FUBP3 mediates the amyloid-β-induced neuronal NLRP3 expression

Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

Mesenchymal stem cell-derived extracellular vesicles in skin wound healing:roles,opportunities and challenges

Skin wounds are characterized by injury to the skin due to trauma,tearing,cuts,or contusions.As such injuries are common to all human groups,they may at times represent a serious socioeconomic burden.Currently,increasing numbers of studies have focused on the role of mesenchymal stem cell(MSC)-derived extracellular vesicles(EVs)in skin wound repair.As a cell-free therapy,MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy.Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures,including the regeneration of vessels,nerves,and hair follicles.In addition,MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization,wound angiogenesis,cell proliferation,and cell migration,and by inhibiting excessive extracellular matrix production.Additionally,these structures can serve as a scaffold for components used in wound repair,and they can be developed into bioengineered EVs to support trauma repair.Through the formulation of standardized culture,isolation,purification,and drug delivery strategies,exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair.In conclusion,MSCderived EV-based therapies have important application prospects in wound repair.Here we provide a comprehensive overview of their current status,application potential,and associated drawbacks.

Controllable Histotomy Based on Hierarchical Magnetic Microneedle Array Robots

Investigation of patient-derived primary tissues is of great importance in the biomedical field,but recent tissue slicing and cultivation techniques still have difficulties in satisfying clinical requirements.Here,we propose a controllable histotomy strategy that utilizes hierarchical magnetic microneedle array robots to tailor primary tissues and establish the desired high-throughput tissue-on-a-chip.This histotomy is performed using a three-dimensional printed,mortise-tenon-structured slicing device coupled with a magnetic-particle-loaded and pagoda-shaped microneedle array scaffold.Due to the multilayered struc-ture of these microneedles,tissue specimens can be fixed onto the microneedle scaffold via mechanical interlocking,thereby effectively avoiding tissue slipping during the slicing process.Owing to the encapsu-lation of magnetic microneedle fragments,these tissue pieces can act as magnetically responsive biohybrid microrobots and can be easily manipulated by magnetic fields,facilitating their separation,transportation,and dynamic culture.Using this strategy,we demonstrate that primary pancreatic cancer tissues can be tailored into tiny pieces and cultured in multilayered microfluidic chips for efficient high-throughput drug screening,indicating the promising future of this technique’s application in clinical settings.

Biomimetic Erythrocyte-Like Particles from Microfluidic Electrospray for Tissue Engineering

Microparticles have demonstrated value for regenerative medicine.Attempts in this field tend to focus on the development of intelligent multifunctional microparticles for tissue regeneration.Here,inspired by erythrocytes-associated self-repairing process in damaged tissue,we present novel biomimetic erythrocyte-like microparticles(ELMPs).These ELMPs,which are composed of extracellular matrix-like hybrid hydrogels and the functional additives of black phosphorus,hemoglobin,and growth factors(GFs),are generated by using a microfluidic electrospray.As the resultant ELMPs have the capacity for oxygen delivery and near-infrared-responsive release of both GFs and oxygen,they would have excellent biocompatibility and multifunctional performance when serving as microscaffolds for cell adhesion,stimulating angiogenesis,and adjusting the release profile of cargoes.Based on these features,we demonstrate that the ELMPs can stably overlap to fill a wound and realize controllable cargo release to achieve the desired curative effect of tissue regeneration.Thus,we consider our biomimetic ELMPs with discoid morphology and cargo-delivery capacity to be ideal for tissue engineering.

Spatial transcriptomics:recent developments and insights in respiratory research

The respiratory system's complex cellular heterogeneity presents unique challenges to researchers in this field.Although bulk RNA sequencing and single-cell RNA sequencing(scRNA-seq)have provided insights into cell types and heterogeneity in the respiratory system,the relevant specific spatial localization and cellular interactions have not been clearly elucidated.Spatial transcriptomics(ST)has filled this gap and has been widely used in respiratory studies.This review focuses on the latest iterative technology of ST in recent years,summarizing how ST can be applied to the physiological and pathological processes of the respiratory system,with emphasis on the lungs.Finally,the current challenges and potential development directions are proposed,including high-throughput full-length transcriptome,integration of multi-omics,temporal and spatial omics,bioinformatics analysis,etc.These viewpoints are expected to advance the study of systematic mechanisms,including respiratory studies.

Recent advances in essential oils and their nanoformulations for poultry feed

Antibiotics in poultry feed to boost growth performance are becoming increasingly contentious due to concerns over antimicrobial resistance development.Essential oils(EOs),as natural,plant-derived compounds,have demonstrated antimicrobial and antioxidant properties.EOs may potentially improve poultry health and growth performance when included in poultry feed.Nevertheless,the incorporation of EOs as nutritional additives is hindered by their high volatility,low water solubility,poor intestinal absorption,and sensitivity to environmental conditions.Recently,nanoencapsulation strategies using nanoformulations have emerged as a potential solution to these challenges,improving the stability and bioavailability of EOs,and enabling targeted delivery in poultry feed.This review provides an overview of the antioxidant and antibacterial properties of EOs,the current limitations of their applications in poultry feed,and the recent advancements in nano-engineering to overcome these limitations.Furthermore,we outline the potential future research direction on EO nanoformulations,emphasizing their promising role in advancing sustainable poultry nutrition.

SIL1 improves cognitive impairment in APP23/PS45 mice by regulating amyloid precursor protein processing and Aβ generation

SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study,the role of SIL1 in APP processing was explored both in vitro and in vivo.In the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695.In the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates.Western blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant parameters.Results indicated that SIL1 expression decreased in APP23/PS45 mice.Overexpression of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in vitro.Conversely,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 cells.Furthermore,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice.Importantly,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice.These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.

The marriage of immunomodulatory,angiogenic,and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scafold for military medicine

Background:Most bone-related injuries to grassroots troops are caused by training or accidental injuries.To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops,it is imperative to develop new strategies and scafolds to promote bone regeneration.Methods:In this study,a porous piezoelectric hydrogel bone scafold was fabricated by incorporating polydopamine(PDA)-modified ceramic hydroxyapatite(PDA-hydroxyapatite,PHA)and PDA-modified barium titanate(PDABaTiO_(3),PBT)nanoparticles into a chitosan/gelatin(Cs/Gel)matrix.The physical and chemical properties of the Cs/Gel/PHA scafold with 0–10 wt%PBT were analyzed.Cell and animal experiments were performed to characterize the immunomodulatory,angiogenic,and osteogenic capabilities of the piezoelectric hydrogel scafold in vitro and in vivo.Results:The incorporation of BaTiO_(3) into the scafold improved its mechanical properties and increased self-generated electricity.Due to their endogenous piezoelectric stimulation and bioactive constituents,the prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory,angiogenic,and osteogenic capabilities;they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration,tube formation,and angiogenic differentiation of human umbilical vein endothelial cells(HUVECs)and facilitated the migration,osteodifferentiation,and extracellular matrix(ECM)mineralization of MC3T3-E1 cells.The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model.The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis,and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization.Conclusion:The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation,angiogenesis,and osteogenesis functions may be used as a substitute in periosteum injuries,thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat efectiveness in grassroots troops.

Self‑Healing Dynamic Hydrogel Microparticles with Structural Color for Wound Management

Chronic diabetic wounds confront a significant medical challenge because of increasing prevalence and difficult-healing circumstances.It is vital to develop multifunctional hydrogel dressings,with well-designed morphology and structure to enhance flexibility and effectiveness in wound management.To achieve these,we propose a self-healing hydrogel dressing based on structural color microspheres for wound management.The microsphere comprised a photothermal-responsive inverse opal framework,which was constructed by hyaluronic acid methacryloyl,silk fibroin methacryloyl and black phosphorus quantum dots(BPQDs),and was further re-filled with a dynamic hydrogel.The dynamic hydrogel filler was formed by Knoevenagel condensation reaction between cyanoacetate and benzaldehyde-functionalized dextran(DEX-CA and DEX-BA).Notably,the composite microspheres can be applied arbitrarily,and they can adhere together upon near-infrared irradiation by leveraging the BPQDs-mediated photothermal effect and the thermoreversible stiffness change of dynamic hydrogel.Additionally,eumenitin and vascular endothelial growth factor were co-loaded in the microspheres and their release behavior can be regulated by the same mechanism.Moreover,effective monitoring of the drug release process can be achieved through visual color variations.The microsphere system has demonstrated desired capabilities of controllable drug release and efficient wound management.These characteristics suggest broad prospects for the proposed composite microspheres in clinical applications.

Desipramine reverses remote memory deficits by activating calmodulin- CaMKII pathway in a UTX knockout mouse model of Kabuki syndrome

Background Kabukisyndrome(KS)is arare developmental disorder characterised by multiple congenital anomalies and intellectual disability.UTX(ubiquitously transcribed tetratricopeptide repeat,X chromosome),which encodes a histone demethylase,is one of the two major pathogenic risk genes for KS.Although intellectual disability is a key phenotype of KS,the role of UTX in cognitive function remains unclear.Currently,no targeted therapies are available for KS.Aims This study aimed to investigate how UTX regulates cognition,to explore the mechanisms underlying UTX dysfunction and to identify potential molecular targets for treatment.Methods WegeneratedUTXconditional knockoutmice and found that UTX deletion downregulated calmodulin transcription by disrupting H3K27me3(trimethylated histone H3 at lysine 27)demethylation.Results UTX-knockout mice showeddecreased phosphorylation of calcium/calmodulin-dependent protein kinase I,impaired long-term potentiation and deficit in remote contextual fear memory.These effects were reversed by an Food and Drug Administration-approved drug desipramine.Conclusions Our results reveal an epigenetic mechanism underlying the important role of UTX in synaptic plasticity and cognitive function,and suggest that desipramine could be a potential treatment for KS.

Deep near infrared light-excited stable synergistic photodynamic and photothermal therapies based on P-IR890 nano-photosensitizer constructed via a non-cyanine dye

The cyanine dyes represented by IR780 can achieve synergistic photodynamic therapy(PDT)and photothermal therapy(PTT)under the stimulation of near-infrared(NIR)light(commonly 808 nm).Unfortunately,the stability of NIR-excited cyanine dyes is not satisfactory.These cyanine dyes can be attacked by self-generated reactive oxygen species(ROS)during PDT processes,resulting in structural damage and rapid degradation,which is fatal for phototherapy.To address this issue,a novel non-cyanine dye(IR890)was elaborately designed and synthesized by our team.The maximum absorption wavelength of IR890 was located in the deep NIR region(ca.890 nm),which was beneficial for further improving tissue penetration depth.Importantly,IR890 exhibited good stability when continuously illuminated by deep NIR light.To improve the hydrophilicity and biocompatibility,the hydrophobic IR890 dye was grafted onto the side chain of hydrophilic polymer(POEGMA-b-PGMA-g-C≡CH)via click chemistry.Then,the synthesized POEGMA-b-PGMA-g-IR890 amphiphilic polymerwas utilized to prepare P-IR890 nano-photosensitizer via self-assembly method.Under irradiation with deep NIR light(850 nm,0.5 W/cm^(2),10 min),the dye degradation rate of P-IR890 was less than 5%.However,IR780 was almost completely degraded with the same light output power density and irradiation duration.In addition,P-IR890 could stably generate a large number of ROS and heat at the same time.It was rarely reported that the stable synergistic combination therapy of PDT and PTT could be efficiently performed by a single photosensitizer via irradiation with deep NIR light.P-IR890 exhibited favorable anti-tumor outcomes through apoptosis pathway.Therefore,the P-IR890 could provide a new insight into the design of photosensitizers and new opportunities for synergistic combination therapy of PDT and PTT.

Biomass Microcapsules with Stem Cell Encapsulation for Bone Repair

Bone defects caused by trauma,tumor,or osteoarthritis remain challenging due to the lack of effective treatments in clinic.Stem cell transplantation has emerged as an alternative approach for bone repair and attracted widespread attention owing to its excellent biological activities and therapy effect.The attempts to develop this therapeutic approach focus on the generation of effective cell delivery vehicles,since the shortcomings of direct injection of stem cells into target tissues.Here,we developed a novel core-shell microcapsule with a stem cell-laden core and a biomass shell by using all-aqueous phase microfluidic electrospray technology.The designed core-shell microcapsules showed a high cell viability during the culture procedure.In addition,the animal experiments exhibited that stem cell-laden core-shell microcapsules have good biocompatibility and therapeutic effect for bone defects.This study indicated that the core-shell biomass microcapsules generated by microfluidic electrospray have promising potential in tissue engineering and regenerative medicine.

Equilibrium folding and unfolding dynamics to reveal detailed free energy landscape of src SH3 protein by magnetic tweezers

Src SH3 protein domain is a typical two-state protein which has been confirmed by research of denaturant-induced unfolding dynamics.Force spectroscopy experiments by optical tweezers and atomic force microscopy have measured the force-dependent unfolding rates with different kinds of pulling geometry.However,the equilibrium folding and unfolding dynamics at constant forces has not been reported.Here,using stable magnetic tweezers,we performed equilibrium folding and unfolding dynamic measurement and force-jump measurement of src SH3 domain with tethering points at its N-and C-termini.From the obtained force-dependent transition rates,a detailed two-state free energy landscape of src SH3 protein is constructed with quantitative information of folding free energy,transition state barrier height and position,which exemplifies the capability of magnetic tweezers to study protein folding and unfolding dynamics.

Stimuli-Responsive Gene Delivery Nanocarriers for Cancer Therapy

Gene therapy provides a promising approach in treating cancers with high efficacy and selectivity and few adverse effects.Currently,the development of functional vectors with safety and effectiveness is the intense focus for improving the delivery of nucleic acid drugs for gene therapy.For this purpose,stimuli-responsive nanocarriers displayed strong potential in improving the overall efficiencies of gene therapy and reducing adverse effects via effective protection,prolonged blood circulation,specific tumor accumulation,and controlled release profile of nucleic acid drugs.Besides,synergistic therapy could be achieved when combined with other therapeutic regimens.This review summarizes recent advances in various stimuliresponsive nanocarriers for gene delivery.Particularly,the nanocarriers responding to endogenous stimuli including pH,reactive oxygen species,glutathione,and enzyme,etc.,and exogenous stimuli including light,thermo,ultrasound,magnetic field,etc.,are introduced.Finally,the future challenges and prospects of stimuli-responsive gene delivery nanocarriers toward potential clinical translation are well discussed.The major objective of this review is to present the biomedical potential of stimuli-responsive gene delivery nanocarriers for cancer therapy and provide guidance for developing novel nanoplatforms that are clinically applicable.

Microfluidic Generation of Multicomponent Soft Biomaterials

Soft biomaterials hold great potential for a plethora of biomedical applications because of their deforma-bility,biodegradability,biocompatibility,high bioactivity,and low antigenicity.Multicomponent soft bio-materials are particularly attractive as a way of accommodating components made of different materials and generating combinative functions.Microfluidic technology has emerged as an outstanding tool in generating multicomponent materials with elaborate structures and constituents,in that it can manipu-late multiphasic flows precisely on the micron scale.In recent decades,much progress has been achieved in the microfluidic fabrication of multicomponent soft biomaterials with finely defined physicochemical properties capable of controllable therapeutics delivery,three-dimensional(3D)cell culture,flexible devices and wearable electronics,and biosensing for molecules.In the paper,we summarize current pro-gress in multicomponent soft biomaterials derived from microfluidics and emphasize their applications in biomedical fields.We also provide an outlook of the remaining challenges and future trends in this field.

Fluorination Increases Hydrophobicity at the Macroscopic Level but not at the Microscopic Level

Hydrophobic interactions have been studied before in detail based on hydrophobic polymers,such as polystyrene(PS).Because fluorinated materials have relatively low surface energy,they often show both oleophobicity and hydrophobicity at the macroscopic level.However,it remains unknown how fluorination of hydrophobic polymer influences hydrophobicity at the microscopic level.We synthesized PS and fluorine-substituted PS(FPS)by employing the reversible addition-fragmentation chain transfer polymerization method.Contact angle measurements confirmed that FPS is more hydrophobic than PS at the macroscopic level due to the introduction of fluorine.However,single molecule force spectroscopy experiments showed that the forces required to unfold the PS and FPS nanoparticles in water are indistinguishable,indicating that the strength of the hydrophobic effect that drives the self-assembly of PS and FPS nanoparticles is the same at the microscopic level.The divergence of hydrophobic effect at the macroscopic and microscopic level may hint different underlying mechanisms:the hydrophobicity is dominated by the solvent hydration at the microscopic level and the surface-associated interaction at the macroscopic level.

Hierarchically Inverse Opal Porous Scaffolds from Droplet Microfluidics for Biomimetic 3D Cell Co-Culture

With the advantages of better mimicking the specificity of natural tissues,three-dimensional(3D)cell culture plays a major role in drug development,toxicity testing,and tissue engineering.However,existing scaffolds or microcarriers for 3D cell culture are often limited in size and show suboptimal performance in simulating the vascular complexes of living organisms.Therefore,we present a novel hierarchically inverse opal porous scaffold made via a simple microfluidic approach for promoting 3D cell co-culture techniques.The designed scaffold is constructed using a combined concept involving an emulsion droplet template and inert polymer polymerization.This work demonstrates that the resultant scaffolds ensure a sufficient supply of nutrients during cell culture,so as to achieve large-volume cell culture.In addition,by serially planting different cells in the scaffold,a 3D co-culture system of endothelial-cellencapsulated hepatocytes can be developed for constructing certain functional tissues.It is also demonstrated that the use of the proposed scaffold for a co-culture system helps hepatocytes to maintain specific in vivo functions.These hierarchically inverse opal scaffolds lay the foundation for 3D cell culture and even the construction of biomimetic tissues.

HuR-mediated nucleocytoplasmic translocation of HOTAIR relieves its inhibition of osteogenic differentiation and promotes bone formation

Bone marrow mesenchymal stem cell(BMSC)osteogenic differentiation and osteoblast function play critical roles in bone formation,which is a highly regulated process.Long noncoding RNAs(lncRNAs)perform diverse functions in a variety of biological processes,including BMSC osteogenic differentiation.Although several studies have reported that HOX transcript antisense RNA(HOTAIR)is involved in BMSC osteogenic differentiation,its effect on bone formation in vivo remains unclear.Here,by constructing transgenic mice with BMSC(Prx1-HOTAIR)-and osteoblast(Bglap-HOTAIR)-specific overexpression of HOTAIR,we found that Prx1-HOTAIR and Bglap-HOTAIR transgenic mice show different bone phenotypes in vivo.Specifically,Prx1-HOTAIR mice showed delayed bone formation,while Bglap-HOTAIR mice showed increased bone formation.HOTAIR inhibits BMSC osteogenic differentiation but promotes osteoblast function in vitro.Furthermore,we identified that HOTAIR is mainly located in the nucleus of BMSCs and in the cytoplasm of osteoblasts.HOTAIR displays a nucleocytoplasmic translocation pattern during BMSC osteogenic differentiation.We first identified that the RNA-binding protein human antigen R(HuR)is responsible for HOTAIR nucleocytoplasmic translocation.HOTAIR is essential for osteoblast function,and cytoplasmic HOTAIR binds to miR-214 and acts as a ceRNA to increase Atf4 protein levels and osteoblast function.BglapHOTAIR mice,but not Prx1-HOTAIR mice,showed alleviation of bone loss induced by unloading.This study reveals the importance of temporal and spatial regulation of HOTAIR in BMSC osteogenic differentiation and bone formation,which provides new insights into precise regulation as a target for bone loss.

基于脱细胞后鱼皮细胞外基质的生物打印水凝胶纺织品用于创面修复

创面修复具有普遍性、治疗困难、患者众多和医疗负担沉重的特点,一直是临床研究的热点。为了满足特定需求,研究者投入了大量科研力量,致力于开发各种个性化需求和功能的伤口敷料。在这方面,我们提出了一种基于鱼皮脱细胞的细胞外基质(d ECM)水凝胶纺织品用于创面修复。鱼源的d ECM具有理想的生物相容性,并且通过生物打印技术制备的纺织品在细胞黏附和增殖方面表现出卓越的性能。此外,基于d ECM的水凝胶纺织品采用生物打印技术生成,因此具有可调节的多孔结构,使整个纺织品具备良好的透气性。而且,水凝胶骨架上的多孔结构高比表面积使其能够负载多种活性分子,从而提高创面愈合效果。通过体内研究结果,我们证明了这种制备的纺织品负载活性药物分子姜黄素(Cur)和碱性成纤维细胞生长因子(b FGF)能够显著加速慢性创面的修复过程。这些结果表明鱼皮d ECM纺织品在创面修复和生物医学工程领域具有潜在的价值。

Enhanced photonic nanojets for submicron patterning

Photonic nanojets(PNJs) have a wide range of applications in laser processing, nanolithography, optical highdensity storage, super-resolution microscopy, and other fields due to their processing capacity to overcome the diffraction limit. Herein, we control static microsphere be developed into the motion state to fabricate vector graphics nano-grooves.The microspheres roll on the substrate while the laser is kept synchronously irradiated, and the overlapping PNJ ablated craters form patterned grooves on the indium-tin oxide(ITO) substrate. Thus, PNJ has been expanded from “point”processing to “line” processing. The fabricated nano grooves have high continuity and consistency. Whereas, the precise customization of critical groove dimension can be achieved via modulation in diameter and kinetics of dielectric microshperes. Furthermore, by etching vectographs on an ITO conductive glass substrate, we demonstrated the advantages and potential of the proposed method in nanopatterning. The proposed method effectively reduces the cost and complexity of photonic nanojets applied in nanopatterning. The proposed nanopatterning methodology will play a vital role in the fabrication of semiconductor materials, sensors, microfluidic devices, surface-enhanced Raman scattering(SERS), biomedicine, nanoscience and nanoengineering.