Nattokinase as a functional food ingredient:therapeutic applications and mechanisms in age-related diseases

Consumption of natto,a traditional eastern Asian food made of fermented soybeans by Bacillus subtilis,has long been linked to healthy aging and longer human lifespan.As the key thrombolytic ingredient of natto,the serine protease nattokinase(NK)has been developed into a widely-used dietary supplement.NK has shown excellent anti-thrombus,thrombolytic,and anti-inflammation activities that potentially delay aging and provide therapeutic effects on aging-related diseases.In this review,we critically overview the experimental and clinical evidence in the past 20 years that support the beneficial function of NK in the prevention and treatment of aging-related diseases,including cardiovascular diseases,Alzheimer’s disease,other abnormalities and cancer.We focus on the underlying molecular mechanisms and recent advances in application methods that are aimed at further development of NK for healthier aging of modern society.The challenges and unsolved issues in this area are also discussed.

Development of a Functional Food Snack Product Utilizing Underexplored and Underutilized Ingredients: Spirulina Microalgae and Bilberry

Spirulina, a protein-rich cyanobacterium, and Bilberry, a dark berry, have the potential to be used as functional food ingredients in the food industry. These two underexplored and underutilized ingredients were used to develop an adolescent-friendly functional snack food product in the light of food industry trends. Stages of product development, shelf life/physiochemical analysis (texture, pH, color, and water activity) and sensory evaluation were utilized in developing a functional snack mini muffin containing Spirulina and Bilberry. Aqueous (AQ) and 80% ethanol (ET) extracts of mini muffin formulations (chocolate, 1% Spirulina (S) + 4% Bilberry (B), 2% Spirulina (S) + 8% Bilberry (B)) were prepared using a standard protocol. Antioxidant potential was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric Reducing Antioxidant Potential (FRAP) assays. Utilizing a 5-point hedonic scale (1—Dislike very much, 2—Dislike a little, 3—Neither like nor dislike, 4—Like a little, 5—Like very much), 3 mini muffin formulations (chocolate, 1% S + 4% B, 2% S +8% B), were tested among consumer panelists, with 1% S + 4% B being the most acceptable based on taste, texture, color, aroma, appearance, etc. Texture (post-peak (N) of the mini muffin did not vary between chocolate and 1 S% + 4% B formulations;however, 2% S + 8% B was 1.09 times higher compared to its counterparts. pH, color, and water activity remained constant over the 9-day shelf-life period. The Spirulina and Bilberry muffins developed exhibited antioxidant activities (highest in 2% S + 8% B), and were accepted by the sensory panelists for color, taste, mouthfeel, and aroma (panelists preferred 1% S + 4% B).

Targeting gut microbiota in osteoporosis:impact of the microbial based functional food ingredients

Osteoporosis is the most common bone disorder,characterized by low bone mineral density and microarchitectural deterioration of the bone tissue,which increases the susceptibility to fracture.In the past decade,emerging research findings reported the implication of gut microbiota on bone health and osteoporosis pathology.Osteoporotic patients or individuals with a lower bone mineral density exhibit an alteration of the gut microbiota at several taxonomic levels.Additional reports demonstrate that gut microbiota regulates bone metabolism through the modulation of the gut function(mineral availability and absorption,gut integrity),the immune system,and the endocrine system.Thus,based on the vital role of gut microbiota on bone health,it has emerged as a novel therapeutic target for the prevention of bone loss and the treatment of osteoporosis.Microbial-based functional food ingredients,such as probiotics,prebiotics,synbiotics,and fermented foods,have been developed to alter the gut microbiota composition and function and thus,to provide benefits to the host bone health.Despite promising initial results,microbial-based therapies are still under investigation.Moreover,additional animal studies and clinical trials are needed to understand the interactions between gut microbiota and bone metabolism before further applications.

Transcriptomic analysis of Andrias davidianus meat and experimental validation for exploring its bioactive components as functional foods

Andrias davidianus(Chinese giant salamander,CGS)is the largest and oldest extant amphibian species in the world and is a source of prospective functional food in China.However,the progress of functional peptides mining was slow due to lack of reference genome and protein sequence data.In this study,we illustrated full-length transcriptome sequencing to interpret the proteome of CGS meat and obtain 10703 coding DNA sequences.By functional annotation and amino acid composition analysis,we have discovered various genes related to signal transduction,and 16 genes related to longevity.We have also found vast variety of functional peptides through protein coding sequence(CDS)analysis by comparing the data obtained with the functional peptide database.Val-Pro-Ile predicted by the CDS analysis was released from the CGS meat through enzymatic hydrolysis,suggesting that our approach is reliable.This study suggested that transcriptomic analysis can be used as a reference to guide polypeptide mining in CGS meat,thereby providing a powerful mining strategy for the bioresources with unknown genomic and proteomic sequences.

The hypoglycemic potential of phenolics from functional foods and their mechanisms

Long-term postprandial hyperglycemia is a primary risk factor for developing chronic metabolic diseases such as obesity,type 2 diabetes,and cardiovascular disease.Chronic hyperglycemia induces the glycation of proteins,oxidative stress,inflammation and increases plasma insulin and lipid concentrations.Insulin resistance is the primary cause of postprandial excursions of blood glucose and lipids.Hyperglycemia can be treated by lowering dietary carbohydrates intake,digestion,and absorption.Various functional foods improve glucose metabolism by increasing insulin sensitivity and inhibitingα-glucosidase in the small intestine.Natural phytochemicals,especially active phenolics are good antioxidants and show anti-inflammatory action and regulate blood glucose.This review aimed to report on hypoglycemic properties of active phenolics from functional foods and their proposed anti-diabetic mechanisms.Nevertheless,further clinical trials are required to confirm the bioavailability,safety,and efficacy of phenolics,especially the dosage and duration of treatment,to avoid adverse effects and give better dietary recommendations.

Functional Nonparametric Predictions in Food Industry Using Near-Infrared Spectroscopy Measurement

Functional statistics is a new technique for dealing with data thatcan be viewed as curves or images. Parallel to this approach, the Near-InfraredReflectance (NIR) spectroscopymethodology has been used in modern chemistryas a rapid, low-cost, and exact means of assessing an object’s chemicalproperties. In this research, we investigate the quality of corn and cookiedough by analyzing the spectroscopic technique using certain cutting-edgestatistical models. By analyzing spectral data and applying functional modelsto it, we could predict the chemical components of corn and cookie dough.Kernel Functional Classical Estimation (KFCE), Kernel Functional QuantileEstimation (KFQE), Kernel Functional Expectile Estimation (KFEE),Semi-Partial Linear Functional Classical Estimation (SPLFCE), Semi-PartialLinear Functional Quantile Estimation (SPLFQE), and Semi-Partial LinearFunctional Expectile Estimation (SPLFEE) are models used to accuratelyestimate the different quantities present in Corn and Cookie dough. Theselection of these functional models is based on their ability to constructa forecast region with a high level of confidence. We demonstrate that theconsidered models outperform traditional models such as the partial leastsquaresregression and the principal component regression in terms of predictionaccuracy. Furthermore, we show that the proposed models are morerobust than competing models such as SPLFQE and SPLFEE in the sensethat data heterogeneity has no effect on their efficiency.

Natural and modified food hydrocolloids as gluten replacement in baked foods:Functional benefits

Gluten,the protein responsible for the superior viscoelastic properties of refined wheat flour dough over glutenfree cereals,causes celiac disease in people susceptible to gluten-allergy.Moreover,the sustainability of using wheat flour in baked foods is threatened by its high cost,especially in countries that depend on imported wheat for their bakery industry.Research has shown that hydrocolloids serve as gluten replacements in baked foods,in response to these challenges.Food hydrocolloids are a class of high-molecular weight polysaccharides and proteins,which serve as functional ingredients in the food industry that modify the foods’rheological and textural properties.They function as stabilizers,viscosity modifiers,gelling agents,water binders,fibres,and inhibitors of ice crystal in foods.Further,food hydrocolloids have also been reported to possess health-promoting properties,such as lowering of postprandial blood glucose and plasma cholesterol concentrations,colon cancer prevention,and modulation of intestinal transit and satiety.They are obtained from plants,animals or microorganisms,and can be used in their natural or modified forms.The aim of this paper is to review the functional benefits of natural and modified hydrocolloids as gluten replacements in baked foods,emphasizing their physicochemical,nutraceutical,and sensorial importance.The application effects of food hydrocolloids as gluten substitutes in gluten-free baked products’quality were discussed.Also,some practical approaches to improve the quality of gluten-free baked products,in response to an increasing consumers’demand and the rising cost of refined wheat flour were highlighted.

The impact of demographic dynamics on food consumption and its environmental outcomes:Evidence from China

With increasing population and changing demographics,food consumption has experienced a significant transition in quantity and quality.However,a dearth of knowledge remains regarding its environmental impacts and how it responds to demographic dynamics,particularly in emerging economies like China.Using the two-stage Quadratic Almost Demand System(QUAIDS)model,this study empirically examines the impact of demographic dynamics on food consumption and its environmental outcomes based on the provincial data from 2000 to 2020 in China.Under various scenarios,according to changes in demographics,we extend our analysis to project the long-term trend of food consumption and its environmental impacts,including greenhouse gas(GHG)emissions,water footprint(WF),and land appropriation(LA).The results reveal that an increase in the proportion of senior people significantly decreases the consumption of grain and livestock meat and increases the consumption of poultry,egg,and aquatic products,particularly for urban residents.Moreover,an increase in the proportion of males in the population leads to higher consumption of poultry and aquatic products.Correspondingly,in the current scenario of an increased aging population and sex ratio,it is anticipated that GHG emissions,WF,and LA are likely to decrease by 1.37,2.52,and 3.56%,respectively.More importantly,in the scenario adhering to the standards of nutritional intake according to the Dietary Guidelines for Chinese Residents in 2022,GHG emissions,WF,and LA in urban areas would increase by 12.78,20.94,and 18.32%,respectively.Our findings suggest that changing demographics should be considered when designing policies to mitigate the diet-environment-health trilemma and achieve sustainable food consumption.

Profile of the Functional Categories of Food Additives in Industrial Foods Marketed in Senegal

Food additives, whether natural or artificial substances, are widely used around the world to improve the sensory quality of products, extend their shelf life and make them more competitive. However, the abusive and uncontrolled consumption of food additives is the cause of numerous illnesses and diseases such as poisoning, allergies, diabetes and numerous cancers. So, in addition to setting up control and regulatory bodies, it is becoming essential to keep a constant watch on the presence of food additives on the market. The aim of this study is to highlight the main categories of food additives in food products frequently sold on the Senegalese market. The methodology of the study is based on the identification of food additives from the information given on the labels of food packaging. Information was collected in markets in two (2) major regions of Senegal: Dakar and Saint-Louis. The results of our study show the presence of 153 food additives on the labels of 514 samples collected. Moreover, the frequency and diversity of additives depended on the food category. On the other hand, beyond their important technological and functional roles, some additives such as aspartame and monosodium glutamate have been implicated in pathologies, and others, such as titanium dioxide, are the subject of much controversy and even withdrawal in certain legislations for their impacts deemed potentially negative on consumer health.

Food-derived peptides with inhibitory capacity for HMG-CoA reductase activity: a potential nutraceutical for hypercholesterolemia

Cardiovascular diseases(CVDs)are the leading global cause of mortality and disease burden.Statins are the most prescribed lipid-lowering drugs to treat hypercholesterolemia and prevent CVDs.The biochemical mechanism of statins consists of competitive inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme(HMG-CoAR),the limiting enzyme in cholesterol biosynthesis.Due to statin intolerance in some patient groups,the search for new inhibitors is a field of great interest.This review focusses on the studies reporting the inhibitory effect of protein hydrolysates and biopeptides on the HMG-CoAR enzyme activity.The analysis of the action mechanism and physicochemical characteristics of the HMG-CoAR inhibitory peptides revealed that the molecular weight,amino acid composition,charge,and polarity are key aspects of the interaction with the HMG-CoAR enzyme.In conclusion,this review reveals the potential of using food peptides as new cholesterol-lowering agents and opens a new interesting field of research.However,clinical approaches are mandatory to confirm their therapeutic hypercholesterolemic effect.

Combining stochastic density functional theory with deep potential molecular dynamics to study warm dense matter

In traditional finite-temperature Kohn–Sham density functional theory(KSDFT),the partial occupation of a large number of high-energy KS eigenstates restricts the use of first-principles molecular dynamics methods at extremely high temperatures.However,stochastic density functional theory(SDFT)can overcome this limitation.Recently,SDFT and the related mixed stochastic–deterministic density functional theory,based on a plane-wave basis set,have been implemented in the first-principles electronic structure software ABACUS[Q.Liu and M.Chen,Phys.Rev.B 106,125132(2022)].In this study,we combine SDFT with the Born–Oppenheimer molecular dynamics method to investigate systems with temperatures ranging from a few tens of eV to 1000 eV.Importantly,we train machine-learning-based interatomic models using the SDFT data and employ these deep potential models to simulate large-scale systems with long trajectories.Subsequently,we compute and analyze the structural properties,dynamic properties,and transport coefficients of warm dense matter.

Resilience effects for household food expenditure and dietary diversity in rural western China

A more resilient livelihood is increasingly recognized as an efficient way to improve vulnerable households’food security and optimize their dietary decisions.This study quantifies rural household resilience in western China,identifies the three pillars(absorptive capacity,adaptive capacity,and transformative capacity)contribution to resilience,and then establishes the estimated Resilience Capacity Index(RCI)linked with food security and dietary diversity supported by the multiple indicator multiple cause(MIMIC)model.Results show that,despite geographical heterogeneity,the RCI consistently increased from 2015 to 2021.Households with a higher RCI inheriting better capacity to deal with risk and shocks are significantly and positively correlated with increasing food expenditure and diversifying food choices.It can be because resilient households will allocate more money to food expenditure instead of saving for livelihood uncertainty.Thus,policymakers can provide more incentives for rural households to adopt more dynamic and effective risk management strategies.This,in turn,could yield positive spillover effects by preventing human capital loss associated with dietary-related chronic diseases and mortality.

Tailoring MXene Thickness and Functionalization for Enhanced Room‑Temperature Trace NO_(2) Sensing

In this study,precise control over the thickness and termination of Ti3C2TX MXene flakes is achieved to enhance their electrical properties,environmental stability,and gas-sensing performance.Utilizing a hybrid method involving high-pressure processing,stirring,and immiscible solutions,sub-100 nm MXene flake thickness is achieved within the MXene film on the Si-wafer.Functionalization control is achieved by defunctionalizing MXene at 650℃ under vacuum and H2 gas in a CVD furnace,followed by refunctionalization with iodine and bromine vaporization from a bubbler attached to the CVD.Notably,the introduction of iodine,which has a larger atomic size,lower electronegativity,reduce shielding effect,and lower hydrophilicity(contact angle:99°),profoundly affecting MXene.It improves the surface area(36.2 cm^(2) g^(-1)),oxidation stability in aqueous/ambient environments(21 days/80 days),and film conductivity(749 S m^(-1)).Additionally,it significantly enhances the gas-sensing performance,including the sensitivity(0.1119Ωppm^(-1)),response(0.2% and 23%to 50 ppb and 200 ppm NO_(2)),and response/recovery times(90/100 s).The reduced shielding effect of the–I-terminals and the metallic characteristics of MXene enhance the selectivity of I-MXene toward NO2.This approach paves the way for the development of stable and high-performance gas-sensing two-dimensional materials with promising prospects for future studies.

Functional biomaterials for modulating the dysfunctional pathological microenvironment of spinal cord injury

Spinal cord injury(SCI)often results in irreversible loss of sensory and motor functions,and most SCIs are incurable with current medical practice.One of the hardest challenges in treating SCI is the development of a dysfunctional pathological microenvironment,which mainly comprises excessive inflammation,deposition of inhibitory molecules,neurotrophic factor deprivation,glial scar formation,and imbalance of vascular function.To overcome this challenge,implantation of functional biomaterials at the injury site has been regarded as a potential treatment for modulating the dysfunctional microenvironment to support axon regeneration,remyelination at injury site,and functional recovery after SCI.This review summarizes characteristics of dysfunctional pathological microenvironment and recent advances in biomaterials as well as the technologies used to modulate inflammatory microenvironment,regulate inhibitory microenvironment,and reshape revascularization microenvironment.Moreover,technological limitations,challenges,and future prospects of functional biomaterials to promote efficient repair of SCI are also discussed.This review will aid further understanding and development of functional biomaterials to regulate pathological SCI microenvironment.

Repositioning fertilizer manufacturing subsidies for improving food security and reducing greenhouse gas emissions in China

China removed fertilizer manufacturing subsidies from 2015 to 2018 to bolster market-oriented reforms and foster environmentally sustainable practices.However,the impact of this policy reform on food security and the environment remains inadequately evaluated.Moreover,although green and low-carbon technologies offer environmental advantages,their widespread adoption is hindered by prohibitively high costs.This study analyzes the impact of removing fertilizer manufacturing subsidies and explores the potential feasibility of redirecting fertilizer manufacturing subsidies to invest in the diffusion of these technologies.Utilizing the China Agricultural University Agri-food Systems model,we analyzed the potential for achieving mutually beneficial outcomes regarding food security and environmental sustainability.The findings indicate that removing fertilizer manufacturing subsidies has reduced greenhouse gas(GHG)emissions from agricultural activities by 3.88 million metric tons,with minimal impact on food production.Redirecting fertilizer manufacturing subsidies to invest in green and low-carbon technologies,including slow and controlled-release fertilizer,organic-inorganic compound fertilizers,and machine deep placement of fertilizer,emerges as a strategy to concurrently curtail GHG emissions,ensure food security,and secure robust economic returns.Finally,we propose a comprehensive set of government interventions,including subsidies,field guidance,and improved extension systems,to promote the widespread adoption of these technologies.

Women’s empowerment and food consumption:Evidence from female-headed households in Tanzania

Despite the growing recognition of women’s increasing role in the household and corresponding empowerment programs in sub-Saharan Africa,intensive research on the relationship between women’s influence and household food consumption is minimal.Using the most recent(2017-2018)national household survey data from Tanzania,this study examined the influence of women’s empowerment on household food consumption.First,we compared the monthly consumption of eight food categories between female-headed households(FHHs)and male-headed households(MHHs)using both descriptive statistics and the propensity score matching(PSM)method.Furthermore,we adopted the two-stage Linear Expenditure System and Almost Ideal Demand System model(LES-AIDS)to estimate income and price elasticities for the two household types.The results show that FHHs consume bread and cereals,fish,oils and fats,vegetables,and confectionery(sugar,jam,honey,chocolate,etc.)more than MHHs.Moreover,FHHs have a significantly higher income elasticity of demand for all food groups than MHHs.They are also more price elastic than MHHs in meat,fish,oils,fats,sugar,jam,honey,chocolate,etc.

Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis,while patients with H.pylori infection were at lower risk.IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H.pylori infection;however,metabolic syndrome increased the risk of patients with H.pylori infection developing reflux esophagitis.

Combined Promoting Effects of Specific Organic Functional Groups and Alumina Surface Characteristics for the Design of a Highly Efficient NiMo/Al_(2)O_(3) Hydrodesulfurization Catalyst

To prepare a highly efficient NiMo/Al_(2)O_(3) hydrodesulfurization catalyst,the combined effects of specific organic functional groups and alumina surface characteristics were investigated.First,the correlation between the surface characteristics of four different alumina and the existing Mo species states was established.It was found that the Mo equilibrium adsorption capacity can be used as a specific descriptor to quantitatively evaluate the changes in surface characteristics of different alumina.A lower Mo equilibrium adsorption capacity for alumina means weaker metal-support interaction and the loaded Mo species are easier to transform into MoS2.However,the Mo-O-Al bonds still exist at the metal-support interface.The introduction of cationic surfactant hecadecyl trimethyl ammonium bromide(CTAB)can further improve Mo species dispersion through electrostatic attraction with Mo anions and interaction of its alkyl chain with the alumina surface;meanwhile,the introduction of ethylenediamine tetraacetic acid(EDTA)can complex with Ni ions to enhance the Ni-promoting effect on Mo.Therefore,the NiMo catalyst designed using alumina with lower Mo equilibrium adsorption capacity and the simultaneous addition of EDTA and CTAB exhibits the highest hydrodesulfurization activity for 4,6-dimethyl dibenzothiophene because of its proper metal-support interaction and more well-dispersed Ni-Mo-S active phases.

Amino-functionalized UiO-66-doped mixed matrix membranes with high permeation performance and fouling resistance

For the reduction of bovine serum proteins from wastewater,a novel mixed matrix membrane was prepared by functionalizing the substrate material polyaryletherketone(PAEK),followed by carboxyl groups(C-SPAEKS),and then adding amino-functionalized UiO-66-NH_(2)(Am-UiO-66-NH_(2)).Aminofunctionalization of UiO-66 was accomplished by melamine,followed by an amidation reaction to immobilize Am-UiO-66-NH_(2),which was immobilized on the surface of the membrane as well as in the pore channels,which enhanced the hydrophilicity of the membrane surface while increasing the negative potential of the membrane surface.This nanoparticle-loaded ultrafiltration membrane has good permeation performance,with a pure water flux of up to 482.3 L·m^(-2)·h^(-1) for C-SPAEKS/AmUiO-66-NH_(2) and a retention rate of up to 98.7%for bovine serum albumin(BSA)-contaminated solutions.Meanwhile,after several hydrophilic modifications,the flux recovery of BSA contaminants by this series of membranes increased from 56.2%to 80.55%of pure membranes.The results of ultra-filtration flux time tests performed at room temperature showed that the series of ultrafiltration membranes remained relatively stable over a test time of 300 min.Thus,the newly developed mixed matrix membrane showed potential for high efficiency and stability in wastewater treatment containing bovine serum proteins.

Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.