response to different object categories in the ventral visual pathway. These findings imply that object category is an important organizing principle in this region of visual cortex. However, object categories also differ systematically in their image properties. So, it is possible that these patterns of neural response could reflect differences in image properties rather than object category. To differentiate between these alternative explanations, we used images of objects that had been phase-scrambled at a local or global level. Both scrambling processes preserved many of the lower-level image properties, but rendered the images unrecognizable. We then measured the effect of image scrambling on the patterns of neural response within the ventral pathway. We found that intact and scrambled images evoked distinct category-selective patterns of activity in the ventral stream. Moreover, intact and scrambled images of the same object category produced highly similar patterns of response. These results suggest that the neural representation in the ventral visual pathway is tightly linked to the statistical properties of the image.

Nanoporous Carbons Derived from Metal-Organic Frameworks as Novel Matrices for Surface-Assisted Laser Desorption/Ionization Mass Spectrometry.

Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) represents a powerful tool for the analysis of biomolecules, synthetic polymers, and even small organic compounds; its performances largely depend on the type of matrix materials utilized. Here, for the first time the employment of nanoporous carbons derived from metal-organic frameworks (MOFs) as novel matrices for SALDI-MS is demonstrated. The nanoporous carbons derived from MOFs not only circumvent the shortcomings of existing matrix materials but also demonstrate much higher efficiency of laser desorption/ionization for various compounds than any other nanoporous carbons reported so far. A new perspective for the development of matrix materials for SALDI-MS application is therefore provided.

Lipase-supported metal-organic framework bioreactor catalyzes warfarin synthesis.

A green and sustainable strategy synthesizes clinical medicine warfarin anticoagulant by using lipase-supported metal-organic framework (MOF) bioreactors (see scheme). These findings may be beneficial for future studies in the industrial production of chemical, pharmaceutical, and agrochemical precursors.

Determination of amino acids by microemulsion electrokinetic chromatography laser induced fluorescence method.

In this study, detection of 20 FITC-derivatized amino acids using an MEEKC-LIF was demonstrated. In order to achieve good separation for hydrophobic amino acids, the MEEKC method was employed and detection limits were obtained in the range of 0.32-2.2 nM, which is comparable to previous reports on amino acid analyses. Furthermore, a significant reduction in the reaction time from 1 h for conventional derivatization to 3 min for the microwave-assisted derivatization was observed and achieved, as opposed to the traditional pretreatment of real sample due to its complexity prior to the analysis of amino acid content. Finally, this microwave-assisted derivatization MEEKC-LIF method successfully determined amino acids in beverage, food, and biological samples (rat brain) with good recovery.

Fast multipoint immobilized MOF bioreactor.

An enzyme-NBD@MOF bioreactor with exemplary proteolytic performance, even after successive reuse and storage, was produced through a novel, rapid and simple multipoint immobilization technique without chemical modification of the solid support. Enzyme loading and distribution could be directly monitored from the fluorescence emission of the bioreactor. The dye molecular dimension plays a role in its overall performance.

A phenomenological model of pulsatile blood pressure-affected degradation of polylactic acid (PLA) vascular stent.

The stent implantation may alter the post-operative patient's blood pressure, and bioresorbable vascular stents (BVS) as a candidate to treat vascular diseases, its degradation is affected by mechanical stress, thus, the altered pressure representing varying stress level will result in different degradation behaviors of the BVS. This paper first proposed a novel stress-regulated PLA degradation model that included swelling factor, and then the degradation evolutions of a PLA BVS within 180 days under normal and high blood pressures were simulated by finite element method, and more four degradation indexes were defined to study the effects of the two blood pressures on the degradation of the PLA BVS. The results showed that the high pressure weakly accelerated the degradation of the PLA BVS with respect to the normal pressure by examining the four indexes, e.g., the residual stent volume v r ( t ) decreased to 0.72 and 0.69, respectively for the normal and high pressures at day 180. The current finding provided a theoretical understanding of the PLA BVS degradation, and hinted that the PLA BVS may not need to be elaborately selected in clinical practices for treating hypertensive patients.

The Critical Role of the Shroom Family Proteins in Morphogenesis, Organogenesis and Disease.

The Shroom (Shrm) family of actin-binding proteins has a unique and highly conserved Apx/Shrm Domain 2 (ASD2) motif. Shroom protein directs the subcellular localization of Rho-associated kinase (ROCK), which remodels the actomyosin cytoskeleton and changes cellular morphology via its ability to phosphorylate and activate non-muscle myosin II. Therefore, the Shrm-ROCK complex is critical for the cellular shape and the development of many tissues, including the neural tube, eye, intestines, heart, and vasculature system. Importantly, the structure and expression of Shrm proteins are also associated with neural tube defects, chronic kidney disease, metastasis of carcinoma, and X-link mental retardation. Therefore, a better understanding of Shrm-mediated signaling transduction pathways is essential for the development of new therapeutic strategies to minimize damage resulting in abnormal Shrm proteins. This paper provides a comprehensive overview of the various Shrm proteins and their roles in morphogenesis and disease.

Bioinspired Nanozymes as Nanodecoys for Urinary Tract Infection Treatment.

Urinary tract infections (UTIs), common bacterial infections in communities and medical facilities, are mainly mediated by FimH. The glycan sites of the uromodulin protein play a crucial role in protecting against UTIs by interacting with FimH. A bioinspired approach using glycan-FimH interactions may effectively reduce bacteria through an antiadhesive mechanism, thereby curbing bacterial resistance. However, typical antiadhesive therapy alone fails to address the excessive reactive oxygen species and inflammatory response during UTIs. To bridge this gap, antioxidant nanozymes with antiadhesive ability were developed as nanodecoys to counter bacteria and inflammation. Specifically, ultrasmall dextran-coated ceria (DEC) was engineered to address UTIs, with dextran blocking FimH adhesion and ceria exhibiting anti-inflammatory properties. DECs, metabolizable by the kidneys, reduced bacterial content in the urinary tract, mitigating inflammation and tissue damage. In murine models, DECs successfully treated acute UTIs, repeated infections, and catheter-related UTIs. This dual approach not only highlights the potential of nanozymes for UTIs but also suggests applicability to other FimH-induced infections in the lungs and bowels, marking a significant advancement in nanozyme-based clinical approaches.

Rare Earth Nanoprobes for Targeted Delineation of Triple Negative Breast Cancer and Enhancement of Radioimmunotherapy.

Radiotherapy demonstrates a synergistic effect with immunotherapy by inducing a transformation of "immune cold" tumors into "immune hot" tumors in triple negative breast cancer (TNBC). Nevertheless, the effectiveness of immunotherapy is constrained by low expression of tumor-exposed antigens, inadequate inflammation, and insufficient tumor infiltrating lymphocyte (TILs). To address this predicament, novel lutecium-based rare earth nanoparticles (RENPs) are synthesized with the aim of amplifying radiation effect and tumor immune response. The nanoprobe is characterized by neodymium-based down-conversion fluorescence, demonstrating robust photostability, biocompatibility, and targetability. The conjugation of RENPs with a CXCR4 targeted drug enables precise delineation of breast tumors using a near-infrared imaging system and improves radiation efficacy via lutetium-based radio-sensitizer in vivo. Furthermore, the study shows a notable enhancement of immune response through the induction of immunogenic cell death and recruitment of TILs, resulting in the inhibition of tumor progression both in vitro and in vivo models following the administration of nanoparticles. Hence, the novel multifunctional nanoprobes incorporating various lanthanide elements offer the potential for imaging-guided tumor delineation, radio-sensitization, and immune activation post-radiation, thus presenting an efficient radio-immunotherapeutic approach for TNBC.

Linking between soil properties, bacterial communities, enzyme activities, and soil organic carbon mineralization under ecological restoration in an alpine degraded grassland.

Soil organic carbon (SOC) mineralization is affected by ecological restoration and plays an important role in the soil C cycle. However, the mechanism of ecological restoration on SOC mineralization remains unclear. Here, we collected soils from the degraded grassland that have undergone 14 years of ecological restoration by planting shrubs with Salix cupularis alone (SA) and, planting shrubs with Salix cupularis plus planting mixed grasses (SG), with the extremely degraded grassland underwent natural restoration as control (CK). We aimed to investigate the effect of ecological restoration on SOC mineralization at different soil depths, and to address the relative importance of biotic and abiotic drivers of SOC mineralization. Our results documented the statistically significant impacts of restoration mode and its interaction with soil depth on SOC mineralization. Compared with CK, the SA and SG increased the cumulative SOC mineralization but decreased C mineralization efficiency at the 0-20 and 20-40 cm soil depths. Random Forest analyses showed that soil depth, microbial biomass C (MBC), hot-water extractable organic C (HWEOC), and bacterial community composition were important indicators that predicted SOC mineralization. Structural equal modeling indicated that MBC, SOC, and C-cycling enzymes had positive effects on SOC mineralization. Bacterial community composition regulated SOC mineralization via controlling microbial biomass production and C-cycling enzyme activities. Overall, our study provides insights into soil biotic and abiotic factors in association with SOC mineralization, and contributes to understanding the effect and mechanism of ecological restoration on SOC mineralization in a degraded grassland in an alpine region.