Additional file 1 of Effect of online intervention mode on breastfeeding results: a systematic review and meta-analysis

Additional file 1: Methods

Data-Driven Evolutionary Design of Multienzyme-like Nanozymes

Multienzyme-like nanozymes are nanomaterials with multiple enzyme-like activities and are the focus of nanozyme research owing to their ability to facilitate cascaded reactions, leverage synergistic effects, and exhibit environmentally responsive selectivity. However, multienzyme-like nanozymes exhibit varying enzyme-like activities under different conditions, making them difficult to precisely regulate according to the design requirements. Moreover, individual enzyme-like activity in a multienzyme-like activity may accelerate, compete, or antagonize each other, rendering the overall activity a complex interplay of these factors rather than a simple sum of single enzyme-like activity. A theoretically guided strategy is highly desired to accelerate the design of multienzyme-like nanozymes. Herein, nanozyme information was collected from 4159 publications to build a nanozyme database covering element type, element ratio, chemical valence, shape, pH, etc. Based on the clustering correlation coefficients of the nanozyme information, the material features in distinct nanozyme classifications were reorganized to generate compositional factors for multienzyme-like nanozymes. Moreover, advanced methods were developed, including the quantum mechanics/molecular mechanics method for analyzing the surface adsorption and binding energies of substrates, transition states, and products in the reaction pathways, along with machine learning algorithms to identify the optimal reaction pathway, to aid the evolutionary design of multienzyme-like nanozymes. This approach culminated in creating CuMnCo7O12, a highly active multienzyme-like nanozyme. This process is named the genetic-like evolutionary design of nanozymes because it resembles biological genetic evolution in nature and offers a feasible protocol and theoretical foundation for constructing multienzyme-like nanozymes

Data-Driven Evolutionary Design of Multienzyme-like Nanozymes

Multienzyme-like nanozymes are nanomaterials with multiple enzyme-like activities and are the focus of nanozyme research owing to their ability to facilitate cascaded reactions, leverage synergistic effects, and exhibit environmentally responsive selectivity. However, multienzyme-like nanozymes exhibit varying enzyme-like activities under different conditions, making them difficult to precisely regulate according to the design requirements. Moreover, individual enzyme-like activity in a multienzyme-like activity may accelerate, compete, or antagonize each other, rendering the overall activity a complex interplay of these factors rather than a simple sum of single enzyme-like activity. A theoretically guided strategy is highly desired to accelerate the design of multienzyme-like nanozymes. Herein, nanozyme information was collected from 4159 publications to build a nanozyme database covering element type, element ratio, chemical valence, shape, pH, etc. Based on the clustering correlation coefficients of the nanozyme information, the material features in distinct nanozyme classifications were reorganized to generate compositional factors for multienzyme-like nanozymes. Moreover, advanced methods were developed, including the quantum mechanics/molecular mechanics method for analyzing the surface adsorption and binding energies of substrates, transition states, and products in the reaction pathways, along with machine learning algorithms to identify the optimal reaction pathway, to aid the evolutionary design of multienzyme-like nanozymes. This approach culminated in creating CuMnCo7O12, a highly active multienzyme-like nanozyme. This process is named the genetic-like evolutionary design of nanozymes because it resembles biological genetic evolution in nature and offers a feasible protocol and theoretical foundation for constructing multienzyme-like nanozymes

Ortho-Substituted α‑Phenyl Mannoside Derivatives Promoted Early-Stage Adhesion and Biofilm Formation of <i>E. coli</i> 83972

Prevention of catheter-associated urinary tract infection (CAUTI) over long-term usage of urinary catheters remains a great challenge. Bacterial interference using nonpathogenic bacteria, such as E. coli 83972, have been investigated in many pilot-scale clinical studies as a potentially nonantibiotic based strategy for CAUTI prevention. We have demonstrated that preforming a dense and stable biofilm of the nonpathogenic E. coli greatly enhances their capability to prevent pathogen colonization. Such nonpathogenic biofilms were formed by E. coli 83972 expressing type 1 fimbriae (fim+ E. coli 83972) on mannoside-presenting surfaces. In this work, we report the synthesis of a series of mannoside derivatives with a wide range of binding affinities, all being equipped with a handle for covalent attachment to silicone surfaces. We established a high-throughput competitive assay based on mannoside-modified particles and flow-cytometry to directly measure the binding affinity between the mannoside ligands and fim+ E. coli 83972. We demonstrated that the bacterial adhesion and biofilm formation were strongly correlated to the binding affinity of the immobilized mannoside ligands. Mass spectrometry based proteomic analysis indicated a substantial difference in the proteome of the extracellular polymeric substance (EPS) secreted by biofilms on different mannoside surfaces, which might be related to the biofilm stability

Ultrasound-Augmented Multienzyme-like Nanozyme Hydrogel Spray for Promoting Diabetic Wound Healing

Treatment of diabetic foot ulcers (DFU) needs to reduce inflammation, relieve hypoxia, lower blood glucose, promote angiogenesis, and eliminate pathogenic bacteria, but the therapeutic efficacy is greatly limited by the diversity and synergy of drug functions as well as the DFU microenvironment itself. Herein, an ultrasound-augmented multienzyme-like nanozyme hydrogel spray was developed using hyaluronic acid encapsulated l-arginine and ultrasmall gold nanoparticles and Cu1.6O nanoparticles coloaded phosphorus doped graphitic carbon nitride nanosheets (ACPCAH). This nanozyme hydrogel spray possesses five types of enzyme-like activities, including superoxide dismutase (SOD)-, catalase (CAT)-, glucose oxidase (GOx)-, peroxidase (POD)-, and nitric oxide synthase (NOS)-like activities. The kinetics and reaction mechanism of the sonodynamic/sonothermal synergistic enhancement of the SOD-CAT-GOx-POD/NOS cascade reaction of ACPCAH are fully investigated. Both in vitro and in vivo tests demonstrate that this nanozyme hydrogel spray can be activated by the DFU microenvironment to reduce inflammation, relieve hypoxia, lower blood glucose, promote angiogenesis, and eliminate pathogenic bacteria, thus accelerating diabetic wound healing effectively. This study highlights a competitive approach based on multienzyme-like nanozymes for the development of all-in-one DFU therapies

Nonmetal Graphdiyne Nanozyme-Based Ferroptosis–Apoptosis Strategy for Colon Cancer Therapy

Ferroptosis–apoptosis, a new modality of induced cell death dependent on reactive oxygen species, has drawn tremendous attention in the field of nanomedicine. A metal-free ferroptosis–apoptosis inducer was reported based on boron and nitrogen codoped graphdiyne (BN-GDY) that possesses efficient glutathione (GSH) depletion capability and concurrently induces ferroptosis by deactivation of GSH-dependent peroxidases 4 (GPX4) and apoptosis by downregulation of Bcl2. The high catalytic activity of BN-GDY is explicated by both kinetic experiments and density functional theory (DFT) calculations of Gibbs free energy change during hydrogen peroxide (H2O2) decomposition. In addition, a unique sequence Bi–Bi mechanism is discovered, which is distinct from the commonly reported ping-pong Bi–Bi mechanism of most peroxidase mimics and natural enzymes. We anticipate that this nonmetal ferroptosis–apoptosis therapeutic concept by carbon-based nanomaterials would provide proof-of-concept evidence for nanocatalytic medicines in cancer therapy

Machine Learning Guided Discovery of Superoxide Dismutase Nanozymes for Androgenetic Alopecia

Androgenetic alopecia (AGA) is a common form of hair loss, which is mainly caused by oxidative stress induced dysregulation of hair follicles (HF). Herein, a highly efficient manganese thiophosphite (MnPS3) based superoxide dismutase (SOD) mimic was discovered using machine learning (ML) tools. Remarkably, the IC50 of MnPS3 is 3.61 μg·mL–1, up to 12-fold lower than most reported SOD-like nanozymes. Moreover, a MnPS3 microneedle patch (MnMNP) was constructed to treat AGA that could diffuse into the deep skin where HFs exist and remove excess reactive oxygen species. Compared with the widely used minoxidil, MnMNP exhibits higher ability on hair regeneration, even at a reduced frequency of application. This study not only provides a general guideline for the accelerated discovery of SOD-like nanozymes by ML techniques, but also shows a great potential as a next generation approach for rational design of nanozymes

Extent of the Oxidative Side Reactions to Peptides and Proteins During the CuAAC Reaction

The copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction is a powerful tool for bioconjugation of biomolecules, particularly proteins and peptides. The major drawback limiting the use of the CuAAC reaction in biological systems is the copper-mediated formation of reactive oxygen species (ROS), leading to the oxidative degradation of proteins or peptides. From the studies on a limited number of proteins and peptides, it is known that, in general, the copper mediated oxidative damage is associated with the copper coordination environment and solvent accessibility. However, there is a lack of data to help estimate the extent of copper-mediated oxidation on a wide range of proteins and peptides. To begin to address this need, we quantitatively measured the degree of copper-mediated oxidation on libraries of 1200 tetrapeptides and a model protein (bovine serum albumin, BSA) using liquid chromatography mass spectrometry (LC-MS). The collected data will be useful to researchers planning to use the CuAAC reaction for bioconjugaton on peptides or proteins

Piezoelectric Activatable Nanozyme-Based Skin Patch for Rapid Wound Disinfection

Nanozymes are promising new-generation antibacterial agents owing to their low cost, high stability, broad-spectrum activity, and minimal antimicrobial resistance. However, the inherent low catalytic activity of nanozymes tends to limit their antibacterial efficacy. Herein, a heterostructure of zinc oxide nanorod@graphdiyne nanosheets (ZnO@GDY NR) with unparallel piezocatalytic enzyme mimic activity is reported, which concurrently possesses intrinsic peroxidase-like activity and strong piezoelectric responses and effectively promotes the decomposition of hydrogen peroxide (H2O2) and generation of reactive oxygen species under ultrasound irradiation. Moreover, this piezocatalytic nanozyme exhibits almost 100% antibacterial efficacy against multidrug-resistant pathogens involving methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa in vitro and in vivo. In addition, a piezoelectric activatable nanozyme-based skin patch is developed for rapid skin wound disinfections with satisfactory hemocompatibility and cytocompatibility. This work not only sheds light on the development of an innovative piezoelectric activatable nanozyme-based skin patch for rapid wound disinfection but also provides new insights on the engineering of piezocatalytic nanozymes for nanozyme antibacterial therapy