Tumor immunotherapy has been recognized by Science as the most promising therapeutic approach for tumor eradication,with engineered bacteria emerging as a particularly promising modality.As a novel drug delivery platf...Tumor immunotherapy has been recognized by Science as the most promising therapeutic approach for tumor eradication,with engineered bacteria emerging as a particularly promising modality.As a novel drug delivery platform,the engineered bacterial therapeutics demonstrate exceptional targeting precision and favorable safety profiles.Through attenuation and programmable control strategies,these systems enable highly specific drug delivery,showing significant therapeutic potential in oncology and inflammatory bowel disease(IBD).展开更多
Radiative cooling systems(RCSs)possess the distinctive capability to dissipate heat energy via solar and thermal radiation,making them suitable for thermal regulation and energy conservation applications,essential for...Radiative cooling systems(RCSs)possess the distinctive capability to dissipate heat energy via solar and thermal radiation,making them suitable for thermal regulation and energy conservation applications,essential for mitigating the energy crisis.A comprehensive review connecting the advancements in engineered radiative cooling systems(ERCSs),encompassing material and structural design as well as thermal and energy-related applications,is currently absent.Herein,this review begins with a concise summary of the essential concepts of ERCSs,followed by an introduction to engineered materials and structures,containing nature-inspired designs,chromatic materials,meta-structural configurations,and multilayered constructions.It subsequently encapsulates the primary applications,including thermal-regulating textiles and energy-saving devices.Next,it highlights the challenges of ERCSs,including maximized thermoregulatory effects,environmental adaptability,scalability and sustainability,and interdisciplinary integration.It seeks to offer direction for forthcoming fundamental research and industrial advancement of radiative cooling systems in real-world applications.展开更多
By leveraging the unique qualities of microorganisms,engineered living materials(ELMs)offer functional and economic advantages in everyday applications along with notable ecological benefits.This study contributes to ...By leveraging the unique qualities of microorganisms,engineered living materials(ELMs)offer functional and economic advantages in everyday applications along with notable ecological benefits.This study contributes to the growing field of biodesign by examining the potential of Flavobacteria for thermochromic ELMs.Many Flavobacteria,commonly found in marine environments,produce iridescent structural colorations as their colonies expand on semi-solid surfaces through gliding motility.In this study,we analyzed the effects of temperature variations on flavobacterium Cellulophaga lytica PLY A 2,characterizing distinct changes in colony growth and iridescent colorations at a macroscopic and microscopic scale.Using scanning electron microscopy,we investigated the relationship between iridescent color and the underlying cell-based optical structures.By providing insights into the temperature-responsive behavior of Flavobacteria,our findings highlight their potential for future thermochromic ELMs-with applications ranging from sustainable food packaging to smart textiles-while encouraging further characterization studies within biodesign research.展开更多
Although manganese Prussian blue analogues(Mn-PBAs)offer advantages as cost-effective,high-energy-density cathode materials for sodium-ion batteries,their practical application is severely constrained by substantial c...Although manganese Prussian blue analogues(Mn-PBAs)offer advantages as cost-effective,high-energy-density cathode materials for sodium-ion batteries,their practical application is severely constrained by substantial capacity degradation during long-term cycling.This performance deterioration is closely associated with the structural instability of the material during the cycling process,which is mainly attributed to the gradual dissolution of the active material into the electrolyte and severe lattice distortion during Na+intercalation/deintercalation.Fortunately,the aforementioned challenges can be effectively addressed by fabricating an in situ engineered nickel cage(ISE-NC)on Mn-PBAs(denoted as Mn-PBAs-NC).Experimental characterization combined with theoretical calculations reveals that this spontaneously formed nickel cage not only suppresses the diffusion of Mn-PBAs into the electrolyte but also acts as a structural stabilizer,significantly alleviating lattice distortion during cycling.This dual stabilization mechanism ensures remarkable cycling stability,with Mn-PBAs-NC delivering a retained capacity of 96.4 mA h g^(−1)(80%capacity retention)over 2,300 cycles at 2 C,elevating the cycle life of Mn-PBAs to unprecedented levels.展开更多
Parkinson’s disease is characterized by synucleinopathy-associated neurodegeneration.Previous studies have shown that glucagon-like peptide-1(GLP-1)has beneficial effects in a mouse model of Parkinson’s disease indu...Parkinson’s disease is characterized by synucleinopathy-associated neurodegeneration.Previous studies have shown that glucagon-like peptide-1(GLP-1)has beneficial effects in a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.However,the effect of GLP-1 on intrinsic synuclein malfunction remains unclear.In this study,we investigated the effect of Lactococcus lactis MG1363-pMG36e-GLP-1 on parkinsonism in SncaA53T transgenic mice and explored the underlying mechanisms.Our data showed that Lactococcus lactis MG1363-pMG36e-GLP-1 inhibited dopaminergic neuronal death,reduced pathological aggregation ofα-synuclein,and decreased movement disorders in SncaA53T transgenic mice.Furthermore,Lactococcus lactis MG1363-pMG36e-GLP-1 downregulated lipopolysaccharide-related inflammation,reduced cerebral activation of microglia and astrocytes,and promoted cell survival via the GLP-1 receptor/PI3K/Akt pathway in the substantia nigra.Additionally,Lactococcus lactis MG1363-pMG36e-GLP-1 decreased serum levels of pro-inflammatory molecules including lipopolysaccharide,lipopolysaccharide binding protein,interleukin-1β,and interleukin-6.Gut histopathology and western blotting further revealed that Lactococcus lactis MG1363-pMG36e-GLP-1 increased the expression of gut integrity-related proteins and reduced lipopolysaccharide-related inflammation by reversing gut dysbiosis in SncaA53T transgenic mice.Our findings showed that the beneficial effect of Lactococcus lactis MG1363-pMG36e-GLP-1 on parkinsonism traits in SncaA53T transgenic mice is mediated by microglial polarization and the reversal of dysbiosis.Collectively,our findings suggest that Lactococcus lactis MG1363-pMG36e-GLP-1 is a promising therapeutic agent for the treatment of Parkinson’s disease.展开更多
Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the del...Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the delivery efficiency,we engineered three artesunate(ART) derivatives,AC_(15)-L(linear),AC_(15)-B(branched),and AC_(15)-C(cyclic) with distinct aliphatic chain architectures.Unexpectedly,we observed that AC_(15)-C exhibited superior cytotoxicity against 4T1 breast cancer cells,and had the highest binding affinity for Lon protease 1(LONP1)(-72.6 kcal/mol).Subsequently,disulfide bond-containing lipid-PEG(DSPESS-PEG2K) modified chain architecture-engineered ART derivatives nanoassemblies(NAs) were developed to mitigate solubility-related limitations while enhancing targeting precision.Molecular docking and experimental validation demonstrated that ART derivatives inhibited LONP1 through hydrophobic interactions while preserved Fe^(2+)-mediated Fenton-like reaction activity.In vitro and in vivo evaluations demonstrated that AC_(15)-C NAs outperformed free ART and other NAs,suppressing 4T1 tumor growth via dual action:LONP1-directed mitochondrial proteostasis collapse and reactive oxygen species(ROS) amplification through Fe^(2+)-ART interactions.This study elucidated a novel anti-tumor mechanism of ART through the rational design of derivatives with spatially configured aliphatic chains,and developed reductionresponsive NAs to provide an advanced delivery strategy.展开更多
Ionic phototheranostic agents have found extensive application in preclinical and clinical practice owing to their excellent biocompatibility and synergistic diagnostic-therapeutic integration.However,they still suffe...Ionic phototheranostic agents have found extensive application in preclinical and clinical practice owing to their excellent biocompatibility and synergistic diagnostic-therapeutic integration.However,they still suffer from certain limitations,such as short absorption/emission wavelengths,poor photostability,aggregation-caused fluorescence self-quenching,and diminished phototherapeutic efficacy upon aggregation,which collectively hinder their efficacy in complex clinical scenarios.To address these challenges,a second near-infrared(NIR-II)ionic phototheranostic agent,namely DT-BT-BIn,is rationally designed and synthesized via an innovative dual-acceptor engineering strategy.DT-BT-BIn ingeniously integrates benzothiadiazole and benzo[c,d]indolium as dual-acceptor units,which successfully achieves superior aggregation-induced NIR-II emission characteristics,highly efficient Type Ⅰ/Ⅱ photodynamic activity coupled with photothermal effect,and excellent photostability.Moreover,the self-assembled DT-BT-BIn nanoprobes(NPs)can be effectively internalized by cancer cells in vitro.Under irradiation,DT-BT-BIn NPs are capable of disrupting mitochondrial membrane potential,thereby inducing apoptotic cell death.Furthermore,in vivo investigations demonstrate DT-BT-BIn NPs can effectively accumulate at tumor location,enabling NIR-II fluorescence/photothermal imaging-guided precise tumor ablation,while simultaneously maintaining favorable biosafety toward normal tissues.Collectively,this study underscores the considerable promise of the dual-acceptor strategy in constructing high-performance NIR-II ionic phototheranostic agents and provides a new avenue for clinical precision cancer phototherapy.展开更多
Traumatic brain injury causes permanent cell death and can lead to long-term cognitive dysfunction,with no available treatments to repair the damaged brain tissue.Methods to track and understand traumatic brain injury...Traumatic brain injury causes permanent cell death and can lead to long-term cognitive dysfunction,with no available treatments to repair the damaged brain tissue.Methods to track and understand traumatic brain injury in humans are severely limited by the inaccessibility of living brain tissue,creating a need for in vitro model systems to study cellular mechanisms of degeneration and regeneration following injury.Here we describe methods to establish a 3D human brain tissue model,consisting of a silk-collagen composite scaffold seeded with human neurons,astrocytes,and microglia,to study neuro-regeneration after traumatic brain injury.Step-by-step fabrication,injury,and analytical assessments of the 3D“triculture”system are described.Using this tissue model system,we demonstrate that glial cells promote regeneration of neuronal networks within the injury site over several weeks post-injury.Further,we found that regenerating networks in the 3D triculture tissues did not secrete early markers of neurodegenerative disease,but displayed signs of excitatory/inhibitory imbalance,suggesting that pro-regenerative treatments for traumatic brain injury in the future may need to direct cell differentiation to promote proper function.The mechanical stability of this model system enables physiologically relevant impact injury and long-term culture capability,while its modular design enables modification of cell contents,extracellular matrix composition,and scaffold properties.This adaptability could allow the integration of patient-derived cells and genetic modifications to bridge research and clinical applications focused on personalized targeted therapies.This in vitro system provides a valuable platform for accelerating therapeutic advancements in traumatic brain injury and neurodegenerative disorders,ultimately improving patient outcomes.展开更多
Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–b...Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–brain barrier,extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions,including ischemic stroke,traumatic brain injury,neurodegenerative diseases,glioma,and psychosis.However,the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the body.To address these limitations,multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles,thereby enabling the delivery of therapeutic contents to specific tissues or cells.Therefore,this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles,exploring their applications in treating traumatic brain injury,ischemic stroke,Parkinson's disease,Alzheimer's disease,amyotrophic lateral sclerosis,glioma,and psychosis.Additionally,we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological diseases.This review offers new insights for developing highly targeted therapies in this field.展开更多
A new manufactured soil product (Turba) was produced using acidified bauxite residue into which 10% green waste compost had been incorporated. A laboratory/greenhouse experiment was carried out to determine if sand co...A new manufactured soil product (Turba) was produced using acidified bauxite residue into which 10% green waste compost had been incorporated. A laboratory/greenhouse experiment was carried out to determine if sand could be used as an ingredient or an amendment for Turba. Sand was added at rates of 0%, 5%, 10%, 25, 50% and 75% (w/w) in two different ways 1) by incorporating it into the Turba during its manufacture (IN) or 2) by mixing it with Turba aggregates after their manufacture (OUT). Incorporation of sand into Turba aggregates (IN) decreased the percentage of sample present as large aggregates (2 - 4 mm dia.) after crushing and sieving (<4 mm) and also reduced the stability of 2 - 4 mm dia. formed aggregates (to dry/wet sieving) and are therefore not recommended. In a 16-week greenhouse study, ryegrass shoot yields were greater in Turba than in sand [and decreased with increasing sand additions (OUT)] while root dry matter showed the opposite trend. The greater grass growth in Turba than sand was attributed to incipit water stress in plants grown in sand and this may have promoted greater allocation of assimilates to roots resulting in a greater root-to-top mass ratio. The much lower macroporosity in Turba coupled with the solid cemented nature of Turba aggregates resulted in production of thinner roots and therefore greater root length than in sand. Turba (manufactured from bauxite residue and compost added at 10% w/w) is a suitable medium for plant growth and there is no advantage in incorporating sand into, or with, the Turba aggregates.展开更多
Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules.Prepared through direct derivatization of natural extracts,they can include constituents enriched with elements and...Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules.Prepared through direct derivatization of natural extracts,they can include constituents enriched with elements and sub-structures that are less common in natural products compared to drugs.Fourteen such extracts were prepared through sequential reactions with hydrazine and a fluorinating reagent,and their α-glucosidase inhibition properties were compared.For the most bioactive mixture,a chemically modified propolis extract,enzyme inhibition increased 22 times due to the reaction sequence.Bio-guided fractionation led to the isolation of a new fluorinated pyrazole produced within the extract by chemical transformation of the flavonoid chrysin.The inhibitor results from the action of the two reagents used on four common functional groups present in natural products(carbonyl,phenol,aromatic carbon,and a double bond).The reactions led to the opening of a 6-member oxygenated heterocycle to produce a 5-member nitrogenated one,as well as the dehydroxylation and fluorination in two different positions of one of the aromatic rings of the natural starting material,all within a complex mixture of natural products.Overall,these transformations led to an approximately 20-fold increase in the α-glucosidase inhibition by the isolated inhibitor compared to its natural precursor.展开更多
In 1891,a New York surgeon named William Coley injected cancer patients with live bacteria,observing with fascination as some tumors shrank amid raging fevers.His crude experiments-later deemed reckless-nonetheless re...In 1891,a New York surgeon named William Coley injected cancer patients with live bacteria,observing with fascination as some tumors shrank amid raging fevers.His crude experiments-later deemed reckless-nonetheless revealed a tantalizing truth:The immune system,when properly provoked,could attack cancer.Over a century later,researchers have transformed this observation into a precision strike force.展开更多
Up to now,numerous emerging methods of cancer treatment including chemodynamic therapy,photothermal therapy,photodynamic therapy,sonodynamic therapy,immunotherapy and chemotherapy have rapidly entered a new stage of d...Up to now,numerous emerging methods of cancer treatment including chemodynamic therapy,photothermal therapy,photodynamic therapy,sonodynamic therapy,immunotherapy and chemotherapy have rapidly entered a new stage of development.However,the single treatment mode is often constrained by the complex tumor microenvironment.Recently,the nanomaterials and nanomedicine have emerged as promising avenues to overcome the limitation in cancer theranostics.Especially,metal-organic frameworks(MOFs)have gained considerable interests in cancer therapy because of their customizable morphologies,easy functionalization,large specific surface area,and good biocompatibility.Among these MOFs,iron-based MOFs(Fe-MOFs)are particularly promising for cancer treatment due to their properties as nano-photosensitizers,peroxidase-like activity,bioimaging contrast capabilities,and biodegradability.Utilizing their structural regularity and synthetic tunability,Fe-MOFs can be engineered to incorporate organic molecules or other inorganic nanoparticles,thereby creating multifunctional nanoplatforms for single or combined theranostic modes.Herein,the minireview focuses on the recent advancements of the Fe-MOFs-based nanoplatforms for self-enhanced imaging and treatment at tumor sites.Furthermore,the clinical research development of Fe-MOFs-based nanoplatforms is discussed,addressing key challenges and innovations for the future.Our review aims to provide novice researchers with a foundational understanding of advanced cancer theranostic modes and promote their clinical applications through the modification of Fe-MOFs.展开更多
As industrial pollution continues to contaminate ecosystems worldwide,researchers have engineered a breakthrough solution:a single bacterial strain that can tackle five persistent organic pollutants at once.
Engineered water systems such as wastewater treatment plants(WWTPs)are potential reservoirs of various biological risk factors(BRFs),including pathogens,antibiotic resistance genes(ARGs),and virulence factors(VFs).Cur...Engineered water systems such as wastewater treatment plants(WWTPs)are potential reservoirs of various biological risk factors(BRFs),including pathogens,antibiotic resistance genes(ARGs),and virulence factors(VFs).Currently,a BRF database relevant to engineered water systems on a global geographic scale is lacking.Here,we present the Global Wastewater Pathogen Database(GWPD),an online database that provides information on the diversity,abundance,and distribution of BRFs from 1302 metagenome samples obtained from 186 cities,68 countries,and six continents.We sorted these samples into six types:sewer networks,influent,anoxic activated sludge,oxic activated sludge,effluent,and receiving/natural waters.In total,476 pathogens,442 ARGs,and 246 VFs were identified.As a multifunctional database,GWPD provides an interactive visualization of these BRFs in a world map,an information retrieval interface,and an online one-click service for BRF annotation from metagenome sequencing data.GWPD is built on a web service framework,which can be readily extended to future versions of GWPD by adding more functional modules and connecting to other data sources,such as epidemic databases,to support risk assessment and control in the context of“One Health.”展开更多
Immunotherapy offers the promise of a potential cure for cancer,yet achieving the desired therapeutic effect can be challenging due to the immunosuppressive tumor microenvironments(TMEs) present in some tumors.Therefo...Immunotherapy offers the promise of a potential cure for cancer,yet achieving the desired therapeutic effect can be challenging due to the immunosuppressive tumor microenvironments(TMEs) present in some tumors.Therefore,robust immune system activation is crucial to enhance the efficacy of cancer immunotherapy in clinical applications.Bacteria have shown the ability to target the hypoxic TMEs while activating both innate and adaptive immune responses.Engineered bacteria,modified through chemical or biological methods,can be endowed with specific physiological properties,such as diverse surface antigens,metabolites,and improved biocompatibility.These unique characteristics give engineered bacteria distinct advantages in stimulating anti-cancer immune responses.This review explores the potential regulatory mechanisms of engineered bacteria in modulating both innate and adaptive immunity while also forecasting the future development and challenges of using engineered bacteria in clinical cancer immunotherapy.展开更多
Precancerous lesions of gastric cancer(PLGC)are crucial for the progression to gastric cancer,and early intervention in PLGC is pivotal in preventing its development into gastric cancer.In order to illustrate the mole...Precancerous lesions of gastric cancer(PLGC)are crucial for the progression to gastric cancer,and early intervention in PLGC is pivotal in preventing its development into gastric cancer.In order to illustrate the molecular mechanisms underlying PLGC and the roles of associated genes within these lesions,genetically engineered mouse models(GEMMs)have been developed.We systematically summarize the current GEMMs,and highlight the principal pathological mechanisms involved,including gastrin/gastric acid balance,inflammatory factors,the interplay between cancer-promoting and cancer-suppressing genes,and apoptotic pathways.We further discuss the mechanisms involved in the existing GEMMs of PLGC.展开更多
Practical applications of desulfurization gypsum are limited owing to its brittleness and low strength.To overcome these challenges,researchers have developed engineered desulfurization gypsum composites(EDGCs)by inco...Practical applications of desulfurization gypsum are limited owing to its brittleness and low strength.To overcome these challenges,researchers have developed engineered desulfurization gypsum composites(EDGCs)by incorporating ultrahigh molecular weight polyethylene(UHMWPE)fiber and sulfoaluminate cement(SAC).The mix ratio was optimized using response surface methodology(RSM).Experimental testing of EDGC under compressive and tensile loads led to the creation of a regression model that investigates the influence of variables and their interactions on the material’s compressive and tensile strengths.Additionally,microscopic morphology and hydration product composition were analyzed to explore the influence mechanism.The results indicated that EDGC’s compressive strength increased by up to 38.4%owing to a decreased water-binder ratio and higher SAC content.Similarly,tensile strength increased by up to 38.6%owing to increased SAC and fiber content.Moreover,EDGC demonstrated excellent strain-hardening behavior and multiple cracking characteristics,achieving a maximum tensile strain of nearly 3%.The research findings provide valuable insights for optimizing the performance of desulfurization gypsum.展开更多
Myocardial infarction(MI)is a challenging condition that results in scar formation on the ventricular wall,causing myocardial damage and ventricular thinning.Engineered cardiac patches(ECPs)designed to regenerate myoc...Myocardial infarction(MI)is a challenging condition that results in scar formation on the ventricular wall,causing myocardial damage and ventricular thinning.Engineered cardiac patches(ECPs)designed to regenerate myocardial tissue have been proposed to repair the ventricular wall and replenish myocardial cells.However,their clinical use is limited by manufacturing and fixation challenges.This study introduces a manufacturing strategy for a composite ECP,which comprises an antiadhesion shell layer,a conductive myocardial tissue,and an exosome-laden microneedle substrate.The ECP can anchor to the infarcted myocardium through its microneedle substrate.Meanwhile,its outer shell prevents nonspecific adhesion,enabling stable and suture-free attachment.Using this microneedle substrate,we applied a 3D-printed ECP in a rat model of post-MI repair.Our results showed that this strategy reduced left ventricular damage,improved cardiac ejection fraction,decreased the fibrotic area,increased ventricular wall thickness,improved microvascular recovery,and thus facilitated the repair of maladaptive ventricular remodeling post-MI.This microneedle substrate holds great promise for use in the fixation of patches during the repair of myocardial tissue and other organs,thereby promoting the clinical application of tissue-engineered patches.展开更多
Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent bioc...Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.展开更多
基金supported by the Hunan Natural Science Foundation(2023JJ20022).
文摘Tumor immunotherapy has been recognized by Science as the most promising therapeutic approach for tumor eradication,with engineered bacteria emerging as a particularly promising modality.As a novel drug delivery platform,the engineered bacterial therapeutics demonstrate exceptional targeting precision and favorable safety profiles.Through attenuation and programmable control strategies,these systems enable highly specific drug delivery,showing significant therapeutic potential in oncology and inflammatory bowel disease(IBD).
基金support from the Contract Research(“Development of Breathable Fabrics with Nano-Electrospun Membrane”,CityU ref.:9231419“Research and application of antibacterial and healing-promoting smart nanofiber dressing for children’s burn wounds”,CityU ref:PJ9240111)+1 种基金the National Natural Science Foundation of China(“Study of Multi-Responsive Shape Memory Polyurethane Nanocomposites Inspired by Natural Fibers”,Grant No.51673162)Startup Grant of CityU(“Laboratory of Wearable Materials for Healthcare”,Grant No.9380116).
文摘Radiative cooling systems(RCSs)possess the distinctive capability to dissipate heat energy via solar and thermal radiation,making them suitable for thermal regulation and energy conservation applications,essential for mitigating the energy crisis.A comprehensive review connecting the advancements in engineered radiative cooling systems(ERCSs),encompassing material and structural design as well as thermal and energy-related applications,is currently absent.Herein,this review begins with a concise summary of the essential concepts of ERCSs,followed by an introduction to engineered materials and structures,containing nature-inspired designs,chromatic materials,meta-structural configurations,and multilayered constructions.It subsequently encapsulates the primary applications,including thermal-regulating textiles and energy-saving devices.Next,it highlights the challenges of ERCSs,including maximized thermoregulatory effects,environmental adaptability,scalability and sustainability,and interdisciplinary integration.It seeks to offer direction for forthcoming fundamental research and industrial advancement of radiative cooling systems in real-world applications.
基金partial support from the Living Circular Labels project,funded by the Taskforce for Applied Research SIA’s KIEM programme(No.CIE.06.007)in the Netherlands。
文摘By leveraging the unique qualities of microorganisms,engineered living materials(ELMs)offer functional and economic advantages in everyday applications along with notable ecological benefits.This study contributes to the growing field of biodesign by examining the potential of Flavobacteria for thermochromic ELMs.Many Flavobacteria,commonly found in marine environments,produce iridescent structural colorations as their colonies expand on semi-solid surfaces through gliding motility.In this study,we analyzed the effects of temperature variations on flavobacterium Cellulophaga lytica PLY A 2,characterizing distinct changes in colony growth and iridescent colorations at a macroscopic and microscopic scale.Using scanning electron microscopy,we investigated the relationship between iridescent color and the underlying cell-based optical structures.By providing insights into the temperature-responsive behavior of Flavobacteria,our findings highlight their potential for future thermochromic ELMs-with applications ranging from sustainable food packaging to smart textiles-while encouraging further characterization studies within biodesign research.
基金financially supported by the Ten-thousand Talents Programthe K. C. Wong Pioneer Talent Program+3 种基金China Three Gorges Corporation (WWKY-2021–0027)Inner Mongolia Science and Technology Plan (2021ZD0033)the National Natural Science Foundation of China (52202121)funded by China Petroleum&Chemical Corporation (123091)
文摘Although manganese Prussian blue analogues(Mn-PBAs)offer advantages as cost-effective,high-energy-density cathode materials for sodium-ion batteries,their practical application is severely constrained by substantial capacity degradation during long-term cycling.This performance deterioration is closely associated with the structural instability of the material during the cycling process,which is mainly attributed to the gradual dissolution of the active material into the electrolyte and severe lattice distortion during Na+intercalation/deintercalation.Fortunately,the aforementioned challenges can be effectively addressed by fabricating an in situ engineered nickel cage(ISE-NC)on Mn-PBAs(denoted as Mn-PBAs-NC).Experimental characterization combined with theoretical calculations reveals that this spontaneously formed nickel cage not only suppresses the diffusion of Mn-PBAs into the electrolyte but also acts as a structural stabilizer,significantly alleviating lattice distortion during cycling.This dual stabilization mechanism ensures remarkable cycling stability,with Mn-PBAs-NC delivering a retained capacity of 96.4 mA h g^(−1)(80%capacity retention)over 2,300 cycles at 2 C,elevating the cycle life of Mn-PBAs to unprecedented levels.
基金supported by grants from the Jiangxi Provincial Natural Science Foundation,No.20242BAB26134(to XF)the National Natural Science Foundation of China,Nos.82060638(to TC),82060222(to XF),82460237(to XF)+1 种基金the Major Disciplines of Academic and Technical Leaders Project of Jiangxi Province,Nos.20194BCJ22032(to TC),20213BCJL22049(to XF)Science and Technology Plan of Jiangxi Health Planning Committee,No.202210390(to XF).
文摘Parkinson’s disease is characterized by synucleinopathy-associated neurodegeneration.Previous studies have shown that glucagon-like peptide-1(GLP-1)has beneficial effects in a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.However,the effect of GLP-1 on intrinsic synuclein malfunction remains unclear.In this study,we investigated the effect of Lactococcus lactis MG1363-pMG36e-GLP-1 on parkinsonism in SncaA53T transgenic mice and explored the underlying mechanisms.Our data showed that Lactococcus lactis MG1363-pMG36e-GLP-1 inhibited dopaminergic neuronal death,reduced pathological aggregation ofα-synuclein,and decreased movement disorders in SncaA53T transgenic mice.Furthermore,Lactococcus lactis MG1363-pMG36e-GLP-1 downregulated lipopolysaccharide-related inflammation,reduced cerebral activation of microglia and astrocytes,and promoted cell survival via the GLP-1 receptor/PI3K/Akt pathway in the substantia nigra.Additionally,Lactococcus lactis MG1363-pMG36e-GLP-1 decreased serum levels of pro-inflammatory molecules including lipopolysaccharide,lipopolysaccharide binding protein,interleukin-1β,and interleukin-6.Gut histopathology and western blotting further revealed that Lactococcus lactis MG1363-pMG36e-GLP-1 increased the expression of gut integrity-related proteins and reduced lipopolysaccharide-related inflammation by reversing gut dysbiosis in SncaA53T transgenic mice.Our findings showed that the beneficial effect of Lactococcus lactis MG1363-pMG36e-GLP-1 on parkinsonism traits in SncaA53T transgenic mice is mediated by microglial polarization and the reversal of dysbiosis.Collectively,our findings suggest that Lactococcus lactis MG1363-pMG36e-GLP-1 is a promising therapeutic agent for the treatment of Parkinson’s disease.
基金financially supported by the Liaoning Revitalization Talents Program (No.XLYC2403107)the Excellent Youth Science Foundation of Liaoning Province (No.2024JH3/10200046)the Basic Scientific Research Project of Liaoning Provincial Department of Education (No.LJ212410163015)。
文摘Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the delivery efficiency,we engineered three artesunate(ART) derivatives,AC_(15)-L(linear),AC_(15)-B(branched),and AC_(15)-C(cyclic) with distinct aliphatic chain architectures.Unexpectedly,we observed that AC_(15)-C exhibited superior cytotoxicity against 4T1 breast cancer cells,and had the highest binding affinity for Lon protease 1(LONP1)(-72.6 kcal/mol).Subsequently,disulfide bond-containing lipid-PEG(DSPESS-PEG2K) modified chain architecture-engineered ART derivatives nanoassemblies(NAs) were developed to mitigate solubility-related limitations while enhancing targeting precision.Molecular docking and experimental validation demonstrated that ART derivatives inhibited LONP1 through hydrophobic interactions while preserved Fe^(2+)-mediated Fenton-like reaction activity.In vitro and in vivo evaluations demonstrated that AC_(15)-C NAs outperformed free ART and other NAs,suppressing 4T1 tumor growth via dual action:LONP1-directed mitochondrial proteostasis collapse and reactive oxygen species(ROS) amplification through Fe^(2+)-ART interactions.This study elucidated a novel anti-tumor mechanism of ART through the rational design of derivatives with spatially configured aliphatic chains,and developed reductionresponsive NAs to provide an advanced delivery strategy.
基金supported by the National Natural Science Foundation of China(82572410,22405063,32300048,22307080)Guangdong Basic and Applied Basic Research Foundation(2023A1515110122,2024A1515010677,2024A1515012842,2024A1515012577)+3 种基金Characteristic Innovation Project of Guangdong Province General University(2024KTSCX166,2024KTSCX168)State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia Fund(SKL-HIDCA-2024-GJ3)Clinical and Basic Science&Technology Innovation Special Project of Guangdong Medical University(GDMULCJC2024161,GDMULCJC2024120)Guangdong Medical University Undergraduate Innovation and Entrepreneurship Education Base Project(JDXM2024042).
文摘Ionic phototheranostic agents have found extensive application in preclinical and clinical practice owing to their excellent biocompatibility and synergistic diagnostic-therapeutic integration.However,they still suffer from certain limitations,such as short absorption/emission wavelengths,poor photostability,aggregation-caused fluorescence self-quenching,and diminished phototherapeutic efficacy upon aggregation,which collectively hinder their efficacy in complex clinical scenarios.To address these challenges,a second near-infrared(NIR-II)ionic phototheranostic agent,namely DT-BT-BIn,is rationally designed and synthesized via an innovative dual-acceptor engineering strategy.DT-BT-BIn ingeniously integrates benzothiadiazole and benzo[c,d]indolium as dual-acceptor units,which successfully achieves superior aggregation-induced NIR-II emission characteristics,highly efficient Type Ⅰ/Ⅱ photodynamic activity coupled with photothermal effect,and excellent photostability.Moreover,the self-assembled DT-BT-BIn nanoprobes(NPs)can be effectively internalized by cancer cells in vitro.Under irradiation,DT-BT-BIn NPs are capable of disrupting mitochondrial membrane potential,thereby inducing apoptotic cell death.Furthermore,in vivo investigations demonstrate DT-BT-BIn NPs can effectively accumulate at tumor location,enabling NIR-II fluorescence/photothermal imaging-guided precise tumor ablation,while simultaneously maintaining favorable biosafety toward normal tissues.Collectively,this study underscores the considerable promise of the dual-acceptor strategy in constructing high-performance NIR-II ionic phototheranostic agents and provides a new avenue for clinical precision cancer phototherapy.
基金supported by funding from the U.S.Department of Defense,Nos.W911NF-23-1-0276,W81XWH2211065the NIH,No.P41EB027062(all to DLK).
文摘Traumatic brain injury causes permanent cell death and can lead to long-term cognitive dysfunction,with no available treatments to repair the damaged brain tissue.Methods to track and understand traumatic brain injury in humans are severely limited by the inaccessibility of living brain tissue,creating a need for in vitro model systems to study cellular mechanisms of degeneration and regeneration following injury.Here we describe methods to establish a 3D human brain tissue model,consisting of a silk-collagen composite scaffold seeded with human neurons,astrocytes,and microglia,to study neuro-regeneration after traumatic brain injury.Step-by-step fabrication,injury,and analytical assessments of the 3D“triculture”system are described.Using this tissue model system,we demonstrate that glial cells promote regeneration of neuronal networks within the injury site over several weeks post-injury.Further,we found that regenerating networks in the 3D triculture tissues did not secrete early markers of neurodegenerative disease,but displayed signs of excitatory/inhibitory imbalance,suggesting that pro-regenerative treatments for traumatic brain injury in the future may need to direct cell differentiation to promote proper function.The mechanical stability of this model system enables physiologically relevant impact injury and long-term culture capability,while its modular design enables modification of cell contents,extracellular matrix composition,and scaffold properties.This adaptability could allow the integration of patient-derived cells and genetic modifications to bridge research and clinical applications focused on personalized targeted therapies.This in vitro system provides a valuable platform for accelerating therapeutic advancements in traumatic brain injury and neurodegenerative disorders,ultimately improving patient outcomes.
基金supported by the National Natural Science Foundation of China,Nos.82171363,82371381(to PL),82171458(to XJ)Key Research and Development Project of Shaa nxi Province,Nos.2024SF-YBXM-404(to KY)。
文摘Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–brain barrier,extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions,including ischemic stroke,traumatic brain injury,neurodegenerative diseases,glioma,and psychosis.However,the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the body.To address these limitations,multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles,thereby enabling the delivery of therapeutic contents to specific tissues or cells.Therefore,this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles,exploring their applications in treating traumatic brain injury,ischemic stroke,Parkinson's disease,Alzheimer's disease,amyotrophic lateral sclerosis,glioma,and psychosis.Additionally,we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological diseases.This review offers new insights for developing highly targeted therapies in this field.
文摘A new manufactured soil product (Turba) was produced using acidified bauxite residue into which 10% green waste compost had been incorporated. A laboratory/greenhouse experiment was carried out to determine if sand could be used as an ingredient or an amendment for Turba. Sand was added at rates of 0%, 5%, 10%, 25, 50% and 75% (w/w) in two different ways 1) by incorporating it into the Turba during its manufacture (IN) or 2) by mixing it with Turba aggregates after their manufacture (OUT). Incorporation of sand into Turba aggregates (IN) decreased the percentage of sample present as large aggregates (2 - 4 mm dia.) after crushing and sieving (<4 mm) and also reduced the stability of 2 - 4 mm dia. formed aggregates (to dry/wet sieving) and are therefore not recommended. In a 16-week greenhouse study, ryegrass shoot yields were greater in Turba than in sand [and decreased with increasing sand additions (OUT)] while root dry matter showed the opposite trend. The greater grass growth in Turba than sand was attributed to incipit water stress in plants grown in sand and this may have promoted greater allocation of assimilates to roots resulting in a greater root-to-top mass ratio. The much lower macroporosity in Turba coupled with the solid cemented nature of Turba aggregates resulted in production of thinner roots and therefore greater root length than in sand. Turba (manufactured from bauxite residue and compost added at 10% w/w) is a suitable medium for plant growth and there is no advantage in incorporating sand into, or with, the Turba aggregates.
基金support by Universidad Nacional de Rosario(80020180300114UR and 80020180100128UR)CONICET(PIP No 11220200102423)FONCYT(PICT2019-02232 and PICT2021-1034)for the development of this work.
文摘Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules.Prepared through direct derivatization of natural extracts,they can include constituents enriched with elements and sub-structures that are less common in natural products compared to drugs.Fourteen such extracts were prepared through sequential reactions with hydrazine and a fluorinating reagent,and their α-glucosidase inhibition properties were compared.For the most bioactive mixture,a chemically modified propolis extract,enzyme inhibition increased 22 times due to the reaction sequence.Bio-guided fractionation led to the isolation of a new fluorinated pyrazole produced within the extract by chemical transformation of the flavonoid chrysin.The inhibitor results from the action of the two reagents used on four common functional groups present in natural products(carbonyl,phenol,aromatic carbon,and a double bond).The reactions led to the opening of a 6-member oxygenated heterocycle to produce a 5-member nitrogenated one,as well as the dehydroxylation and fluorination in two different positions of one of the aromatic rings of the natural starting material,all within a complex mixture of natural products.Overall,these transformations led to an approximately 20-fold increase in the α-glucosidase inhibition by the isolated inhibitor compared to its natural precursor.
文摘In 1891,a New York surgeon named William Coley injected cancer patients with live bacteria,observing with fascination as some tumors shrank amid raging fevers.His crude experiments-later deemed reckless-nonetheless revealed a tantalizing truth:The immune system,when properly provoked,could attack cancer.Over a century later,researchers have transformed this observation into a precision strike force.
基金National Key Research and Development Program of China(No.2022YFD2200602)111 Project(No.B20088)+1 种基金National Natural Science Foundation of China(Nos.52202345 and 31930076)the Heilongjiang Touyan Innovation Team Program(Tree Genetics and Breeding Innovation Team)。
文摘Up to now,numerous emerging methods of cancer treatment including chemodynamic therapy,photothermal therapy,photodynamic therapy,sonodynamic therapy,immunotherapy and chemotherapy have rapidly entered a new stage of development.However,the single treatment mode is often constrained by the complex tumor microenvironment.Recently,the nanomaterials and nanomedicine have emerged as promising avenues to overcome the limitation in cancer theranostics.Especially,metal-organic frameworks(MOFs)have gained considerable interests in cancer therapy because of their customizable morphologies,easy functionalization,large specific surface area,and good biocompatibility.Among these MOFs,iron-based MOFs(Fe-MOFs)are particularly promising for cancer treatment due to their properties as nano-photosensitizers,peroxidase-like activity,bioimaging contrast capabilities,and biodegradability.Utilizing their structural regularity and synthetic tunability,Fe-MOFs can be engineered to incorporate organic molecules or other inorganic nanoparticles,thereby creating multifunctional nanoplatforms for single or combined theranostic modes.Herein,the minireview focuses on the recent advancements of the Fe-MOFs-based nanoplatforms for self-enhanced imaging and treatment at tumor sites.Furthermore,the clinical research development of Fe-MOFs-based nanoplatforms is discussed,addressing key challenges and innovations for the future.Our review aims to provide novice researchers with a foundational understanding of advanced cancer theranostic modes and promote their clinical applications through the modification of Fe-MOFs.
文摘As industrial pollution continues to contaminate ecosystems worldwide,researchers have engineered a breakthrough solution:a single bacterial strain that can tackle five persistent organic pollutants at once.
基金supported by the National Natural Science Foundation of China(52321005,52293441,52293443,52230004)the Shenzhen Stability Support Key Program in Colleges and Universities of China(GXWD20231127195344001)+3 种基金the Natural Science Foundation of Guangdong Basic and Applied Basic Research Foundation(2024A1515010085)the Shenzhen Overseas High-level Talents Research Startup Program(20200518750C)the Shenzhen Science and Technology Program(KQTD20190929172630447)the Open Project of the Key Laboratory of Environmental Biotechnology,CAS(KF2021006).
文摘Engineered water systems such as wastewater treatment plants(WWTPs)are potential reservoirs of various biological risk factors(BRFs),including pathogens,antibiotic resistance genes(ARGs),and virulence factors(VFs).Currently,a BRF database relevant to engineered water systems on a global geographic scale is lacking.Here,we present the Global Wastewater Pathogen Database(GWPD),an online database that provides information on the diversity,abundance,and distribution of BRFs from 1302 metagenome samples obtained from 186 cities,68 countries,and six continents.We sorted these samples into six types:sewer networks,influent,anoxic activated sludge,oxic activated sludge,effluent,and receiving/natural waters.In total,476 pathogens,442 ARGs,and 246 VFs were identified.As a multifunctional database,GWPD provides an interactive visualization of these BRFs in a world map,an information retrieval interface,and an online one-click service for BRF annotation from metagenome sequencing data.GWPD is built on a web service framework,which can be readily extended to future versions of GWPD by adding more functional modules and connecting to other data sources,such as epidemic databases,to support risk assessment and control in the context of“One Health.”
基金supported by the Science and Technology Research Project of Jilin Education Bureau(No.JJKH20230804KJ)。
文摘Immunotherapy offers the promise of a potential cure for cancer,yet achieving the desired therapeutic effect can be challenging due to the immunosuppressive tumor microenvironments(TMEs) present in some tumors.Therefore,robust immune system activation is crucial to enhance the efficacy of cancer immunotherapy in clinical applications.Bacteria have shown the ability to target the hypoxic TMEs while activating both innate and adaptive immune responses.Engineered bacteria,modified through chemical or biological methods,can be endowed with specific physiological properties,such as diverse surface antigens,metabolites,and improved biocompatibility.These unique characteristics give engineered bacteria distinct advantages in stimulating anti-cancer immune responses.This review explores the potential regulatory mechanisms of engineered bacteria in modulating both innate and adaptive immunity while also forecasting the future development and challenges of using engineered bacteria in clinical cancer immunotherapy.
基金Supported by the National Administration of Traditional Chinese Medicine National Superior Specialty Project of Traditional Chinese Medicine,No.[2024]90Shanghai Municipal Administrator of Traditional Chinese Medicine Policy Letter[2024],No.20+1 种基金Science and Technology Development Fund of Shanghai University of Traditional Chinese Medicine,No.23KFL102Shuguang Hospital Siming Foundation Research Special Project,No.SGKJ-202304。
文摘Precancerous lesions of gastric cancer(PLGC)are crucial for the progression to gastric cancer,and early intervention in PLGC is pivotal in preventing its development into gastric cancer.In order to illustrate the molecular mechanisms underlying PLGC and the roles of associated genes within these lesions,genetically engineered mouse models(GEMMs)have been developed.We systematically summarize the current GEMMs,and highlight the principal pathological mechanisms involved,including gastrin/gastric acid balance,inflammatory factors,the interplay between cancer-promoting and cancer-suppressing genes,and apoptotic pathways.We further discuss the mechanisms involved in the existing GEMMs of PLGC.
基金The National Natural Science Foundation of China(No.51978504).
文摘Practical applications of desulfurization gypsum are limited owing to its brittleness and low strength.To overcome these challenges,researchers have developed engineered desulfurization gypsum composites(EDGCs)by incorporating ultrahigh molecular weight polyethylene(UHMWPE)fiber and sulfoaluminate cement(SAC).The mix ratio was optimized using response surface methodology(RSM).Experimental testing of EDGC under compressive and tensile loads led to the creation of a regression model that investigates the influence of variables and their interactions on the material’s compressive and tensile strengths.Additionally,microscopic morphology and hydration product composition were analyzed to explore the influence mechanism.The results indicated that EDGC’s compressive strength increased by up to 38.4%owing to a decreased water-binder ratio and higher SAC content.Similarly,tensile strength increased by up to 38.6%owing to increased SAC and fiber content.Moreover,EDGC demonstrated excellent strain-hardening behavior and multiple cracking characteristics,achieving a maximum tensile strain of nearly 3%.The research findings provide valuable insights for optimizing the performance of desulfurization gypsum.
基金supported by the Beijing Natural Science Foundation(Nos.7252285 and L246001)the National Natural Science Foundation of China(Nos.U21A20394 and 52305314)the National Key Research and Development Program of China(No.2023YFB4605800).
文摘Myocardial infarction(MI)is a challenging condition that results in scar formation on the ventricular wall,causing myocardial damage and ventricular thinning.Engineered cardiac patches(ECPs)designed to regenerate myocardial tissue have been proposed to repair the ventricular wall and replenish myocardial cells.However,their clinical use is limited by manufacturing and fixation challenges.This study introduces a manufacturing strategy for a composite ECP,which comprises an antiadhesion shell layer,a conductive myocardial tissue,and an exosome-laden microneedle substrate.The ECP can anchor to the infarcted myocardium through its microneedle substrate.Meanwhile,its outer shell prevents nonspecific adhesion,enabling stable and suture-free attachment.Using this microneedle substrate,we applied a 3D-printed ECP in a rat model of post-MI repair.Our results showed that this strategy reduced left ventricular damage,improved cardiac ejection fraction,decreased the fibrotic area,increased ventricular wall thickness,improved microvascular recovery,and thus facilitated the repair of maladaptive ventricular remodeling post-MI.This microneedle substrate holds great promise for use in the fixation of patches during the repair of myocardial tissue and other organs,thereby promoting the clinical application of tissue-engineered patches.
基金supported by the grants from University of Macao,China,Nos.MYRG2022-00221-ICMS(to YZ)and MYRG-CRG2022-00011-ICMS(to RW)the Natural Science Foundation of Guangdong Province,No.2023A1515010034(to YZ)。
文摘Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.