Zinc concentration and bioavailability of Chinese steamed bread prepared from foliar zinc-biofortified wheat grain.

BACKGROUND: Increasing the concentration of zinc (Zn) in a widely consumed staple food, such as Chinese steamed bread (CSB), is a promising strategy for alleviating Zn malnutrition in humans. The aim of this study, which was based on a 2-year field experiment, was to evaluate the effectiveness of spraying Zn fertilizer combined with commonly applied (i) pesticides and/or (ii) KH2 PO4 (PK) to increase the concentration of Zn and its bioavailability in wheat grain and the CSB derived from it. RESULTS: All the foliar Zn applications (foliar Zn alone or combined with pesticides and PK) significantly increased the concentration of Zn in grain and derived CSB by 69.1% and 63.1%, respectively. Milling caused an 86-88% loss of Zn, while the process of producing CSB caused an 11-26% increase in the concentration of Zn. A net gain of 2.5-8.3 mg Zn kg-1 of CSB was achieved owing to foliar applications of Zn. The concentration of phytic acid (PA) decreased dramatically during milling (89-90%) and the production of CSB (69-72%). As a result, the Zn bioavailability was greater in the CSB than in grain. Foliar applications of Zn also increased the estimated Zn bioavailability of CSB to be as high as 5.5-7.8 mg, which is adequate for human nutrition. Enrichment with Zn had no adverse effects on the quality of CSB. CONCLUSION: The mixture of foliar Zn with pesticides and PK represents a useful approach to improve the bioavailable Zn of CSB without altering its quality. © 2023 Society of Chemical Industry.

Core microbes closely related with the nutrients and flavor of sweet fermented oats (whole grain food) from China.

Increased attention has been given to whole grain and plant-based foods due to health concerns. Sweet fermented oats (SFOs) are such traditional fermented food from China. However, reports on their microbiota and relations with the nutrients and flavor were scarcely few, hindering their wider application. The comprehensive microbial composition, metabolic compounds and their correlations of representative SFOs from northwestern China were firstly investigated. Firmicutes predominated the microbial communities, followed by Proteobacteria. Weissella, Bacillus and Lactobacillus were dominant bacterial genera, biomarkers and core bacteria as well. GC-MS (Gas Chromatography-Mass Spectrometer) identified the metabolic compounds, among which the categories fatty acids and carboxylic acids most abundant. Eighteen chemicals showed significant differences among the five SFOs, including ethyl octanoate, neryl acetate, L-sorbose, diglycerol, cellotetraose etc. Fatty acids, carboxylic acids, amino acids, peptides, oligosaccharides, and monosaccharides were the key substances responsible for the unique flavor and rich nutrients in SFOs. The core bacteria were closely related to chemical acids, esters, flavone and alcohol. Pediococcus showed a negative correlation with 2,3-butanediol. SFOs were made in the laboratory with the core bacterial strains, obtaining a high abundance of nutrient chemicals and sensory evaluation value. The research provided a foundation for the improvement, further application and industrialization of SFOs.

Gingival mesenchymal stem cell-derived exosomes are immunosuppressive in preventing collagen-induced arthritis.

Due to the unsatisfied effects of clinical drugs used in rheumatoid arthritis (RA), investigators shifted their focus on the biotherapy. Although human gingival mesenchymal stem cells (GMSC) have the potential to be used in treating RA, GMSC-based therapy has some inevitable side effects such as immunogenicity and tumorigenicity. As one of the most important paracrine mediators, GMSC-derived exosomes (GMSC-Exo) exhibit therapeutic effects via immunomodulation in a variety of disease models, bypassing potential shortcomings of the direct use of MSCs. Furthermore, exosomes are not sensitive to freezing and thawing, and can be readily available for use. GMSC-Exo has been reported to promote tissue regeneration and wound healing, but have not been reported to be effective against autoimmune diseases. We herein compare the immunomodulatory functions of GMSC-Exo and GMSC in collagen-induced arthritis (CIA) model and in vitro CD4+ T-cell co-culture model. The results show that GMSC-Exo has the same or stronger effects compared with GMSC in inhibiting IL-17A and promoting IL-10, reducing incidences and bone erosion of arthritis, via inhibiting IL-17RA-Act1-TRAF6-NF-κB signal pathway. Our results suggest that GMSC-Exo has many advantages in treating CIA, and may offer a promising new cell-free therapy strategy for RA and other autoimmune diseases.

Recombinant CD300c-Ig fusion protein attenuates collagen-induced arthritis in mice.

OBJECTIVES: RA is a chronic autoimmune disease characterized by joint inflammation and tissue destruction. Immune responses mediated by T cells and autoantibodies are known to play critical roles in RA. Collagen type II (CII)-induced arthritis (CIA) is a commonly used animal model of human RA. We have previously reported the identification of a new T cell inhibitory molecule CD300c. Here we investigate the ability of recombinant CD300c-IgG2a Fc (CD300c-Ig) fusion protein to prevent and treat CIA. METHODS: Mice were induced to develop CIA by CII and injected with CD300c-Ig or control Ig protein before or after CIA symptoms occur. The mice were examined for CIA clinical and pathological scores, and analysed for the expression of proinflammatory cytokines, the percentage and activation of CD4 T cells and regulatory T cells, CII-specific T cell proliferation and cytokine production, and CII-specific autoantibody production. RESULTS: In a prevention model, CD300c-Ig significantly decreases CIA incidence, and reduces clinical and pathological arthritis scores. In the treatment model, CD300c-Ig ameliorates established CIA. The beneficial effects of CD300c-Ig are related to decreased expansion and activation of T cells in the spleen and reduced expression of proinflammatory cytokines in the joints. CD300c-Ig also inhibits CII-specific T cell proliferation and Th1 and Th17 cytokine production. In addition, CD300c-Ig treatment reduced the production of CII autoantibodies in the serum. Furthermore, CD300c-Ig inhibits the proliferation and activation of T cells from RA patients in vitro. CONCLUSION: CD300c-Ig protein has the potential to be used in the treatment of patients with RA.

Skint8, a Novel B7 Family-Related Molecule, Negatively Regulates T Cell Responses.

Immune responses are tightly controlled by T cell costimulatory and coinhibitory molecules. In this study, we identify Skint8 as a new member of the T cell coinhibitory group, whose extracellular domains share significant homology with existing B7 family members. Skint8 mRNA is expressed in resting and activated B cells, monocytes, and CD4 T cells. The Skint8 putative receptor is expressed on activated CD4 and CD8 T cells, B cells, monocytes and dendritic cells. Recombinant Skint8-IgG Fc fusion protein inhibits T cell proliferation, activation, and cytokine production in vitro. In vivo administration of Skint8-IgG Fc reduces T cell activation and alleviates experimental autoimmune encephalomyelitis in mice. The findings broaden our understanding of the regulation of immune responses and may have implications for treating immune-related diseases.

Atractylodin attenuates the expression of MUC5AC and extracellular matrix in lipopolysaccharide-induced airway inflammation by inhibiting the NF-κB pathway.

This study aimed to explore the effects of atractylodin (ATR) on lipopolysaccharide (LPS)-induced inflammatory response in human airway epithelial cells. The cytotoxicity was assessed by CCK-8 assay. The mRNA expression and concentration of interleukin (IL)-6, IL-8, and mucin 5AC (MUC5AC) were measured by qRT-PCR and ELISA, respectively. Western blotting was performed to determine protein expression. We found that LPS stimulation increased the mRNA expression and concentrations of IL-6, IL-8, and MUC5AC, as well as the expression of Col-I and FN in 16HBE cells, but this effect of LPS was attenuated by ATR treatment. Mechanistically, ATR suppressed LPS-induced activation of the NF-κB pathway in 16HBE cells. Moreover, ATR repressed ovalbumin-induced airway inflammation and NF-kB pathway in mice. In conclusion, ATR attenuated the expression of MUC5AC and ECM in LPS-induced airway inflammation by inhibiting the NF-κB pathway.

Effects of long-term straw return on soil organic carbon storage and sequestration rate in North China upland crops: A meta-analysis.

Soil organic carbon (SOC) is essential for soil fertility and climate change mitigation, and carbon can be sequestered in soil through proper soil management, including straw return. However, results of studies of long-term straw return on SOC are contradictory and increasing SOC stocks in upland soils is challenging. This study of North China upland agricultural fields quantified the effects of several fertilizer and straw return treatments on SOC storage changes and crop yields, considering different cropping duration periods, soil types, and cropping systems to establish the relationships of SOC sequestration rates with initial SOC stocks and annual straw C inputs. Our meta-analysis using long-term field experiments showed that SOC stock responses to straw return were greater than that of mineral fertilizers alone. Black soils with higher initial SOC stocks also had lower SOC stock increases than did soils with lower initial SOC stocks (fluvo-aquic and loessial soils) following applications of nitrogen-phosphorous-potassium (NPK) fertilizer and NPK+S (straw). Soil C stocks under the NPK and NPK+S treatments increased in the more-than-20-year duration period, while significant SOC stock increases in the NP and NP+S treatment groups were limited to the 11- to 20-year period. Annual crop productivity was higher in double-cropped wheat and maize under all fertilization treatments, including control (no fertilization), than in the single-crop systems (wheat or maize). Also, the annual soil sequestration rates and annual straw C inputs of the treatments with straw return (NP+S and NPK+S) were significantly positively related. Moreover, initial SOC stocks and SOC sequestration rates of those treatments were highly negatively correlated. Thus, long-term straw return integrated with mineral fertilization in upland wheat and maize croplands leads to increased crop yields and SOC stocks. However, those effects of straw return are highly dependent on fertilizer management, cropping system, soil type, duration period, and the initial SOC content.

An Interpenetrating Alginate/Gelatin Network for Three-Dimensional (3D) Cell Cultures and Organ Bioprinting.

Crosslinking is an effective way to improve the physiochemical and biochemical properties of hydrogels. In this study, we describe an interpenetrating polymer network (IPN) of alginate/gelatin hydrogels (i.e., A-G-IPN) in which cells can be encapsulated for in vitro three-dimensional (3D) cultures and organ bioprinting. A double crosslinking model, i.e., using Ca2+ to crosslink alginate molecules and transglutaminase (TG) to crosslink gelatin molecules, is exploited to improve the physiochemical, such as water holding capacity, hardness and structural integrity, and biochemical properties, such as cytocompatibility, of the alginate/gelatin hydrogels. For the sake of convenience, the individual ionic (i.e., only treatment with Ca2+) or enzymatic (i.e., only treatment with TG) crosslinked alginate/gelatin hydrogels are referred as alginate-semi-IPN (i.e., A-semi-IPN) or gelatin-semi-IPN (i.e., G-semi-IPN), respectively. Tunable physiochemical and biochemical properties of the hydrogels have been obtained by changing the crosslinking sequences and polymer concentrations. Cytocompatibilities of the obtained hydrogels are evaluated through in vitro 3D cell cultures and bioprinting. The double crosslinked A-G-IPN hydrogel is a promising candidate for a wide range of biomedical applications, including bioartificial organ manufacturing, high-throughput drug screening, and pathological mechanism analyses.

In vivo administration of recombinant BTNL2-Fc fusion protein ameliorates graft-versus-host disease in mice.

Although hematopoietic stem cell transplantation (HSCT) has been widely used in the treatment of many diseases, graft-versus-host disease (GVHD) remains a major complication after allogeneic HSCT. Butyrophilin-like 2 (BTNL2) protein has been reported to have the ability to inhibit T cell proliferation in vitro; its ability to inhibit T cell responses in vivo has not been determined. We show here that in vivo administration of recombinant BTNL2-IgG2a Fc (rBTNL2-Ig) fusion protein ameliorates GVHD in mice. This is related to the ability of rBTNL2-Ig to inhibit T cell proliferation, activation and Th1/Th17 cytokine production in vivo. Furthermore, rBTNL2-Ig treatment increases the generation of regulatory T cells. Our results suggest that rBTNL2-Ig has the potential to be used in the prevention and treatment of patients with GVHD.

ESC-derived thymic epithelial cells expressing MOG prevents EAE by central and peripheral tolerance mechanisms.

Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis (MS), and is induced by immunization with disease-causative self-antigens such as myelin oligodendrocyte glycoprotein (MOG). We have previously reported that transplantation of MOG expressing thymic epithelial progenitors (TEPs) derived from 129S6SvEv Tac mouse embryonic stem cells (mESCs) prevented the development of EAE. In this study, we expand our previous studies to show that transplantation of MOG expressing mESC-TEPs derived from C57BL/6 mice also prevents EAE development. Furthermore, by using a MOG-specific T cell receptor (TCR) transgenic mouse model, we demonstrate that both central and peripheral tolerances are involved in the prevention of EAE induced by MOG expressing mESC-TEPs. Our results suggest that transplantation of human ESC-TEPs expressing MOG may provide an effective approach for the induction of MOG-specific immune tolerance, thereby the prevention and treatment of MS.

Application of ZnSO4 or Zn-EDTA fertilizer to a calcareous soil: Zn diffusion in soil and its uptake by wheat plants.

BACKGROUND: The objective of this study was to compare the efficiency of two Zn sources and two application methods on (i) Zn diffusion from fertilized soil to unfertilized soil, (ii) grain Zn concentration and (iii) grain Zn bio-accessibility to humans. In the laboratory experiment, 20 mg ZnSO4 or 4 mg Zn-EDTA were applied to a 5 mm and 1 mm-wide space in the soil in the half-cell technique. In the greenhouse experiment, Zn-ZnSO4 or Zn-ethylenediaminetetraacetic acid (Zn-EDTA) was mixed or banded with the soil at a rate of 20 or 4 mg Zn kg(-1) , respectively. RESULTS: The results from the diffusion experiment showed that both the extractability and the diffusion coefficient of Zn were higher when Zn fertilizer was applied to a 1 mm-wide space than when it was applied to a 5 mm-wide space. Zn-EDTA had a greater diffusion distance than ZnSO4 . The greenhouse experiment showed that the mixed ZnSO4 application and the Zn-EDTA application (both mixed and banded) treatments significantly increased grain Zn concentration and bio-accessibility. The positive effect of Zn-EDTA on grain Zn concentrations and bio-accessibility was greater than that of ZnSO4 . The banded application reduced the effectiveness of ZnSO4 but not of Zn-EDTA. CONCLUSION: It was concluded that Zn-EDTA was a better Zn source than ZnSO4 for increasing grain Zn content in a potentially Zn-deficient calcareous soil.

Relationship of short-term blood pressure variability with carotid intima-media thickness in hypertensive patients.

BACKGROUND: High blood pressure (BP) is among significant risk factor for stroke and other vascular occurrences, it experiences nonstop fluctuations over time as a result of a complex interface among cardiovascular control mechanisms. Large blood pressure variability (BPV) has been proved to be promising in providing potential regulatory mechanisms of the cardiovascular system. Although the previous studies also showed that BPV is associated with increased carotid intima-media thickness (IMT) and plaque, whether the correlation between variability in blood pressure and left common carotid artery-intima-media thickness (LCCA-IMT) is stronger than right common carotid artery-intima-media thickness (RCCA-IMT) remains uncertain in hypertension. METHODS: We conduct a study (78 hypertensive subjects, aged 28-79) to evaluate the relationship between BPV and carotid intima-media thickness in Shenzhen. The blood pressure was collected using the 24 h ambulatory blood pressure monitoring, and its variability was evaluated using standard deviation (SD), coefficient of variation (CV), and average real variability (ARV) during 24 h, daytime and nighttime. All the IMT measurements are collected by ultrasound. RESULTS: As the results showed, 24 h systolic blood pressure variability (SBPV) evaluated by SD and ARV were significantly related to LCCA-IMT (r(1) = 0.261, P = 0.021; r(1) = 0.262, P = 0.021, resp.). For the daytime diastolic blood pressure variability (DBPV), ARV indices were significantly related to LCCA-IMT (r(1) = 0.239, P = 0.035), which differed form BPV evaluated by SD and CV. For the night time, there is no significant correlation between the BPV and IMT. Moreover, for all the subjects, there is no significant correlation between the BPV and RCCA-IMT/number of plaques, whereas, the SD, CV, and ARV of daytime SBP showed a positive correlation with LCCA-IMT (r(1) = 0.312, P = 0.005; r(1) = 0.255, P = 0.024; r(1) = 0.284, P = 0.012, resp.). Moreover, the ARV of daytime SBPV, 24 h SBPV and nighttime DBPV showed a positive correlation with the number of plaques of LCCA (r(1) = 0.356, P = 0.008; r(1) = 0.297, P = 0.027; r(1) = 0.278, P = 0.040, resp.). In addition, the number of plaques in LCCA had higher correlation with pulse pressure and diastolic blood pressure than that in RCCA. And multiple regression analysis indicated LCCA-IMT might not only be influenced by age or smoking but also by the SD index of daytime SBPV (p = 0.035). CONCLUSIONS: The results show that SBPV during daytime and 24 h had significant correlation with IMT, for the hypertensive subjects from the southern area of China. Moreover, we also found the daytime SBPV to be the best predictor for the progression of IMT in multivariate regression analysis. In addition, the present study suggests that the correlation between BPV and left common carotid artery-intima-media thickness/number of plaques is stronger than right common carotid artery-intima-media thickness/number of plaques.

A numerical study of the effect of varied blood pressure on the stability of carotid atherosclerotic plaque.

BACKGROUND: Blood pressure (BP) is associated with early atherosclerosis and plaque rupture because the BP variability can significantly affect the blood flow velocity and shear stress over the plaque. However, the mechanical response of BP variability to the plaque remains unclear. Therefore, we investigated the correlation between different maximum systolic blood pressure (SBP) and the stress distribution on plaque, as well as the stress over the plaque and blood velocity around the plaque using different BP variations, which are the BP variability in different phases during one cardiac cycle and beat-to-beat BP variability. METHOD: We established a two-dimensional artery model with stenosis at the degree of 62.5%. Eight combinations of pulsatile pressure gradients between the inflow and outflow were implemented at the model. Three levels of fibrous cap thickness were taken into consideration to investigate the additional effect on the BP variability. Wall shear stress and stress/strain distribution over the plaque were derived as well as the oscillation shear index (OSI) to analyze the impact of the changing rate of BP. RESULT: The stresses at diastole were 2.5% ± 1.8% lower than that at systole under the same pressure drop during one cycle. It was also found that elevated SBP might cause the immediate increment of stress in the present cycle (292% ± 72.3%), but slight reduction in the successive cycle (0.48% ± 0.4%). CONCLUSION: The stress/strain distribution over the plaque is sensitive to the BP variability during one cardiac cycle, and the beat-to-beat BP variability could cause considerable impact on the progression of atherosclerosis in long-term.

Comparison of soil and foliar zinc application for enhancing grain zinc content of wheat when grown on potentially zinc-deficient calcareous soils.

BACKGROUND: The concentration of Zn and phytic acid in wheat grain has important implications for human health. We conducted field and greenhouse experiments to compare the efficacy of soil and foliar Zn fertilisation in improving grain Zn concentration and bioavailability in wheat (Triticum aestivum L.) grain grown on potentially Zn-deficient calcareous soil. RESULTS: Results from the 2-year field experiment indicated that soil Zn application increased soil DTPA-Zn by an average of 174%, but had no significant effect on grain Zn concentration. In contrast, foliar Zn application increased grain Zn concentration by an average of 61%, and Zn bioavailability by an average of 36%. Soil DTPA-Zn concentrations varied depending on wheat cultivars. There were also significant differences in grain phytic acid concentration among the cultivars. A laboratory experiment indicated that Zn (from ZnSO4 ) had a low diffusion coefficient in this calcareous soil. CONCLUSION: Compared to soil Zn application, foliar Zn application is more effective in improving grain Zn content of wheat grown in potentially Zn-deficient calcareous soils.

Enhancing neuroinduction activity of PLCL-based nerve conduits through native epineurium integration.

Autologous nerve grafts have been considered the gold standard for peripheral nerve grafts. However, due to drawbacks such as functional loss in the donor area and a shortage of donor sources, nerve conduits are increasingly being considered as an alternative approach. Polymer materials have been widely studied as nerve repair materials due to their excellent processing performance. However, their limited biocompatibility has restricted further clinical applications. The epineurium is a natural extra-neural wrapping structure. After undergoing decellularization, the epineurium not only reduces immune rejection but also retains certain bioactive components. In this study, decellularized epineurium (DEP) derived from the sciatic nerve of mammals was prepared, and a bilayer nerve conduit was created by electrospinning a poly (l-lactide-co-ε-caprolactone) (PLCL) membrane layer onto the outer surface of the DEP. Components of the DEP were examined; the physical properties and biosafety of the bilayer nerve conduit were evaluated; and the functionality of the nerve conduit was evaluated in rats. The results demonstrate that the developed bilayer nerve conduit exhibits excellent biocompatibility and mechanical properties. Furthermore, this bilayer nerve conduit shows significantly superior therapeutic effects for sciatic nerve defects in rats compared to the pure PLCL nerve conduit. In conclusion, this research provides a novel strategy for the design of nerve regeneration materials and holds promising potential for further clinical translation.

Preparation and evaluation of decellularized epineurium as an anti-adhesive biofilm in peripheral nerve repair.

Following peripheral nerve anastomosis, the anastomotic site is prone to adhesions with surrounding tissues, consequently impacting the effectiveness of nerve repair. This study explores the development and efficacy of a decellularized epineurium as an anti-adhesive biofilm in peripheral nerve repair. Firstly, the entire epineurium was extracted from fresh porcine sciatic nerves, followed by a decellularization process. The decellularization efficiency was then thoroughly assessed. Subsequently, the decellularized epineurium underwent proteomic analysis to determine the remaining bioactive components. To ensure biosafety, the decellularized epineurium underwent cytotoxicity assays, hemolysis tests, cell affinity assays, and assessments of the immune response following subcutaneous implantation. Finally, the functionality of the biofilm was determined using a sciatic nerve transection and anastomosis model in rats. The result indicated that the decellularization process effectively removed cellular components from the epineurium while preserving a number of bioactive molecules, and this decellularized epineurium was effective in preventing adhesion while promoting nerve repairment and functional recovery. In conclusion, the decellularized epineurium represents a novel and promising anti-adhesion biofilm for enhancing surgical outcomes of peripheral nerve repair.

Current Strategies for Promoting the Large-scale Production of Exosomes.

Exosomes, as nanoscale biological vesicles, have been shown to have great potential for biomedical applications. However, the low yield of exosomes limits their application. In this review, we focus on methods to increase exosome yield. Two main strategies are used to increase exosome production, one is based on genetic manipulation of the exosome biogenesis and release pathway, and the other is by pretreating parent cells, changing the culture method or adding different components to the medium. By applying these strategies, exosomes can be produced on a large scale to facilitate their practical application in the clinic.

A NRF2 inhibitor selectively sensitizes KEAP1 mutant tumor cells to cisplatin and gefitinib by restoring NRF2-inhibitory function of KEAP1 mutants.

NRF2 (nuclear factor erythroid 2-related factor 2) is a master regulator of protective responses in healthy tissues. However, when it is active in tumor cells, it can result in drug resistance. KEAP1, the endogenous NRF2 inhibitor, binds NRF2 and redirects it to proteasomal degradation, so the KEAP1/NRF2 interaction is critical for maintaining NRF2 at a basal level. A number of clinically relevant KEAP1 mutations were shown to disrupt this critical KEAP1/NRF2 interaction, leading to elevated NRF2 levels and drug resistance. Here, we describe a small-molecule NRF2 inhibitor, R16, that selectively binds KEAP1 mutants and restores their NRF2-inhibitory function by repairing the disrupted KEAP1/NRF2 interactions. R16 substantially sensitizes KEAP1-mutated tumor cells to cisplatin and gefitinib, but does not do so for wild-type KEAP1 cells, and sensitizes KEAP1 G333C-mutated xenograft to cisplatin. We developed a BRET2-based biosensor system to detect the KEAP1/NRF2 interaction and classify KEAP1 mutations. This strategy would identify drug-resistant KEAP1 somatic mutations in clinical molecular profiling of tumors.

Nerve ECM and PLA-PCL based electrospun bilayer nerve conduit for nerve regeneration.

Introduction: The porcine nerve-derived extracellular matrix (ECM) fabricated as films has good performance in peripheral nerve regeneration. However, when constructed as conduits to bridge nerve defects, ECM lacks sufficient mechanical strength. Methods: In this study, a novel electrospun bilayer-structured nerve conduit (BNC) with outer poly (L-lactic acid-co-ε-caprolactone) (PLA-PCL) and inner ECM was fabricated for nerve regeneration. The composition, structure, and mechanical strength of BNC were characterized. Then BNC biosafety was evaluated by cytotoxicity, subcutaneous implantation, and cell affinity tests. Furthermore, BNC was used to bridge 10-mm rat sciatic nerve defect, and nerve functional recovery was assessed by walking track, electrophysiology, and histomorphology analyses. Results: Our results demonstrate that BNC has a network of nanofibers and retains some bioactive molecules, including collagen I, collagen IV, laminin, fibronectin, glycosaminoglycans, nerve growth factor, and brain-derived neurotrophic factor. Biomechanical analysis proves that PLA-PCL improves the BNC mechanical properties, compared with single ECM conduit (ENC). The functional evaluation of in vivo results indicated that BNC is more effective in nerve regeneration than PLA-PCL conduit or ENC. Discussion: In conclusion, BNC not only retains the good biocompatibility and bioactivity of ECM, but also obtains the appropriate mechanical strength from PLA-PCL, which has great potential for clinical repair of nerve defects.

Interleukin-17A in Alzheimer's Disease: Recent Advances and Controversies.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that mainly affects older adults. Although the global burden of AD is increasing year by year, the causes of AD remain largely unknown. Numerous basic and clinical studies have shown that interleukin-17A (IL-17A) may play a significant role in the pathogenesis of AD. A comprehensive assessment of the role of IL-17A in AD would benefit the diagnosis, understanding of etiology and treatment. However, over the past decade, controversies remain regarding the expression level and role of IL-17A in AD. We have incorporated newly published researches and point out that IL-17A expression levels may vary along with the development of AD, exercising different roles at different stages of AD, although much more work remains to be done to support the potential role of IL-17A in AD-related pathology. Here, it is our intention to review the underlying mechanisms of IL-17A in AD and address the current controversies in an effort to clarify the results of existing research and suggest future studies.