Regulating zinc ion transport behavior and solvated structure towards stable aqueous Zn metal batteries

Aqueous Zn metal batteries(AZMBs)with intrinsic safety,high energy density and low cost have been regarded as promising electrochemical energy storage devices.However,the parasitic reaction on metallic Zn anode and the incompatibility between electrode and electrolytes lead to the deterioration of electrochemical performance of AZMBs during the cycling.The critical point to achieve the stable cycling of AZMBs is to properly regulate the zinc ion solvated structure and transfer behavior between metallic Zn anode and electrolyte.In recent years,numerous achievements have been made to resolve the formation of Zn dendrite and interface incompatible issues faced by AZMBs via optimizing the sheath structure and transport capability of zinc ions at electrode-electrolyte interface.In this review,the challenges for metallic Zn anode and electrode-electrolyte interface in AZMBs including dendrite formation and interface characteristics are presented.Following the influences of different strategies involving designing advanced electrode structu re,artificial solid electrolyte interphase(SEI)on Zn anode and electrolyte engineering to regulate zinc ion solvated sheath structure and transport behavior are summarized and discussed.Finally,the perspectives for the future development of design strategies for dendrite-free Zn metal anode and long lifespan AZMBs are also given.

Bioinspired metal-organic framework nanozyme reinforced with thermosensitive hydrogel for regulating inflammatory responses in Parkinson’s disease

Parkinson’s disease(PD)is a prevalent neurodegenerative disorder accompanied by movement disorders and neuroinflammatory injury.Anti-inflammatory intervention to regulate oxidative stress in the brain is beneficial for managing PD.However,traditional natural antioxidants have failed to meet the clinical treatment demands due to insufficient activity and sustainability.Herein,Cu-doping zeolite imidazolate framework-8(ZIF-8)nanozyme is designed to simulate Cu/Zn superoxide dismutase(SOD)by biomimetic mineralization.The nanozyme composite is then integrated into thermosensitive hydrogel(poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid)(PLGA-PEG-PLGA))to form an effective antioxidant system(Cu-ZIF@Hydrogel).The thermosensitive hydrogel incorporating nanozymes demonstrate distinct viscoelastic properties aimed at enhancing local nanozyme adhesion,prolonging nanozyme retention time,and modulating antioxidant activity,thus significantly improving the bioavailability of nanozymes.At the cellular and animal levels of PD,we find that Cu-ZIF@Hydrogel bypass the blood-brain barrier and efficiently accumulate in the nerve cells.Moreover,the Cu-ZIF@Hydrogel significantly alleviate the PD’s behavioral and pathological symptoms by reducing the neuroinflammatory levels in the lesion site.Therefore,the hydrogel-incorporating nanozyme system holds great potential as a simple and reliable avenue for managing PD.

Corrigendum to“Mussel-inspired nanozyme catalyzed conductive and self-setting hydrogel for adhesive and antibacterial bioelectronics”[Bioact.Mater.6(2021)2676-2687/452]

The authors regret<that the published version of the above article contained an error in Figure 5d,which was not identified during the proofing stage.The Figure 5d has been revised as follow.The authors would like to apologise for any inconvenience caused and state that the correction does not change the scientific conclusions of the article in any way.

Erratum to:CD146 as a promising therapeutic target for retinal and choroidal neovascularization diseases

Erratum to:Sci China Life Sciences,Volume 65,Issue 6:1157-1170(2022),https://doi.org/10.1007/s11427-021-2020-0This paper contains four errors in Figure 4 and Figure 5.In Figure 4C,the image labeled as"1%O_(2)+IgG ctrl"is incorect.This image is another one for 1%O_(2) group.We provide a new image as follows for 1%O_(2)+IgG ctrl group.This new image does not affect the conclusion of this article.

Nanozyme:A promising tool from clinical diagnosis and environmental monitoring to wastewater treatment

Natural enzymes,owing to their outstanding catalytic efficiency and substrate specificity,have been used in a variety of applications including clinical diagnosis,environmental monitoring and wastewater treatment.However,they face inevitable problems such as relatively high cost and lack of stability,dramatically hindering their practical applications in the industry.Recently,a class of nanomaterial that possesses intrinsic enzyme-like properties,nanozyme,has emerged exhibiting numerous advantages over its natural counterpart and has been used as a viable enzyme alternative.In the past decade there are many reviews on nanozyme.The previous discussions tend to view nanozyme as a type of nanomaterial rather than an enzyme.However,it is the enzyme-like activity of nanozymes that provides foundation for their application and nanozymes with the same enzymatic activity usually have some regularity in application.Herein,in this review,we attempt to classify nanozymes by their enzyme-like activity to explain the application principle and relevant cases of nanozymes in clinical diagnosis,environmental monitoring and wastewater treatment,expecting to promote deeper thinking of nanozymes as enzyme mimics and provide useful guidance for future research.

Mussel-inspired nanozyme catalyzed conductive and self-setting hydrogel for adhesive and antibacterial bioelectronics

Adhesive hydrogels have broad applications ranging from tissue engineering to bioelectronics;however,fabricating adhesive hydrogels with multiple functions remains a challenge.In this study,a mussel-inspired tannic acid chelated-Ag(TA-Ag)nanozyme with peroxidase(POD)-like activity was designed by the in situ reduction of ultrasmall Ag nanoparticles(NPs)with TA.The ultrasmall TA-Ag nanozyme exhibited high catalytic activity to induce hydrogel self-setting without external aid.The nanozyme retained abundant phenolic hydroxyl groups and maintained the dynamic redox balance of phenol-quinone,providing the hydrogels with long-term and repeatable adhesiveness,similar to the adhesion of mussels.The phenolic hydroxyl groups also afforded uniform distribution of the nanozyme in the hydrogel network,thereby improving its mechanical properties and conductivity.Furthermore,the nanozyme endowed the hydrogel with antibacterial activity through synergistic effects of the reactive oxygen species generated via POD-like catalytic reactions and the intrinsic bactericidal activity of Ag.Owing to these advantages,the ultrasmall TA-Ag nanozyme-catalyzed hydrogel could be effectively used as an adhesive,antibacterial,and implantable bioelectrode to detect bio-signals,and as a wound dressing to accelerate tissue regeneration while preventing infection.Therefore,this study provides a promising approach for the fabrication of adhesive hydrogel bioelectronics with multiple functions via mussel-inspired nanozyme catalysis.

Nanozymes Inspired by Natural Enzymes

CONSPECTUS:Nanozymes,nanomaterials with enzyme-like activities with high structural stability,adjustable catalytic activity,functional diversity,recyclability,and feasibility in large-scale preparation,have become a hot spot in the field of artificial enzymes in recent years and are expected to become potential surrogates and competitors for natural enzymes in practical applications.With the development of in-depth research and a wide range of application requirements,creating nanozymes with catalytic performance comparable to or even surpassing that of natural enzymes has been the key research topic in this field.Most of the nanozymes reported in the past were obtained based on random synthesis and screening,for which the catalytic efficiency is far inferior to that of natural enzymes.Natural enzymes that have evolved over hundreds of millions of years have developed a lot of high-efficiency catalysis know-how hidden in their structural features.To create highly active nanozymes,we assumed that there is a general structure−activity relationship between nanozymes and natural enzymes and proposed the nanozyme optimization strategy by grafting the catalytic principles of natural enzymes into the rational design of nanozymes.On the basis of this bioinspired strategy,a series of nanozymes that exhibit similar catalytic activities that are closer to or even beyond those of natural enzymes have been successfully synthesized.By now,rationally designed high-activity bioinspired nanozymes have become a hot topic in the current research on nanozymes.In this Account,we focus on recent representative research progress in the systemic design and construction of bioinspired nanozymes and are devoted to introducing strategic concepts in the bioinspired optimization of nanozymes.We show that the de novo design of nanozymes by simulating the amino acid microenvironment and using metal-free architecture and the coordination structure of metal active sites in natural enzymes is an effective strategy for significantly improving the catalytic performance of nanozymes.A future perspective of the challenges and countermeasures of bioinspired nanozymes is proposed on the basis of these achievements.We hope that the biologically inspired perception will arouse widespread interest in fundamental research and practical applications as well as provide inspiration for the rational design of nanozymes.

Engineering Multifunctional Thylakoid as an Oxygen Self-Supplying Photosensitizer for Esophageal Squamous Cell Carcinoma-Targeted Photodynamic Therapy

Photodynamic therapy(PDT)has emerged as an alternative treatment strategy for esophageal squamous cell carcinoma(ESCC).However,the clinical therapeutic efficiency of PDT is severely limited by poorly targeted photosensitizer delivery,insufficient oxygen supply,and neutralization by excessive glutathione(GSH)in tumor tissue.Herein,an engineered multifunctional thylakoid nanostructure,TMEM@PLGA@GA(abbreviated as TEPG),composed of a thylakoid membrane(TM)and ESCC cell membrane(EM)-fused biomembrane(TM-EM)shell and gambogic acid(GA)-loaded poly(lactic-co-glycolic acid)nanocore,was designed for enhanced PDT for ESCC.When fused with EM,TM-EM exhibits a tumor targeting advantage due to the homologous affinity of tumor membrane camouflage.The catalase present on TM-EM catalytically decomposes endogenous hydrogen peroxide into oxygen to alleviate hypoxia in the tumor tissue.Moreover,when TEPG was selectively internalized by ESCC cells,GA was released to consume the excessive intracellular GSH.Under infrared irradiation,the PDT effects were enhanced by the self-oxygen supply and GSH scavenging ability provided by TEPG.An in vivo study showed that TEPG effectively induced ESCC tumor cell apoptosis and greatly inhibited the growth of ESCC tumors under infrared irradiation.This study constructed an engineered multifunctional thylakoid-based nanomedicine as an integrated solution to enhance PDT for ESCC.

Metastable Iron Sulfides: A Versatile Antibacterial Candidate with Multiple Mechanisms against Bacterial Resistance

Bacterial infections pose an ongoing threat to global human health,an issue of growing urgency due to the emergence of resistance against many currently available antibiotics.Recently,the World Health Organization(WHO)launched a global appeal for the development of novel antibiotics to combat this issue.Ideal antibiotics should possess specific antibacterial effects,without causing resistance.However,the discovery of different antibiotics is lagging the development of drug-resistant bacteria.Many newly developed antibiotics not only are rapidly resisted by bacteria but also are ineffective against persistent bacteria embedded in biofilms and host cells.To tackle these challenges,innovative concepts and approaches are required for the discovery of novel antibacterial candidates.Agents for use against pathogenic bacteria were developed long before the discovery of antibiotics.For 3000 years,garlic has been considered an efficient antibacterial compound,utilized to prevent and treat bacterial infection worldwide,although the specific mechanisms remain unclear.Modern research shows that sulfur-containing chemicals are the primary active constituents of garlic and play key roles in its inherent antimicrobial activity,such as diallyl disulfide(DADS)and diallyl trisulfide(DATS).In contrast,inorganic sulfides for antibacterial use have not been deeply studied.It has been well-known that iron sulfides are an essential part of the geochemical and biological sulfur cycles.Both stable and metastable iron sulfides can be formed under abiotic sediment conditions and biotic process.In particular,certain bacteria species growth need iron sulfide as nutrient source or produce iron sulfide.In addition,iron sulfur clusters as special metastable iron sulfide take part in many important metabolic pathways in most organisms.These physicochemical and biological properties inspire us that iron sulfides are a type of valuable material for investigation and utilization.Below we will introduce a new antibacterial candidate based on iron sulfides,which kill bacteria via multiple mechanisms of action(MoAs).We will first discuss the types of iron sulfides with inherent antibacterial activity,i.e.,metastable species that can release iron ions and polysulfides in aqua.The intrinsic properties of iron sulfides and released iron and polysulfides are analyzed in regard to antibacterial effects under different physiological conditions.In particular,ferrous ion−polysulfide synergized ferroptosis-like death is proposed to kill bacteria with broad spectrum and selectivity.In addition,the versatile MoAs enable metastable iron sulfides(mFeSs)to kill resistant bacteria,eradicate biofilms,and suppress intracellular persistent species without causing new drug resistance.Importantly,the efficient antibacterial properties have been validated in animal models bearing infections including wounds,pneumonia,caries,and bacterial vaginosis,demonstrating great translational potential.Lastly,we will summarize the challenges of iron sulfides,proposing a possible development direction in the future.Our studies on iron sulfides can serve as a paradigm for the design and discovery of antibacterial nanomaterials,which may contribute for the war against drug-resistant pathogenic bacteria.

CD146 as a promising therapeutic target for retinal and choroidal neovascularization diseases

Blood vessel dysfunction causes several retinal diseases,including diabetic retinopathy,familial exudative vitreoretinopathy,macular degeneration and choroidal neovascularization in pathological myopia.Vascular endothelial growth factor(VEGF)-neutralizing proteins provide benefits in most of those diseases,yet unsolved haemorrhage and frequent intraocular injections still bothered patients.Here,we identified endothelial CD146 as a new target for retinal diseases.CD146 expression was activated in two ocular pathological angiogenesis models,a laser-induced choroid neovascularization model and an oxygeninduced retinopathy model.The absence of CD146 impaired hypoxia-induced cell migration and angiogenesis both in cell lines and animal model.Preventive or therapeutic treatment with anti-CD146 antibody AA98 significantly inhibited hypoxia-induced aberrant retinal angiogenesis in two retinal disease models.Mechanistically,under hypoxia condition,CD146 was involved in the activation of NFκB,Erk and Akt signalling pathways,which are partially independent of VEGF.Consistently,anti-CD146therapy combined with anti-VEGF therapy showed enhanced impairment effect of hypoxia-induced angiogenesis in vitro and in vivo.Given the critical role of abnormal angiogenesis in retinal and choroidal diseases,our results provide novel insights into combinatorial therapy for neovascular fundus diseases.

CD146,from a melanoma cell adhesion molecule to a signaling receptor

CD146 was originally identified as a melanoma cell adhesion molecule(MCAM)and highly expressed in many tumors and endothelial cells.However,the evidence that CD146 acts as an adhesion molecule to mediate a homophilic adhesion through the direct interactions between CD146 and itself is still lacking.Recent evidence revealed that CD146 is not merely an adhesion molecule,but also a cellular surface receptor of miscellaneous ligands,including some growth factors and extracellular matrixes.Through the bidirectional interactions with its ligands,CD146 is actively involved in numerous physiological and pathological processes of cells.Overexpression of CD146 can be observed in most of malignancies and is implicated in nearly every step of the development and progression of cancers,especially vascular and lymphatic metastasis.Thus,immunotherapy against CD146 would provide a promising strategy to inhibit metastasis,which accounts for the majority of cancer-associated deaths.Therefore,to deepen the understanding of CD146,we review the reports describing the newly identified ligands of CD146 and discuss the implications of these findings in establishing novel strategies for cancer therapy.

Ferritin nanocages for early theranostics of tumors via inflammation-enhanced active targeting

Engineered nanocarriers have been widely developed for tumor theranostics.However,the delivery of imaging probes or therapeutic drugs to the tumor pre-formation site for early and accurate detection and therapy remains a major challenge.Here,by using tailor-functionalized human H-ferritin(HFn),we developed a triple-modality nanoprobe IRdye800-M-HFn and achieved the early imaging of tumor cells before the formation of solid tumor tissues.Then,we developed an HFn-doxorubicin(Dox)drug delivery system by loading Dox into the HFn protein cage and achieved early-stage tumor therapy.The intravenous injection of HFn nanoprobes enabled the imaging of tumor cells as early as two days after tumor implantation,and the triple-modality imaging techniques,namely,near-infrared fluorescence molecular imaging(NIR-FMI),magnetic resonance imaging(MRI),and photoacoustic imaging(PAI),ensured the accuracy of detection.Further exploration indicated that HFn could specifically penetrate into pre-solid tumor sites by tumor-associated inflammation-mediated blood vessel leakage,followed by effective accumulation in tumor cells by the specific targeting property of HFn to transferrin receptor 1.Thus,the HFn-Dox drug delivery system delivered Dox into the tumor pre-formation site and effectively killed tumor cells at early stage.IRDye800-M-HFn nanoprobes and HFn-Dox provide promising strategies for early-stage tumor diagnosis and constructive implications for early-stage tumor treatment.