Biomaterials and tissue engineering in traumatic brain injury:novel perspectives on promoting neural regeneration

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.

Natural sources,refined extraction,biosynthesis,metabolism,and bioactivities of dietary polymethoxyflavones(PMFs)

Polymethoxyflavones(PMFs)are a type of uncommon dietary flavonoids,characterized by more than one methoxy group,which exist in limited plant species,like Citrus species and Kaempferia parviflora.In addition,different PMFs,such as nobiletin,sinensetin,tangeretin,and casticin,have been isolated from these natural sources.PMFs have received increasing attention due to their multiple bioactivities,such as antioxidant,anti-inflammatory,anti-cancer,metabolic regulatory,immunoregulatory,neuroprotective,and skin protective effects.These bioactivities of PMFs should be associated with the regulation of critical molecular targets and the interaction with gut microbiota.In order to provide a comprehensive and updated review of PMFs,their natural sources,refined extraction,biosynthesis,metabolism,and bioactivities are summarised and discussed,with the emphasis on the molecular mechanisms of PMFs on regulating different chronic diseases.Overall,PMFs may be promising flavonoids to the forefront of nutraceuticals for the prevention and/or treatment of certain human chronic diseases.

Effects of friction stir processing and nano-hydroxyapatite on the microstructure,hardness,degradation rate and in-vitro bioactivity of WE43 alloy for biomedical applications

Nowadays,magnesium alloys are emerging in biomedical implants for their similar properties to natural bones.However,the rapid degradation of magnesium alloys in biological media hinders successful implantation.Refinement of microstructure,as well as reinforcement particles can significantly improve the degradation rate.In this work,multi-pass friction stir processing(FSP)was proposed to synthesize WE43/nano-hydroxyapatite(n HA)surface composite,the microstructure,reinforced particle distribution,micro-hardness,corrosion behavior and in-vitro bioactivity were studied.The subsequent FSP passes of WE43 alloy and WE43/n HA composite refined the grain size which was reduced by 94.29%and 95.92%(2.63 and 1.88μm,respectively)compared to base metal after three passes.This resulted in increasing the microhardness by 120%(90.86 HV0.1)and 135%(105.59 HV0.1)for the WE43 and WE43-n HA,respectively.It is found that increasing FSP passes improved the uniform distribution of n HA particles within the composite matrix which led to improved corrosion resistance and less degradation rate.The corrosion rate of the FSPed WE43/n HA composite after three passes was reduced by 38.2%(4.13 mm/year)and the degradation rate was reduced by 69.7%(2.87 mm/y).This is attributed to secondary phase(Mg24Y5and Mg41Nd5)particle fragmentation and redistribution,as well as a homogeneous distribution of n HA.Additionally,the growing Ca-P and Mg(OH)2layer formed on the surface represented a protective layer that reduced the degradation rate.The wettability test revealed a relatively hydrophilic surface with water contact angle of 49.1±2.2°compared to 71.2±2.1°for base metal.Also,biomineralization test showed that apatite layer grew after immersion 7d in simulated body fluid with atomic ratio of Ca/P 1.60 approaching the stoichiometric ratio(1.67)indicating superior bioactivity of FSPed WE43/n HA composite after three passes.These results raise that the grain refinement by FSP and introduction of n HA particles significantly improved the degradation rate and in-vitro bioactivity of WE43 alloy for biomedical applications.

Valorization of Camellia oleifera oil processing byproducts to value-added chemicals and biobased materials: A critical review

The C.oleifera oil processing industry generates large amounts of solid wastes,including C.oleifera shell(COS)and C.oleifera cake(COC).Distinct from generally acknowledged lignocellulosic biomass(corn stover,bamboo,birch,etc.),Camellia wastes contain diverse bioactive substances in addition to the abundant lignocellulosic components,and thus,the biorefinery utilization of C.oleifera processing byproducts involves complicated processing technologies.This reviewfirst summarizes various technologies for extracting and converting the main components in C.oleifera oil processing byproducts into value-added chemicals and biobased materials,as well as their potential applications.Microwave,ultrasound,and Soxhlet extractions are compared for the extraction of functional bioactive components(tannin,flavonoid,saponin,etc.),while solvothermal conversion and pyrolysis are discussed for the conversion of lignocellulosic components into value-added chemicals.The application areas of these chemicals according to their properties are introduced in detail,including utilizing antioxidant and anti-in-flammatory properties of the bioactive substances for the specific application,as well as drop-in chemicals for the substitution of unrenewable fossil fuel-derived products.In addition to chemical production,biochar fabricated from COS and its applications in thefields of adsorption,supercapacitor,soil remediation and wood composites are comprehensively reviewed and discussed.Finally,based on the compositions and structural characteristics of C.oleifera byproducts,the development of full-component valorization strategies and the expansion of the appli-cationfields are proposed.

Aflatoxin B1： Toxicity, bioactivation and detoxification in the polyphagous caterpillar Trichoplusia ni

Trichoplusia ni caterpillars are polyphagous foliage-feeders and rarely likely to encounter aflatoxin B1 （AFB1）, a mycotoxin produced by Aspergillus flavus and A. parasiticus, in their host plants. To determine how T. ni copes with AFB 1, we evaluated the toxicity ofAFB 1 to T. ni caterpillars at different developmental stages and found that AFB 1 tolerance significantly increases with larval development. Diet incorporation of AFB 1 at 1μg/g completely inhibited larval growth and pupation of newly hatched larvae, but 3μg/g AFB 1 did not have apparent toxic effects on larval growth and pupation of caterpillars that first consume this compound 10 days after hatching. Piperonyl butoxide, a general inhibitor of cytochrome P450 monooxygenases （P450s）, reduced the toxicity of AFB 1, suggesting that AFB1 is bioactivated in T. ni and this bioactivation is mediated by P450s. Some plant allelochemicals, including flavonoids such as fiavones, furanocoumarins such as xanthotoxin and imperatorin, and furanochromones such as visnagin, that induce P450s in other lepidopteran larvae ameliorated AFBI toxicity, suggesting that P450s are also involved in AFB 1 detoxification in T. ni.

Betalains protect various body organs through antioxidant and anti-inflammatory pathways

Betalains are natural coloring pigments with betalamic acid as the core structure of all subclasses.Besides their coloring properties,betalains exhibit various biological activities,including antioxidant and anti-inflammatory properties,which are highly imperative.Further in-vivo studies reported that betalains protect various body organs,leading to health enhancement.Body organs,including the heart,liver,kidney,lung,etc.,are important for a healthy life.However,these organs can be affected or damaged by various stress factors,toxicants,and harmful substances.Recent studies have claimed that betalains could protect all vital organs of the body through antioxidant and anti-inflammatory mechanisms.This review article described the in-vivo antioxidant and anti-inflammatory activities of betalains in various cell-line or animal models.A comprehensive discussion has been provided on the mechanism of action of betalains in protecting various body organs,including cardio-protective effect,hepato-protective ability,renal protection capacity,repro-protective ability,neuro-protective effect,lung protection,and gut protection ability.Finally,future research directions and conclusions have been outlined.

Research advance of Bacillus velezensis:bioinformatics,characteristics,and applications

Bacillus velezensis is a Gram-positive and spore-forming bacterium.It has potent antimicrobial properties that can be used to promote plant growth and as a pesticide by inhibiting pathogens.B.velezensis has the capability to generate a diverse range of enzymes that have potential applications in various fields,such as enzyme production,fermented food,degradation of pollutants,and bioenergy.In addition,B.velezensis is a promising probiotic.It possesses high bile-salt tolerance characteristics and has a high success rate of colonization in the intestinal mucosa.Besides,the strain can also regulate gut microbiota constitute by increasing the number of beneficial microorganisms and decreasing the number of pathogens.Furthermore,based on its special properties,including high-yield protease production and high salt-tolerance,B.velezensis shows potential for use in marine protein fermentation,opening up new avenues for the development of novel food products and bioactive peptides.In addition,B.velezensis can shorten the fermentation time as well as improve the nutritional value and flavor of fermented food.The safety of B.velezensis for food production was evaluated.This review provides valuable insights into the potential uses and benefits of B.velezensis,particularly in the context of fermented foods.

Bioactivities,Mechanisms,Production,and Potential Application of Bile Acids in Preventing and Treating Infectious Diseases

Infectious diseases are a global public health problem,with emerging and re-emerging infectious diseases on the rise worldwide.Therefore,their prevention and treatment are still major challenges.Bile acids are common metabolites in both hosts and microorganisms that play a significant role in controlling the metabolism of lipids,glucose,and energy.Bile acids have historically been utilized as first-line,valuable therapeutic agents for related metabolic and hepatobiliary diseases.Notably,bile acids are the major active ingredients of cow bezoar and bear bile,which are commonly used traditional Chinese medicines(TCMs)with the therapeutic effects of clearing heat,detoxification,and relieving wind and spasm.In recent years,the promising performance of bile acids against infectious diseases has attracted attention from the scientific community.This paper reviews for the first time the biological activities,possible mechanisms,production routes,and potential applications of bile acids in the treatment and prevention of infectious diseases.Compared with previous reviews,we comprehensively summarize existing studies on the use of bile acids against infectious diseases caused by pathogenic microorganisms that are leading causes of global morbidity and mortality.In addition,to ensure a stable supply of bile acids at affordable prices,it is necessary to clarify the biosynthesis of bile acids in vivo,which will assist scientists in elucidating the accumulation of bile acids and discovering how to engineer various bile acids by means of chemosynthesis,biosynthesis,and chemoenzymatic synthesis.Finally,we explore the current challenges in the field and recommend a development strategy for bile-acid-based drugs and the sustainable production of bile acids.The presented studies suggest that bile acids are potential novel therapeutic agents for managing infectious diseases and can be artificially synthesized in a sustainable way.

Mechanisms and active substances of targeting lipid peroxidation in ferroptosis regulation

Ferroptosis is a novel form of cell death driven by iron-dependent lipid peroxidation and it is implicated in various diseases,such as liver disease,acute kidney injury,cardiovascular disease,neurodegenerative disease and cancer.Lipid-based reactive oxygen species(ROS),particularly lipid hydroperoxides in the cellular membrane can lead to membrane disruption and cell death mediated by ferroptosis.There are three necessary stages involving in the process of lipid peroxidation regulation in ferroptosis,including the synthesis of membrane phospholipids,initiation of lipid peroxidation and clearance of lipid peroxides.In this review,we summarized the molecular modulation mechanisms of lipid peroxidation in ferroptosis from the above three stages,as well as various ferroptosis modulators targeting lipid peroxidation,including commonly used products,natural bioactive compounds and selenocompounds.Collectively,these findings suggest the vital role of lipid peroxidation in ferroptosis,and targeting lipid peroxidation in ferroptosis is potential to treat ferroptosis-associated diseases.

Antibacterial HA-coatings on bioresorbable Mg alloy

In this study,a calcium-phosphate coating was formed on a Mg-Mn-Ce alloy by the plasma electrolytic oxidation(PEO).The antibiotic vancomycin,widely used in the treatment of infections caused by Staphylococcus aureus(S.aureus),was impregnated into the coating.Samples with vancomycin showed high bactericidal activity against S.aureus.The mechanical and electrochemical properties of the formed coatings were studied,as well as in vitro cytotoxicity tests and in vivo tests on mature male rats were performed.According to SEM,EDS,XRD and XPS data,coatings had a developed morphology and contained hydroxyapatite,which indicates high biocompatibility.The analysis of roughness of coatings without and with vancomycin did not reveal any differences,confirming the high roughness of the samples.During electrochemical tests,an increase in corrosion resistance by more than two times after the application of PEO coatings was revealed.According to the results of an in vivo study,after 28 days of the implantation of samples with calcium phosphate PEO coating and vancomycin,no signs of inflammation were observed,while an inflammatory reaction developed in the area of implantation of bare alloy,followed by encapsulation.Antibiotic release tests from the coatings show a sharp decrease in the concentration of the released antibiotic on day 7 and then a gradual decrease until day 28.Throughout the experiment,no significant deviations in the condition and behavior of the animals were observed;clinical tests did not reveal a systemic toxic reaction.

Review on the Fabrication of Surface Functional Structures for Enhancing Bioactivity of Titanium and Titanium Alloy Implants

Titanium and its alloys have been widely applied in many biomedical fields because of its excellent mechanical properties,corrosion resistance and good biocompatibility.However,problems such as rejection,shedding and infection will occur after titanium alloy implantation due to the low biological activity of titanium alloy surface.The structures with specific functions,which can enhance osseointegration and antibacterial properties,are fabricated on the surface of titanium implants to improve the biological activity between the titanium implants and human tissues.This paper presents a comprehensive review of recent developments and applications of surface functional structure in titanium and titanium alloy implants.The applications of surface functional structure on different titanium and titanium alloy implants are introduced,and their manufacturing technologies are summarized and compared.Furthermore,the fabrication of various surface functional structures used for titanium and titanium alloy implants is reviewed and analyzed in detail.Finally,the challenges affecting the development of surface functional structures applied in titanium and titanium alloy implants are outlined,and recommendations for future research are presented.

Bioactive compounds in Hericium erinaceus and their biological properties:a review

Hericium erinaceus is a nutritious edible and medicinal fungi,rich in a variety of functional active ingredients,with various physiological functions such as antioxidation,anticancer,and enhancing immunity.It is also effective in protecting the digestive system and preventing neurodegenerative diseases.In this review paper,we summarize the sources,structures and efficacies of the main active components in H.erinaceus fruiting body,mycelium,and culture media,and update the latest research progress on their biological activities and the related molecular mechanisms.Based on this information,we provide detailed challenges in current research,industrialization and information on the active ingredients of H.erinaceus.Perspectives for future studies and new applications of H.erinaceus are proposed.

Could natural phytochemicals be used to reduce nitrogen excretion and excreta‑derived N_(2)O emissions from ruminants?

Ruminants play a critical role in our food system by converting plant biomass that humans cannot or choose not to consume into edible high-quality food.However,ruminant excreta is a significant source of nitrous oxide(N_(2)O),a potent greenhouse gas with a long-term global warming potential 298 times that of carbon dioxide.Natural phytochemicals or forages containing phytochemicals have shown the potential to improve the efficiency of nitrogen(N)utilization and decrease N_(2)O emissions from the excreta of ruminants.Dietary inclusion of tannins can shift more of the excreted N to the feces,alter the urinary N composition and consequently reduce N_(2)O emissions from excreta.Essential oils or saponins could inhibit rumen ammonia production and decrease urinary N excretion.In grazed pastures,large amounts of glucosinolates or aucubin can be introduced into pasture soils when animals consume plants rich in these compounds and then excrete them or their metabolites in the urine or feces.If inhibitory compounds are excreted in the urine,they would be directly applied to the urine patch to reduce nitrification and subsequent N_(2)O emissions.The phytochemicals’role in sustainable ruminant production is undeniable,but much uncertainty remains.Inconsistency,transient effects,and adverse effects limit the effectiveness of these phytochemicals for reducing N losses.In this review,we will identify some current phytochemicals found in feed that have the potential to manipulate ruminant N excretion or mitigate N_(2)O production and deliberate the challenges and opportunities associated with using phytochemicals or forages rich in phytochemicals as dietary strategies for reducing N excretion and excreta-derived N_(2)O emissions.

Pharmacological effects of bioactive agents in earthworm extract:A comprehensive review

This review compiles information from the literature on the chemical composition,pharmacological effects,and molecular mechanisms of earthworm extract(EE)and suggests possibilities for clinical translation of EE.We also consider future trends and concerns in this domain.We summarize the bioactive components of EE,including G-90,lysenin,lumbrokinase,antimicrobial peptides,earthworm serine protease(ESP),and polyphenols,and detail the antitumor,antithrombotic,antiviral,antibacterial,anti-i nflammatory,analgesic,antioxidant,wound-healing,antifibrotic,and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies.We further propose the potential of EE for clinical translation in anticancer and lipid-modifying therapies,and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance.The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis.Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix.The glycolipoprotein extract G-90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage.Earthworms have evolved a well-developed defense mechanism to fight against microbial infections,and the bioactive agents in EE have shown good antibacterial,fungal,and viral properties in in vitro and in vivo experiments and can alleviate inflammatory responses caused by infections,effectively reducing pain.Recent studies have also highlighted the role of EE in lowering blood glucose.EE shows high medicinal value and is expected to be a source of many bioactive compounds.

Initial therapeutic evidence of a borosilicate bioactive glass(BSG)and Fe_(3)O_(4)magnetic nanoparticle scaffold on implant-associated Staphylococcal aureus bone infection

Implant-associated Staphylococcus aureus(S.aureus)osteomyelitis is a severe challenge in orthopedics.While antibiotic-loaded bone cement is a standardized therapeutic approach for S.aureus osteomyelitis,it falls short in eradicating Staphylococcus abscess communities(SACs)and bacteria within osteocyte-lacuna canalicular network(OLCN)and repairing bone defects.To address limitations,we developed a borosilicate bioactive glass(BSG)combined with ferroferric oxide(Fe_(3)O_(4))magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities.We conducted comprehensive assessments of the osteoinductive,immunomodulatory,antibacterial properties,and thermal response of this scaffold,with or without an alternating magnetic field(AMF).Utilizing a well-established implant-related S.aureus tibial infection rabbit model,we evaluated its antibacterial performance in vivo.RNA transcriptome sequencing demonstrated that BSG+5%Fe_(3)O_(4)enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs.Notably,BSG+5%Fe_(3)O_(4)upregulated gene expression of NOD-like receptor and TNF pathway in MSCs,alongside increased the expression of osteogenic factors(RUNX2,ALP and OCN)in vitro.Flow cytometry on macrophage exhibited a polarization effect towards M2,accompanied by upregulation of anti-inflammatory genes(TGF-β1 and IL-1Ra)and downregulation of pro-inflammatory genes(IL-6 and IL-1β)among macrophages.In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG+5%Fe_(3)O_(4)+AMF at 42 days.Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42,along with new bone formation,signifying effective control of S.aureus osteomyelitis.Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment.

Chemical incorporation of SiO_(2) into TiO_(2) layer by green plasma enhancer and quencher agents for synchronized improvements in the protective and bioactive properties

This study explores the dynamic interaction between environmentally sustainable plasma enhancer and quencher agents during the incorporation of SiO_(2) into a TiO_(2) layer,with the primary objective of simultaneously augmenting protective and bioactive attributes.This enhancement is realized through the synergistic utilization of Tetraethyl orthosilicate(TE)and Stevia(ST)within a plasma-assisted oxidation process.To achieve this goal,Ti–6Al–4V alloy underwent oxidation in an electrolyte solution containing acetate-glycerophosphate,with the addition of TE and ST separately and in combination.TE,as a silicon oxide(SiO_(2))precursor,facilitates the creation of a calcium-rich,rough,porous layer by undergoing hydrolysis to generate silanol groups(Si–OH),which subsequently condense into silicon-oxygen-silicon(Si–O–Si)bonds,resulting in SiO_(2) formation.In contrast,ST acts as a plasma quencher,absorbing highly reactive plasma species during the oxidation process,reducing energy levels,and diminishing sparking intensity.The combination of TE and ST results in moderate sparking,balancing Stevia's quenching effect and TE's sparking influence.As a result,this coating exhibits enhanced corrosion resistance and bioactivity compared to using either ST or TE alone.The study highlights the potential of this synergistic approach for advanced TiO_(2)-based coatings.

Nutritional values,bioactive compounds and health benefits of purslane(Portulaca oleracea L.):a comprehensive review

Portulaca oleracea L.,commonly known as purslane,is a worldwide weed species belonging to the family Portulacaceae and has been known as“Global Panacea”.As one of the most widely consumed green vegetables and medicinal plants around the world,it has recently been re-evaluated as a potential“new crop”due to the properties that differentiate it as one of the best vegetable sources of omega-3 fatty acid(α-linolenic acid),as well as a variety of nutrients and phytochemicals.Accordingly,emerging research has found that purslane exhibits health-promoting properties like anti-inflammatory,anti-hyperglycemic,antioxidant,neuroprotective,and immunomodulatory.These findings suggest that this species possesses a potential using as a dietary supplement beyond potherb and traditional medicine.This review systematically summarizes the up-to-date research carried out on purslane,including the nutritional compositions,bioactive compounds,and health benefits it exerts as well as limitations,challenges,and future directions of research.Finally,we hope that this review would provide purslane with a comprehensive reference and future scope as functional and health-promoting food for disease prevention and treatment.

Virtual screening and directional preparation of xanthine oxidase inhibitory peptides derived from hemp seed protein

The traditional nutritional and medical hemp(Cannabis sativa L.)seed protein were explored for the discovery and directional preparation of new xanthine oxidase inhibitory(XOI)peptides by structure-based virtual screening,compound synthesis,in vitro bioassay and proteolysis.Six subtypes of hemp seed edestin and albumin were in silico hydrolyzed by 29 proteases,and 192 encrypted bioactive peptides were screened out.Six peptides showed to be XOI peptides,of which four(about 67%)were released by elastase hydrolysis.The peptide DDNPRRFY displayed the highest XOI activity(IC50=(2.10±0.06)mg/mL),acting as a mixed inhibitor.The pancreatic elastase directionally prepared XOI hemp seed protein hydrolysates,from which 6 high-abundance XOI peptides encrypted 3 virtually-screened ones including the DDNPRRFY.The novel outstanding hemp seed protein-derived XOI peptides and their virtual screening and directed preparation methods provide a promising and applicable approach to conveniently and efficiently explore food-derived bioactive peptides.

Nano-vibration exciter:Hypoxia-inducible factor 1 signaling pathway-mediated extracellular vesicles as bioactive glass substitutes for bone regeneration

Bioactive glasses(BG)play a vital role in angiogenesis and osteogenesis through releasing functional ions.However,the rapid ion release in the early stage will cause excessive accumulation of metal ions,which in turn leads to obvious cytotoxicity,long-term inflammation,and bone repair failure.Inspired by the vibration exciter,small extracellular vesicles(sEVs)obtained by treating mesenchymal stem cells with copper-doped bioactive glass(CuBG-sEVs),is prepared as a nano-vibration exciter.The nano-vibration exciter can convert the ion signals of CuBG into biochemical factor signals through hypoxia-inducible factor 1(HIF-1)signaling pathway and its activated autophagy,so as to better exert the osteogenic activity of BG.The results showed that CuBG extracts could significantly improve the enrichment of key miRNAs and increase the yield of CuBG-sEVs by activating HIF-1 signaling pathway and its activated autophagy.Cell experiments showed that CuBG-sEVs are favor to cell recruitment,vascularization and osteogenesis as the enrichment of key miRNAs.The animal experiments results showed that CuBG-sEVs stimulated angiogenesis mediated by CD31 and promoted bone regeneration by activating signaling pathways related to osteogenesis.These findings underscored the significant potential of sEVs as alternative strategies to better roles of BG.

Targeted screening of an anti-inflammatory polypeptide from Rhopilema esculentum Kishinouye cnidoblasts and elucidation of its mechanism in alleviating ulcerative colitis based on an analysis of the gut microbiota and metabolites

Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest.This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV(Pro-Lys-Lys-Val-Val)of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome.Specifically,the polypeptide composition of R.esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF/TOF-MS).Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α(TNF-α)than the original ligand.Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC;affect serum metabolites through the arachidonic acid,glycerophospholipid and linoleic acid metabolism pathways;and further alleviate UC symptoms.This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.