ROS Balance Autoregulating Core-Shell CeO_(2)@ZIF-8/Au Nanoplatform for Wound Repair

Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.

Dual‑Atom Nanozyme Eye Drops Attenuate Inflammation and Break the Vicious Cycle in Dry Eye Disease

Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Although inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROS)play a pivotal role in the vicious cycle by regulating inflammation from upstream.Therefore,current therapies merely targeting inflammation show the failure of DED treatment.Here,a novel dual-atom nanozymes(DAN)-based eye drops are developed.The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer.The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell apoptosis.Consequently,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious cycle.Our findings open an avenue to make the DAN as an intervention form to DED and ROSmediated inflammatory diseases.

Intelligent Vascularized 3D/4D/5D/6D‑Printed Tissue Scaffolds

Blood vessels are essential for nutrient and oxygen delivery and waste removal.Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering.Additive manufacturing is a manufacturing technology that creates three-dimensional solids by stacking substances layer by layer,mainly including but not limited to 3D printing,but also 4D printing,5D printing and 6D printing.It can be effectively combined with vascularization to meet the needs of vascularized tissue scaffolds by precisely tuning the mechanical structure and biological properties of smart vascular scaffolds.Herein,the development of neovascularization to vascularization to bone tissue engineering is systematically discussed in terms of the importance of vascularization to the tissue.Additionally,the research progress and future prospects of vascularized 3D printed scaffold materials are highlighted and presented in four categories:functional vascularized 3D printed scaffolds,cell-based vascularized 3D printed scaffolds,vascularized 3D printed scaffolds loaded with specific carriers and bionic vascularized 3D printed scaffolds.Finally,a brief review of vascularized additive manufacturing-tissue scaffolds in related tissues such as the vascular tissue engineering,cardiovascular system,skeletal muscle,soft tissue and a discussion of the challenges and development efforts leading to significant advances in intelligent vascularized tissue regeneration is presented.

Bioresource Upgrade for Sustainable Energy,Environment,and Biomedicine

We conceptualize bioresource upgrade for sustainable energy,environment,and biomedicine with a focus on circular economy,sustainability,and carbon neutrality using high availability and low utilization biomass(HALUB).We acme energy-efficient technologies for sustainable energy and material recovery and applications.The technologies of thermochemical conversion(TC),biochemical conversion(BC),electrochemical conversion(EC),and photochemical conversion(PTC)are summarized for HALUB.Microalgal biomass could contribute to a biofuel HHV of 35.72 MJ Kg^(-1)and total benefit of 749$/ton biomass via TC.Specific surface area of biochar reached 3000 m^(2)g^(-1)via pyrolytic carbonization of waste bean dregs.Lignocellulosic biomass can be effectively converted into bio-stimulants and biofertilizers via BC with a high conversion efficiency of more than 90%.Besides,lignocellulosic biomass can contribute to a current density of 672 mA m^(-2)via EC.Bioresource can be 100%selectively synthesized via electrocatalysis through EC and PTC.Machine learning,techno-economic analysis,and life cycle analysis are essential to various upgrading approaches of HALUB.Sustainable biomaterials,sustainable living materials and technologies for biomedical and multifunctional applications like nano-catalysis,microfluidic and micro/nanomotors beyond are also highlighted.New techniques and systems for the complete conversion and utilization of HALUB for new energy and materials are further discussed.

Split-Ring Structured All-Inorganic Perovskite Photodetector Arrays for Masterly Internet of Things

Photodetectors with long detection distances and fast response are important media in constructing a non-contact human-machine interface for the Masterly Internet of Things(MIT).All-inorganic perovskites have excellent optoelectronic performance with high moisture and oxygen resistance,making them one of the promising candidates for high-performance photodetectors,but a simple,low-cost and reliable fabrication technology is urgently needed.Here,a dual-function laser etching method is developed to complete both the lyophilic split-ring structure and electrode patterning.This novel split-ring structure can capture the perovskite precursor droplet efficiently and achieve the uniform and compact deposition of CsPbBr3 films.Furthermore,our devices based on laterally conducting split-ring structured photodetectors possess outstanding performance,including the maximum responsivity of 1.44×105 mA W^(−1),a response time of 150μs in 1.5 kHz and one-unit area<4×10-2 mm2.Based on these split-ring photodetector arrays,we realized three-dimensional gesture detection with up to 100 mm distance detection and up to 600 mm s^(−1) speed detection,for low-cost,integrative,and non-contact human-machine interfaces.Finally,we applied this MIT to wearable and flexible digital gesture recognition watch panel,safe and comfortable central controller integrated on the car screen,and remote control of the robot,demonstrating the broad potential applications.

Chip-Based High-Dimensional Optical Neural Network

Parallel multi-thread processing in advanced intelligent processors is the core to realize high-speed and high-capacity signal processing systems.Optical neural network(ONN)has the native advantages of high parallelization,large bandwidth,and low power consumption to meet the demand of big data.Here,we demonstrate the dual-layer ONN with Mach-Zehnder interferometer(MZI)network and nonlinear layer,while the nonlinear activation function is achieved by optical-electronic signal conversion.Two frequency components from the microcomb source carrying digit datasets are simultaneously imposed and intelligently recognized through the ONN.We successfully achieve the digit classification of different frequency components by demultiplexing the output signal and testing power distribution.Efficient parallelization feasibility with wavelength division multiplexing is demonstrated in our high-dimensional ONN.This work provides a high-performance architecture for future parallel high-capacity optical analog computing.

From Bench to the Clinic: The Path to Translation of Nanotechnology-Enabled mRNA SARS-CoV-2 Vaccines

During the last decades,the use of nanotechnology in med icine has effectively been translated to the design of drug delivery systems,nanostructured tissues,diagnostic platforms,and novel nanomaterials against several human diseases and infectious pathogens.Nanotechnology-enabled vaccines have been positioned as solutions to mitigate the pandemic outbreak caused by the novel pathogen severe acute respiratory syndrome coronavirus 2.To fast-track the development of vaccines,unprecedented industrial and academic collaborations emerged around the world,resulting in the clinical translation of effective vaccines in less than one year.In this article,we provide an overview of the path to translation from the bench to the clinic of nanotechnology-enabled messenger ribonucleic acid vaccines and examine in detail the types of delivery systems used,their mechanisms of action,obtained results during each phase of their clinical development and their regulatory approval process.We also analyze how nanotechnology is impacting global health and economy during the COVID-19 pandemic and beyond.

One-Step Preparation of Green Fabric for Continuous Antibacterial Applications

Polypropylene(PP)scaffolds are the most commonly used biomedical scaffolds despite their disadvan-tages,which include problems with adhesion,infection,and inflammatory responses.Here,we report on the successful development of a facile one-step method to fabricate a series of novel triclosan poly-dopamine polypropylene(TPP)composite scaffolds and thereby effectively improve the biocompatibility and long-term antibacterial properties of PP scaffolds.The antibacterial triclosan can effectively interact with dopamine during biocompatible polydopamine formation on the PP scaffold by one-step green fab-rication.Thanks to the sustained release of triclosan from the biocompatible polydopamine coating,a 5mm×5mm sample of TPP-coated scaffold made with a triclosan concentration of 8 mg-mL^(-1)(referredto herein as TPP-8)exhibited a continuous antibacterial effect against both Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)for more than 15d,at maximum antibacterial volumes of 2 and 5mL,respectively.Our study establishes a new direction for facile long-term antibacterial studies for medical applications.

Nanoengineered Shear-Thinning Hydrogel Barrier for Preventing Postoperative Abdominal Adhesions

More than 90%of surgical patients develop postoper-ative adhesions,and the incidence of hospital re-admissions can be as high as 20%.Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive interventions.To solve thisclinical limitation,we developed an injectable and sprayable shear-thinning hydrogel barrier(STHB)composed of silicate nanoplatelets and poly(ethylene oxide).We optimized this technology to recover mechanical integrity after stress,enabling its delivery though inject-able and sprayable methods.We also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in vitro.The STHB was then tested in a rodent model of peritoneal injury to determine its e cacy preventing the formation of postoperative adhesions.After two weeks,the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions,and STHB formulations presented superior e cacy compared to a commercially available adhesion barrier.Histological and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB formulations.Our technology demonstrated increased e cacy,ease of use in complex anatomies,and compatibility with di erent delivery methods,providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions.

Targeting Hypoxic Tumors with Hybrid Nanobullets for Oxygen-Independent Synergistic Photothermal and Thermodynamic Therapy

Hypoxia is a feature of solid tumors and it hinders the therapeutic efficacy of oxygen-dependent cancer treatment.Herein,we have developed all-organic oxygen-independent hybrid nanobullets ZPA@HA-ACVA-AZ for the“precise strike”of hypoxic tumors through the dual-targeting effects from surface-modified hyaluronic acid(HA)and hypoxia-dependent factor carbonic anhydrase IX(CA IX)-inhibitor acetazolamide(AZ).The core of nanobullets is the special zinc(II)phthalocyanine aggregates(ZPA)which could heat the tumor tissues upon 808-nm laser irradiation for photothermal therapy(PTT),along with the alkyl chain-functionalized thermally decomposable radical initiator ACVA-HDA on the side chain of HA for providing oxygen-independent alkyl radicals for ablating hypoxic cancer cells by thermodynamic therapy(TDT).The results provide important evidence that the combination of reverse hypoxia hallmarks CA IX as targets for inhibition by AZ and synergistic PTT/TDT possess incomparable therapeutic advantages over traditional(reactive oxygen species(ROS)-mediated)cancer treatment for suppressing the growth of both hypoxic tumors and their metastasis.

Sorting Gold and Sand(Silica) Using Atomic Force Microscope-Based Dielectrophoresis

Additive manufacturing-also known as 3D printing-has attracted much attention in recent years as a powerful method for the simple and versatile fabrication of complicated three-dimensional structures.However,the current technology still exhibits a limitation in realizing the selective deposition and sorting of various materials contained in the same reservoir,which can contribute significantly to additive printing or manufacturing by enabling simultaneous sorting and deposition of different substances through a single nozzle.Here,we propose a dielectrophoresis(DEP)-based material-selective deposition and sorting technique using a pipette-based quartz tuning fork(QTF)-atomic force microscope(AFM) platform DEPQA and demonstrate multi-material sorting through a single nozzle in ambient conditions.We used Au and silica nanoparticles for sorting and obtained 95% accuracy for spatial separation,which confirmed the surfaceenhanced Raman spectroscopy(SERS).To validate the scheme,we also performed a simulation for the system and found qualitative agreement with the experimental results.The method that combines DEP,pipette-based AFM,and SERS may widely expand the unique capabilities of 3D printing and nano-micro patterning for multi-material patterning,materials sorting,and diverse advanced applications.

Functional Surfactants for Molecular Fishing,Capsule Creation,and Single-Cell Gene Expression

Creating a single surfactant that is open to manipulation,while maintaining its surface activity,robustness,and compatibility,to expand the landscape of surfactant-dependent assays is extremely challenging.We report an oxidation-responsive precursor with thioethers and multiple 1,2-diols for creating a variety of functional surfactants from one parent surfactant.Using these multifunctional surfactants,we stabilize microfluidics-generated aqueous droplets.The droplets encapsulate different components and immerse in a bioinert oil with distinct interfaces where an azide-bearing surfactant allow fishing of biomolecules from the droplets,aldehyde-bearing surfactant allow fabrication of microcapsules,and hydroxyl-bearing surfactants,with/without oxidized thioethers,allow monitoring of single-cell gene expression.Creating multifunctional surfactants poses opportunities for broad applications,including adsorption,bioanalytics,catalysis,formulations,coatings,and programmable subset of emulsions.

Mitochondrial H_(2)S_(n)-Mediated Anti-Inflammatory Theranostics

The insistent demand for space-controllable delivery,which reduces the side effects of non-steroidal antiinflammatory drugs(NSAIDs),has led to the development of a new theranostics-based approach for anti-inflammatory therapy.The current anti-inflammatory treatments can be improved by designing a drug delivery system responsive to the inflammatory site biomarker,hydrogen polysulfide(H_(2)S_(n)).Here,we report a noveltheranostic agent 1(TA1),consisting of three parts:H_(2)S_(n)-mediated triggering part,a two-photon fluorophore bearing mitochondria targeting unit(Rhodol-TPP),and anti-inflammatory COX inhibitor(indomethacin).In vitro experiments showed that TA1 selectively reacts with H_(2)S_(n)to concomitantly release both Rhodol-TPP and indomethacin.Confocal-microscopy imaging of inflammation-inducedlive cells suggested that TA1 is localized in the mitochondria where the H_(2)S_(n)is overexpressed.The TA1 reacted with H_(2)S_(n)in the endogenous and exogenous H_(2)S_(n)environments and in lipopolysaccharide treated inflammatory cells.Moreover,TA1 suppressed COX-2 level in the inflammatory-induced cells and prostaglandin E 2(PGE2)level in blood serum from inflammation-induced mouse models.In vivo experiments with inflammation-induced mouse models suggested that TA1 exhibits inflammation-site-elective drug release followed by significant therapeutic e ects,showing its function as a theranostic agent,capable of both anti-inflammatory therapy and precise diagnosis.Theranostic behavior of TA1 is highly applicable in vivo model therapeutics for the inflammatory disease.

Microsnoop: A generalist tool for microscopy image representation

Accurate profiling of microscopy images from small scale to high throughput is an essential procedure in basic and applied biological research.Here,we present Microsnoop,a novel deep learning–based representation tool trained on large-scale microscopy images using masked self-supervised learning.Microsnoop can process various complex and heterogeneous images,and we classified images into three categories:single-cell,full-field,and batch-experiment images.Our benchmark study on 10 high-quality evaluation datasets,containing over 2,230,000 images,demonstrated Microsnoop’s robust and state-ofthe-art microscopy image representation ability,surpassing existing generalist and even several custom algorithms.Microsnoop can be integrated with other pipelines to perform tasks such as superresolution histopathology image and multimodal analysis.Furthermore,Microsnoop can be adapted to various hardware and can be easily deployed on local or cloud computing platforms.We will regularly retrain and reevaluate the model using communitycontributed data to consistently improve Microsnoop.

Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries

Central nervous system(CNS)injuries,including stroke,traumatic brain injury,and spinal cord injury,are essential causes of death and long-term disability and are difficult to cure,mainly due to the limited neuron regeneration and the glial scar formation.Herein,we apply extracellular vesicles(EVs)secreted by M2 microglia to improve the differentiation of neural stem cells(NSCs)at the injured site,and simultaneously modify them with the injured vascular targeting peptide(DA7R)and the stem cell recruiting factor(SDF-1)on their surface via copper-free click chemistry to recruit NSCs,inducing their neuronal differentiation,and serving as the nanocarriers at the injured site(Dual-EV).Results prove that the Dual-EV could target human umbilical vascular endothelial cells(HUVECs),recruit NSCs,and promote the neuronal differentiation of NSCs in vitro.Furthermore,10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis,and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs,miR30b-3p,miR-222-3p,miR-129-5p,and miR-155-5p may exert effect of inducing NSC to differentiate into neurons.In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice,potentiate NSCs recruitment,and increase neurogenesis.This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells,and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Lipid nanomaterials-based RNA therapy and cancer treatment

We summarize the most important advances in RNA delivery and nanomedicine.We describe lipid nanoparticle-based RNA therapeutics and the impacts on the development of novel drugs.The fundamental properties of the key RNA members are described.We introduced recent advances in the nanoparticles to deliver RNA to defined targets,with a focus on lipid nanoparticles(LNPs).We review recent advances in biomedical therapy based on RNA drug delivery and state-of-the-art RNA application platforms,including the treatment of different types of cancer.This review presents an overview of current LNPs based RNA therapies in cancer treatment and provides deep insight into the development of future nanomedicines sophisticatedly combining the unparalleled functions of RNA therapeutics and nanotechnology.

Defect self-assembly of metal-organic framework triggers ferroptosis to overcome resistance

The emergence of multidrug treatment resistance presents a hurdle for the successful chemotherapy of tumours.Ferroptosis,resulting from the iron-dependent accumulation of lipid peroxides,has the potential to reverse multidrug resistance.However,simultaneous delivery of the iron sources,ferroptosis inducers,drugs,and enhanced circulation carriers within matrices remains a significant challenge.Herein,we designed and fabricated a defect self-assembly of metal-organic framework(MOF)-red blood cell(RBC)membrane-camouflaged multi-drug-delivery nanoplatform for combined ferroptosis-apoptosis treatment of multidrug-resistant cancer.Ferroptosis and chemotherapeutic drugs are embedded in the centre of the iron(III)-based MOF at defect sites by coordination with metal clusters during a one-pot solvothermal synthesis process.The RBC membrane could camouflage the nanoplatform for longer circulation.Our results demonstrate that this defect self-assembly-enabled MOF-membrane-camouflaged nanoplatform could deplete the glutathione,amplify the reactive oxidative species oxidative stress,and enable remarkable anticancer properties.Our work provides an alternative strategy for overcoming multidrug resistance,which could regulate the fluidity and permeability of the cell membrane by ferroptosis to downregulate of P-glycoprotein protein expression by ferroptosis.This defect self-assembly-enabled MOF-membrane-camouflaged multi-drug-delivery nanoplatform has great therapeutic potential.

Tea-derived carbon materials as anode for high-performance sodium ion batteries

Sodium-ion batteries(SIB) have attracted widespread attention in large-scale energy storage fields owing to the abundant reserve in the earth and similar properties of sodium to lithium. Biomass-based carbon materials with low-cost, controllable structure, simple processing technology, and environmental friendliness tick almost all the right boxes as one of the promising anode materials for SIB. Herein, we present a simple novel strategy involving tea tomenta biomass-derived carbon anode with enhanced interlayer carbon distance(0.44 nm) and high performance, which is constructed by N,P co-doped hard carbon(Tea-1100-NP) derived from tea tomenta. The prepared Tea-1100-NP composite could deliver a high reversible capacity(326.1 m Ah/g at 28 m A/g), high initial coulombic efficiency(ICE = 90% at 28 m A/g),stable cycle life(262.4 m Ah/g at 280 m A/g for 100 cycles), and superior rate performance(224.5 m Ah/g at 1400 m A/g). Experimental results show that the excellent electrochemical performance of Tea-1100-NP due to the high number of active N,P-containing groups, and disordered amorphous structures provide ample active sites and increase the conductivity, meanwhile, large amounts of microporous shorten the Na+diffusion distance as well as quicken ion transport. This work provides a new type of N,P co-doped high-performance tomenta-derived carbon, which may also greatly promote the commercial application of SIB.

Evaluation of DNA adduct damage using G-quadruplex-based DNAzyme

Toxicity assessment is a major problem in pharmaceutical candidates and industry chemicals development.However,due to the lack of practical analytical methods for DNA adduct analysis,the safety evaluation of drug and industry chemicals was severely limited.Here,we develop a DNAzyme-based method to detect DNA adduct damage for toxicity assessment of drugs and chemicals.Among 18 structural variants of G4 DNAzyme,EA2 DNAzyme exhibits an obvious DNA damaging effect of styrene oxide(SO)due to its unstable structure.The covalent binding of SO to DNAzyme disrupts the Hoogsteen hydrogen bonding sites of G-plane guanines and affects the formation of the G4 quadruplex.DNA damage chemicals reduce the peroxidase activity of the G4 DNAzyme to monitor the DNA adduct damage by disrupting the structural integrity of the G4 DNAzyme.Our method for genotoxic assessment of pharmaceutical candidates and industrial chemicals can elucidate the complex chemical pathways leading to toxicity,predict toxic effects of chemicals,and evaluate possible risks to human health.

Microfluidic chemostatic bioreactor for high-throughput screening and sustainable co-harvesting of biomass and biodiesel in microalgae

As a renewable and sustainable source for energy,environment,and biomedical applications,microalgae and microalgal biodiesel have attracted great attention.However,their applications are confined due to the cost-efficiency of microalgal mass production.One-step strategy and continuous culturing systems could be solutions.However,current studies for optimization throughout microalgae-based biofuel production pipelines are generally derived from the batch culture process.Better tools are needed to study algal growth kinetics in continuous systems.A microfluidic chemostatic bioreactor was presented here,providing low-bioadhesive cultivations for algae in a cooperative environment of gas,nutrition,and temperature(GNT)involved with high throughput.The chip was used to mimic the continuous culture environment of bioreactors.It allowed simultaneously studying of 8×8 different chemostatic conditions on algal growth and oil production in parallel on a 7×7 cm^(2)footprint.On-chip experiments of batch and continuous cultures of Chlorella.sp.were performed to study growth and lipid accumulation under different nitrogen concentrations.The results demonstrated that microalgal cultures can be regulated to grow and accumulate lipids concurrently,thus enhancing lipid productivity in one step.The developed on-chip culturing condition screening,which was more suitable for continuous bioreactor,was achieved at a half shorter time,64-times higher throughput,and less reagent consumption.It could be used to establish chemostat cultures in continuous bioreactors which can dramatically accelerate the development of renewable and sustainable algal for CO_(2)fixation and biosynthesis and related systems for advanced sustainable energy,food,pharmacy,and agriculture with enormous social and ecological benefits.