Artificial Phages with Biocatalytic Spikes for Synergistically Eradicating Antibiotic-Resistant Biofilms.

Antibiotic-resistant pathogens have become a global public health crisis, especially biofilm-induced refractory infections. Efficient, safe, and biofilm microenvironment (BME)-adaptive therapeutic strategies are urgently demanded to combat antibiotic-resistant biofilms. Here, inspired by the fascinating biological structures and functions of phages, the de novo design of a spiky Ir@Co3O4 particle is proposed to serve as an artificial phage for synergistically eradicating antibiotic-resistant Staphylococcus aureus biofilms. Benefiting from the abundant nanospikes and highly active Ir sites, the synthesized artificial phage can simultaneously achieve efficient biofilm accumulation, extracellular polymeric substance (EPS) penetration, and superior BME-adaptive reactive oxygen species (ROS) generation, thus facilitating the in situ ROS delivery and enhancing the biofilm eradication. Moreover, metabolomics found that the artificial phage obstructs the bacterial attachment to EPS, disrupts the maintenance of the BME, and fosters the dispersion and eradication of biofilms by down-regulating the associated genes for the biosynthesis and preservation of both intra- and extracellular environments. The in vivo results demonstrate that the artificial phage can treat the biofilm-induced recalcitrant infected wounds equivalent to vancomycin. It is suggested that the design of this spiky artificial phage with synergistic "penetrate and eradicate" capability to treat antibiotic-resistant biofilms offers a new pathway for bionic and nonantibiotic disinfection.

Polyoxometalate-Structured Materials: Molecular Fundamentals and Electrocatalytic Roles in Energy Conversion.

Polyoxometalates (POMs), a kind of molecular metal oxide cluster with unique physical-chemical properties, have made essential contributions to creating efficient and robust electrocatalysts in renewable energy systems. Due to the fundamental advantages of POMs, such as the diversity of molecular structures and large numbers of redox active sites, numerous efforts have been devoted to extending their application areas. Up to now, various strategies of assembling POM molecules into superstructures, supporting POMs on heterogeneous substrates, and POMs-derived metal compounds have been developed for synthesizing electrocatalysts. From a multidisciplinary perspective, the latest advances in creating POM-structured materials with a unique focus on their molecular fundamentals, electrocatalytic roles, and the recent breakthroughs of POMs and POM-derived electrocatalysts, are systematically summarized. Notably, this paper focuses on exposing the current states, essences, and mechanisms of how POM-structured materials influence their electrocatalytic activities and discloses the critical requirements for future developments. The future challenges, objectives, comparisons, and perspectives for creating POM-structured materials are also systematically discussed. It is anticipated that this review will offer a substantial impact on stimulating interdisciplinary efforts for the prosperities and widespread utilizations of POM-structured materials in electrocatalysis.

Spiky Artificial Peroxidases with V-O-Fe Pair Sites for Combating Antibiotic-Resistant Pathogens.

With the sharp rise of antibiotic-resistant pathogens worldwide, it is of enormous importance to create new strategies for combating pathogenic bacteria. Here, we create an iron oxide-based spiky artificial peroxidase (POD) with V-O-Fe pair sites (V-Fe2 O3 ) for combating methicillin-resistant Staphylococcus aureus (MRSA). The experimental studies and theoretical calculations demonstrate that the V-Fe2 O3 can achieve the localized "capture and killing" bifunction from the spiky morphology and massive reactive oxygen species (ROS) production. The V-Fe2 O3 can reach nearly 100 % bacterial inhibition over a long period by efficiently oxidizing the lipid membrane. Our wound disinfection results identify that the V-Fe2 O3 can not only efficiently eliminate MRSA and their biofilm but also accelerate wound recovery without causing noticeable inflammation and toxicity. This work offers essential insights into the critical roles of V-O-Fe pair sites and localized "capture and killing" in biocatalytic disinfection and provides a promising pathway for the de novo design of efficient artificial peroxidases.

Microenvironment Restruction of Emerging 2D Materials and their Roles in Therapeutic and Diagnostic Nano-Bio-Platforms.

Engineering advanced therapeutic and diagnostic nano-bio-platforms (NBPFs) have emerged as rapidly-developed pathways against a wide range of challenges in antitumor, antipathogen, tissue regeneration, bioimaging, and biosensing applications. Emerged 2D materials have attracted extensive scientific interest as fundamental building blocks or nanostructures among material scientists, chemists, biologists, and doctors due to their advantageous physicochemical and biological properties. This timely review provides a comprehensive summary of creating advanced NBPFs via emerging 2D materials (2D-NBPFs) with unique insights into the corresponding molecularly restructured microenvironments and biofunctionalities. First, it is focused on an up-to-date overview of the synthetic strategies for designing 2D-NBPFs with a cross-comparison of their advantages and disadvantages. After that, the recent key achievements are summarized in tuning the biofunctionalities of 2D-NBPFs via molecularly programmed microenvironments, including physiological stability, biocompatibility, bio-adhesiveness, specific binding to pathogens, broad-spectrum pathogen inhibitors, stimuli-responsive systems, and enzyme-mimetics. Moreover, the representative therapeutic and diagnostic applications of 2D-NBPFs are also discussed with detailed disclosure of their critical design principles and parameters. Finally, current challenges and future research directions are also discussed. Overall, this review will provide cutting-edge and multidisciplinary guidance for accelerating future developments and therapeutic/diagnostic applications of 2D-NBPFs.

Tunable Structured MXenes With Modulated Atomic Environments: A Powerful New Platform for Electrocatalytic Energy Conversion.

Owing to their rich surface chemistry, high conductivity, tunable bandgap, and thermal stability, structured 2D transition-metal carbides, nitrides, and carbonitrides (MXenes) with modulated atomic environments have emerged as efficient electrochemical energy conversion systems in the past decade. Herein, the most recent advances in the engineering of tunable structured MXenes as a powerful new platform for electrocatalytic energy conversion are comprehensively summarized. First, the state-of-the-art synthetic and processing methods, tunable nanostructures, electronic properties, and modulation principles of engineering MXene-derived nanoarchitectures are focused on. The current breakthroughs in the design of catalytic centers, atomic environments, and the corresponding structure-performance correlations, including termination engineering, heteroatom doping, defect engineering, heterojunctions, and alloying, are discussed. Furthermore, representative electrocatalytic applications of structured MXenes in energy conversion systems are also summarized. Finally, the challenges in and prospects for constructing MXene-based electrocatalytic materials are also discussed. This review provides a leading-edge understanding of the engineering of various MXene-based electrocatalysts and offers theoretical and experimental guidance for prospective studies, thereby promoting the practical applications of tunable structured MXenes in electrocatalytic energy conversion systems.

Emerging 2D Materials for Electrocatalytic Applications: Synthesis, Multifaceted Nanostructures, and Catalytic Center Design.

Currently, the development of advanced 2D nanomaterials has become an interdisciplinary subject with extensive studies due to their extraordinary physicochemical performances. Beyond graphene, the emerging 2D-material-derived electrocatalysts (2D-ECs) have aroused great attention as one of the best candidates for heterogeneous electrocatalysis. The tunable physicochemical compositions and characteristics of 2D-ECs enable rational structural engineering at the molecular/atomic levels to meet the requirements of different catalytic applications. Due to the lack of instructive and comprehensive reviews, here, the most recent advances in the nanostructure and catalytic center design and the corresponding structure-function relationships of emerging 2D-ECs are systematically summarized. First, the synthetic pathways and state-of-the-art strategies in the multifaceted structural engineering and catalytic center design of 2D-ECs to promote their electrocatalytic activities, such as size and thickness, phase and strain engineering, heterojunctions, heteroatom doping, and defect engineering, are emphasized. Then, the representative applications of 2D-ECs in electrocatalytic fields are depicted and summarized in detail. Finally, the current breakthroughs and primary challenges are highlighted and future directions to guide the perspectives for developing 2D-ECs as highly efficient electrocatalytic nanoplatforms are clarified. This review provides a comprehensive understanding to engineer 2D-ECs and may inspire many novel attempts and new catalytic applications across broad fields.

A Nanohook-Equipped Bionanocatalyst for Localized Near-Infrared-Enhanced Catalytic Bacterial Disinfection.

Novel bionanocatalysts have opened a new era in fighting multidrug-resistant (MDR) bacteria. They can kill bacteria by elevating the level of reactive oxygen species (ROS) in the presence of chemicals like H2 O2 . However, ROSs' ultrashort diffusion distance limit their bactericidal activity. We present a nanohook-equipped bionanocatalyst (Ni@Co-NC) with bacterial binding ability that shows robust ROS-generating capacity under physiological H2 O2 levels. The Ni@Co-NC's pH-dependent performance confines its effects to the biofilm microenvironment, leaving healthy tissue unaffected. Furthermore, it can generate heat upon NIR laser irradiation, enhancing its catalytic performance while achieving heat ablation against bacteria. With the Ni@Co-NC's synergistic effects, bacterial populations fall by >99.99 %. More surprisingly, the mature biofilm shows no recurrence after treatment with the Ni@Co-NC, demonstrating its tremendous potential for treating MDR bacterial related infections.

Hedgehog artificial macrophage with atomic-catalytic centers to combat Drug-resistant bacteria.

Pathogenic drug-resistant bacteria represent a threat to human health, for instance, the methicillin-resistant Staphylococcus aureus (MRSA). There is an ever-growing need to develop non-antibiotic strategies to fight bacteria without triggering drug resistance. Here, we design a hedgehog artificial macrophage with atomic-catalytic centers to combat MRSA by mimicking the "capture and killing" process of macrophages. The experimental studies and theoretical calculations reveal that the synthesized materials can efficiently capture and kill MRSA by the hedgehog topography and substantial generation of •O2- and HClO with its Fe2N6O catalytic centers. The synthesized artificial macrophage exhibits a low minimal inhibition concentration (8 µg/mL Fe-Art M with H2O2 (100 µM)) to combat MRSA and rapidly promote the healing of bacteria-infected wounds on rabbit skin. We suggest that the application of this hedgehog artificial macrophage with "capture and killing" capability and high ROS-catalytic activity will open up a promising pathway to develop antibacterial materials for bionic and non-antibiotic disinfection strategies.

Bioinspired Spiky Peroxidase-Mimics for Localized Bacterial Capture and Synergistic Catalytic Sterilization.

Besides the pandemic caused by the coronavirus outbreak, many other pathogenic microbes also pose a devastating threat to human health, for instance, pathogenic bacteria. Due to the lack of broad-spectrum antibiotics, it is urgent to develop nonantibiotic strategies to fight bacteria. Herein, inspired by the localized "capture and killing" action of bacteriophages, a virus-like peroxidase-mimic (V-POD-M) is synthesized for efficient bacterial capture (mesoporous spiky structures) and synergistic catalytic sterilization (metal-organic-framework-derived catalytic core). Experimental and theoretical calculations show that the active compound, MoO3 , can serve as a peroxo-complex-intermediate to reduce the free energy for catalyzing H2 O2 , which mainly benefits the generation of •OH radicals. The unique virus-like spikes endow the V-POD-M with fast bacterial capture and killing abilities (nearly 100% at 16 µg mL-1 ). Furthermore, the in vivo experiments show that V-POD-M possesses similar disinfection treatment and wound skin recovery efficiencies to vancomycin. It is suggested that this inexpensive, durable, and highly reactive oxygen species (ROS) catalytic active V-POD-M provides a promising broad-spectrum therapy for nonantibiotic disinfection.

Metal-Organic Framework/Ag-Based Hybrid Nanoagents for Rapid and Synergistic Bacterial Eradication.

Recent emerged metal-organic frameworks (MOFs), as superior drug carriers, provide novel strategies to combat pathogenic bacterial infections. Although various antibacterial metal ions can be easily introduced in MOFs for chemical bacterial ablation, such a single-model bactericidal method suffers from high-dose use, limited antibacterial efficiency, and slow sterilization rate. Hence, developing a dual bactericidal system is urgently required. Herein, we report an MOF/Ag-derived nanocomposite with efficient metal-ion-releasing capability and robust photo-to-thermal conversion effect for synergistic sterilization. The MOF-derived nanocarbon consisting of metallic zinc and a graphitic-like carbon framework is first synthesized, and then Ag nanoparticles (AgNPs) are evenly introduced via the displacement reaction between Zn and Ag+. Upon near-infrared irradiation, the fabricated nanoagents can generate massive heat to destroy bacterial membranes. Meanwhile, abundant Zn2+ and Ag+ ions are released to make chemical damage to bacterial intracellular substances. Systematic antibacterial experiments reveal that such dual-antibacterial effort can endow the nanoagents with nearly 100% bactericidal ratio for highly concentrated bacteria at a very low dosage (0.16 mg/mL). Furthermore, the nanoagents exhibit less cytotoxicity, which provides potential possibilities for the applications in the biological field. In vivo assessment indicates that the nanocomposites can realize rapid and safe wound sterilization and are expected to be an alternative to antibiotics. Overall, we present an easily fabricated structure-engineered nanocomposite with chemical and photothermal effects for broad-spectrum bacterial sterilization.

Methylation of Phospholipase A2 Group VII Gene Is Associated with Brain Arteriovenous Malformations in Han Chinese Populations.

The purpose of this study was to evaluate the contribution of DNA methylation at the phospholipase A2 group VII (PLA2G7) gene, to the risk of developing brain arteriovenous malformations (BAVMs) and intracranial aneurysms (IAs) in a Han Chinese population. Seventy patients with BAVMs or IAs and 26 control subjects were recruited to evaluate PLA2G7 methylation by bisulfite pyrosequencing. CpG3 methylation at the PLA2G7 was significantly higher in BAVM patients than in the control group (Chr6,46735560, p = 0.042). Gender subgroup analysis showed that PLA2G7 CpG4 (Chr6,46735574, p = 0.033) and mean methylation (p = 0.037) levels were significantly associated with BAVM in males. However, in females, PLA2G7 methylations were much lower in IAs than in controls [CpG2 (Chr6,46735558), p = 0.030] and BAVMs [CpG2, p = 0.001; CpG4, p = 0.007; CpG6 (Chr6, 46735579), p = 0.024; mean, p = 0.013]. In addition, mean methylation of the PLA2G7 significantly correlated with apoB levels in all individuals (r = 0.288, p = 0.006), and with apoE in BAVM patients (r = 0.259, p = 0.016). The receiver operating characteristic (ROC) curve showed that PLA2G7 CpG3 methylation might be a predictor of BAVM risk in Han Chinese (area under curve (AUC) = 0.76, p = 0.008). PLA2G7 DNA methylation was significantly associated with the risk of developing BAVMs in males or IAs in females. Future studies on the PLA2G7 mechanisms should be performed on the pathogenesis of these cerebrovascular disorders.

Construction of Kevlar nanofiber/graphene oxide composite beads as safe, self-anticoagulant, and highly efficient hemoperfusion adsorbents.

Recently emerged hemoperfusion absorbents, e.g. ion-exchange resin, activated carbon, and other porous materials, provide numerous novel possibilities to cure chronic liver failure (CLF) and renal failure (CRF). However, the limited adsorption performance and unsatisfactory blood compatibility significantly impede the development of the absorbents. Hence, designing safe and self-anticoagulant hemoperfusion absorbents with robust toxin clearance remains a considerable challenge. Here, brand new Kevlar-based composite gel beads for hemoperfusion are prepared by interface assembly based on π-π interaction. First, Kevlar nanofiber-graphene oxide (K-GO) beads are produced by liquid-liquid phase separation. Then, sodium p-styrenesulfonate (SS) is adsorbed onto the K-GO interface by π-π interaction and initiated to achieve the composite gel (K-GO/PSS) beads with an interfacial crosslinked structure. Such composite gel beads possess superior mechanical strength and self-anticoagulation capability, owing to the dual-network structure and heparin-mimicking gel structure, respectively. Furthermore, the K-GO/PSS beads show robust adsorption capacities for different kinds of toxins due to their strong charge and π-π interactions. A simulated hemoperfusion experiment in vitro demonstrates that the concentrations of the toxins in the blood can be restored to normal values within 30 minutes. In general, we envision that such composite gel beads will provide new strategies for future clinical CLF and CRF treatments.

Significant Association of CXCL12 rs1746048 with LDL-C Level in Intracranial Aneurysms.

BACKGROUND: C-X-C motif chemokine ligand 12 (CXCL12) may play an important role in the development of Intracranial Aneurysm (IA). OBJECTIVE: The goal of this study was to explore the association between CXCL12 rs1746048 genotypes and circulating lipid concentrations along with the risk of IA. METHODS: A total of 256 IA patients and 361 healthy volunteers were included in the case-control study. The genotypes of CXCL12 rs1746048 were detected by Melting Temperature shift (Tmshift) Polymerase Chain Reaction (PCR). RESULTS: Significant higher levels were seen in Total Cholesterol (TC) (padjusted < 0.001), Highdensity Lipoprotein Cholesterol (HDL-C) (padjusted < 0.001), Low-density Lipoprotein Cholesterol (LDL-C) (padjusted < 0.001), Apolipoprotein A-I (ApoA-I) (padjusted = 0.040), and Apolipoprotein B (ApoB) (padjusted < 0.001) in IAs compared with controls. CXCL12 rs1746048 T allele frequency showed significant association with the risk of IA in the female group aged 65 or above (p = 0.019, Odds Ratio (OR) = 2.15, 95% confidence interval (95%CI) = 1.13 - 4.11, power = 64.8%). Moreover, CXCL12 rs1746048 was likely to be a risk variant of IA under the recessive model in females older than 65 years. (p = 0.030, OR = 3.77, 95%CI = 1.08 - 13.12, power = 81.8%). Additionally, we also found that the levels of LDL-C were significantly different among three genotypes (CC vs. CT vs. TT = 2.75±0.73 vs. 3.03±0.89 vs. 2.82±0.72, p = 0.035) in IA patients. CONCLUSION: Our results suggest that CXCL12 rs1746048 is significantly associated with IA risk in Han Chinese females aged 65 years and older. Additionally, the genotypes of CXCL12 rs1746048 may affect the LDL-C concentrations in IA patients.

Association of CDKN2B-AS1 rs1333049 with Brain Diseases: A Case-control Study and a Meta-analysis.

OBJECTIVE: CDKN2B-AS1 polymorphisms were shown to associate with the risk of stroke in European. The goal of this study was to evaluate the contribution of CDKN2B-AS1 rs1333049 to the risk of hemorrhagic stroke (HS) and brain tumor (BT) in Han Chinese. METHODS: A total of 142 HSs, 115 BTs, and 494 controls were included in the current association study. The genotyping test was performed using the melting temperature shift method. RESULTS: We failed to validate the association of CDKN2B-AS1 rs1333049 with the risk of brain disease. Significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p=0.027), high-density lipoprotein cholesterol (HDL-C) (p＜0.001) and total cholesterol (TC) (p＜0.001) were found in HSs in the genotype GG/GC carriers, but not the genotype CC carriers (p＞0.05). The meta-analysis of 10 studies among 133,993 individuals concluded that rs1333049 of CDKN2B-AS1 gene was likely to increase a 16% incidence rate of cerebrovascular disease (CD) among various populations (odds ratio 1.16, 95% confidence interval 1.08-1.25; p＜0.0001, random-effect method). CONCLUSION: Our case-control study identified rs1333049 genotypes showed different association with the concentration of the LDL-C, HDL-C and TC in the HS patients. Meta-analysis supported the association between rs1333049 and CD risk in various populations, although we were unable to observe association between rs1333049 and the risk of HSs in Han Chinese.