Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis.

MAPK pathway-driven tumorigenesis, often induced by BRAFV600E, relies on epithelial dedifferentiation. However, how lineage differentiation events are reprogrammed remains unexplored. Here, we demonstrate that proteostatic reactivation of developmental factor, TBX3, accounts for BRAF/MAPK-mediated dedifferentiation and tumorigenesis. During embryonic development, BRAF/MAPK upregulates USP15 to stabilize TBX3, which orchestrates organogenesis by restraining differentiation. The USP15-TBX3 axis is reactivated during tumorigenesis, and Usp15 knockout prohibits BRAFV600E-driven tumor development in a Tbx3-dependent manner. Deleting Tbx3 or Usp15 leads to tumor redifferentiation, which parallels their overdifferentiation tendency during development, exemplified by disrupted thyroid folliculogenesis and elevated differentiation factors such as Tpo, Nis, Tg. The clinical relevance is highlighted in that both USP15 and TBX3 highly correlates with BRAFV600E signature and poor tumor prognosis. Thus, USP15 stabilized TBX3 represents a critical proteostatic mechanism downstream of BRAF/MAPK-directed developmental homeostasis and pathological transformation, supporting that tumorigenesis largely relies on epithelial dedifferentiation achieved via embryonic regulatory program reinitiation.

Behaviors and Mechanisms of Adsorption of MB and Cr(VI) by Geopolymer Microspheres under Single and Binary Systems.

Geopolymers show great potential in complex wastewater treatment to improve water quality. In this work, general geopolymers, porous geopolymers and geopolymer microspheres were prepared by the suspension curing method using three solid waste products, coal gangue, fly ash and blast furnace slag. The microstructure, morphology and surface functional groups of the geopolymers were studied by SEM, XRD, XRF, MIP, FTIR and XPS. It was found that the geopolymers possess good adsorption capacities for both organic and inorganic pollutants. With methylene blue and potassium dichromate as the representative pollutants, in order to obtain the best removal rate, the effects of the adsorbent type, dosage of adsorbent, concentration of methylene blue and potassium dichromate and pH on the adsorption process were studied in detail. The results showed that the adsorption efficiency of the geopolymers for methylene blue and potassium dichromate was in the order of general geopolymers < porous geopolymers < geopolymer microspheres, and the removal rates were up to 94.56% and 79.46%, respectively. Additionally, the competitive adsorption of methylene blue and potassium dichromate in a binary system was also studied. The mechanism study showed that the adsorption of methylene blue was mainly through pore diffusion, hydrogen bond formation and electrostatic adsorption, and the adsorption of potassium dichromate was mainly through pore diffusion and redox reaction. These findings demonstrate the potential of geopolymer microspheres in adsorbing organic and inorganic pollutants, and, through five cycles of experiments, it is demonstrated that MGP exhibits excellent recyclability.

Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medications.

Background: Previous studies have shown that the rs717620 polymorphism in ABCC2, the gene encoding multidrug resistance protein 2, influences the therapeutic response to anti-seizure medications (ASMs). However, this result is not consistent, and the mechanism by which rs717620 influences ASM responses is unclear. Aims: The present study evaluated the association between rs717620 genotype and ASM efficacy, and examined the potential mechanisms. Main: methods: We conducted a literature search of five electronic databases, Embase, Medline, Web of Science, China National Knowledge Infrastructure, and Wanfang, to identify relevant studies on response to ASM therapy among rs717620 genotypes. Expression quantitative trait loci analysis and drug-gene interaction analysis were also performed to assess the underlying mechanisms. Key findings: The pooled results for 18 studies revealed a significant association between rs717620 genotype and ASM resistance under the recessive model (TT vs. CT + CC: OR = 1.68, 95 % CI = 1.27-2.21, I2 = 3.1 %). A significant association was also found in the Asian population under the recessive model (TT vs. CT + CC: OR = 1.70, 95 % CI = 1.26-2.29, I2 = 29.3 %). Further analysis revealed that rs717620 regulates the expression of ABCC2 in human brain, while drug-gene interaction analysis suggested that ABCC2 interacts with oxcarbazepine and carbamazepine. Significance: The rs717620 polymorphism influences ASM therapeutic responses by altering brain expression levels of ABCC2.

Identification of potential crucial genes and therapeutic targets for epilepsy.

BACKGROUND: Epilepsy, a central neurological disorder, has a complex genetic architecture. There is some evidence suggesting that genetic factors play a role in both the occurrence of epilepsy and its treatment. However, the genetic determinants of epilepsy are largely unknown. This study aimed to identify potential therapeutic targets for epilepsy. METHODS: Differentially expressed genes (DEGs) were extracted from the expression profiles of GSE44031 and GSE1834. Gene co-expression analysis was used to confirm the regulatory relationship between newly discovered epilepsy candidate genes and known epilepsy genes. Expression quantitative trait loci analysis was conducted to determine if epilepsy risk single-nucleotide polymorphisms regulate DEGs' expression in human brain tissue. Finally, protein-protein interaction analysis and drug-gene interaction analysis were performed to assess the role of DEGs in epilepsy treatment. RESULTS: The study found that the protein tyrosine phosphatase receptor-type O gene (PTPRO) and the growth arrest and DNA damage inducible alpha gene (GADD45A) were significantly upregulated in epileptic rats compared to controls in both datasets. Gene co-expression analysis revealed that PTPRO was co-expressed with RBP4, NDN, PAK3, FOXG1, IDS, and IDS, and GADD45A was co-expressed with LRRK2 in human brain tissue. Expression quantitative trait loci analysis suggested that epilepsy risk single-nucleotide polymorphisms could be responsible for the altered PTPRO and GADD45A expression in human brain tissue. Moreover, the protein encoded by GADD45A had a direct interaction with approved antiepileptic drug targets, and GADD45A interacts with genistein and cisplatin. CONCLUSIONS: The results of this study highlight PTPRO and GADD45A as potential genes for the diagnosis and treatment of epilepsy.

Identification of a novel ferroptosis-related gene signature associated with retinal degeneration induced by light damage in mice.

Background: Neurodegenerative retinal diseases such as retinitis pigmentosa are serious disorders that may cause irreversible visual impairment. Ferroptosis is a novel type of programmed cell death, and the involvement of ferroptosis in retinal degeneration is still unclear. This study aimed to investigate the related ferroptosis genes in a mice model of retinal degeneration induced by light damage. Methods: A public dataset of GSE10528 deriving from the Gene Expression Omnibus database was analyzed to identify the differentially expressed genes (DEGs). Gene set enrichment analysis between light damage and control group was conducted. The differentially expressed ferroptosis-related genes (DE-FRGs) were subsequently identified by intersecting the DEGs with a ferroptosis genes dataset retrieved from the FerrDb database. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were further performed using the DE-FRGs. A protein-protein interaction (PPI) network was constructed to identify hub ferroptosis-related genes (HFRGs). The microRNAs (miRNAs)-HFRGs, transcription factors (TFs)-HFRGs networks as well as target drugs potentially interacting with HFRGs were analyzed utilizing bioinformatics algorithms. Results: A total of 932 DEGs were identified between the light damage and control group. Among these, 25 genes were associated with ferroptosis. GO and KEGG analyses revealed that these DE-FRGs were mainly enriched in apoptotic signaling pathway, response to oxidative stress and autophagy, ferroptosis, necroptosis and cytosolic DNA-sensing pathway. Through PPI network analysis, six hub ferroptosis-related genes (Jun, Stat3, Hmox1, Atf3, Hspa5 and Ripk1) were ultimately identified. All of them were upregulated in light damage retinas, as verified by the GSE146176 dataset. Bioinformatics analyses predicated that 116 miRNAs, 23 TFs and several potential therapeutic compounds might interact with the identified HFRGs. Conclusion: Our study may provide novel potential biomarkers, therapeutic targets and new insights into the ferroptosis landscape in retinal neurodegenerative diseases.

Dynamical analysis of a glucose-insulin regulatory system with insulin-degrading enzyme and multiple delays.

This paper investigates the dynamics of a glucose-insulin regulatory system model that incorporates: (1) insulin-degrading enzyme in the insulin equation; and (2) discrete time delays respectively in the insulin production term, hepatic glucose production term, and the insulin-degrading enzyme. We provide rigorous results of our model including the asymptotic stability of the equilibrium solution and the existence of Hopf bifurcation. We show that analytically and numerically at a certain value the time delays driven stability or instability occurs when the corresponding model has an interior equilibrium. Moreover, we illustrate the oscillatory regulation and insulin secretion via numerical simulations, which show that the model dynamics exhibit physiological observations and more information by allowing parameters to vary. Our results may provide useful biological insights into diabetes for the glucose-insulin regulatory system model.

Comprehensive analyses identify potential biomarkers for encephalitis in HIV infection.

Human immunodeficiency virus encephalitis (HIVE) is a severe neurological complication after HIV infection. Evidence shows that genetic factors play an important role in HIVE. The aim of the present study was to identify new potential therapeutic targets for HIVE. Differentially expressed gene (DEG), functional annotation and pathway, and protein-protein interaction analyses were performed to identify the hub genes associated with HIVE. Gene co-expression analysis was carried out to confirm the association between the hub genes and HIVE. Finally, the role of the hub genes in HIVE therapy was evaluated by conducting drug-gene interaction analysis. A total of 20 overlapping DEGs closely related to HIVE were identified. Functional annotation and pathway enrichment analysis indicated that the markedly enriched DEG terms included ion transport, type II interferon signaling, and synaptic signaling. Moreover, protein-protein interaction analysis revealed that 10 key HIVE-related genes were hub genes, including SCN8A, CDK5R2, GRM5, SCN2B, IFI44L, STAT1, SLC17A7, ISG15, FGF12, and FGF13. Furthermore, six hub genes were co-expressed with HIVE-associated host genes in human brain tissue. Finally, three hub genes (STAT1, ISG15, and SCN2B) interacted with several inflammation-associated drugs. These findings suggested that SCN8A, CDK5R2, GRM5, SCN2B, IFI44L, STAT1, SLC17A7, ISG15, FGF12, and FGF13 may be new targets for diagnosis and therapy of HIVE.

Dysregulated Arginine Metabolism Is Linked to Retinal Degeneration in Cep250 Knockout Mice.

Purpose: Degeneration of retinal photoreceptors is frequently observed in diverse ciliopathy disorders, and photoreceptor cilium gates the molecular trafficking between the inner and the outer segment (OS). This study aims to generate a homozygous global Cep250 knockout (KO) mouse and study the resulting phenotype. Methods: We used Cep250 KO mice and untargeted metabolomics to uncover potential mechanisms underlying retinal degeneration. Long-term follow-up studies using optical coherence tomography (OCT) and electroretinography (ERG) were performed. Results: OCT and ERG results demonstrated gradual thinning of the outer nuclear layer (ONL) and progressive attenuation of the scotopic ERG responses in Cep250-/- mice. More TUNEL signal was observed in the ONL of these mice. Immunostaining of selected OS proteins revealed mislocalization of these proteins in the ONL of Cep250-/- mice. Interestingly, untargeted metabolomics analysis revealed arginine-related metabolic pathways were altered and enriched in Cep250-/- mice. Mis-localization of a key protein in the arginine metabolism pathway, arginase 1 (ARG1), in the ONL of KO mice further supports this model. Moreover, adeno-associated virus (AAV)-based retinal knockdown of Arg1 led to similar architectural and functional alterations in wild-type retinas. Conclusions: Altogether, these results suggest that dysregulated arginine metabolism contributes to retinal degeneration in Cep250-/- mice. Our findings provide novel insights that increase understanding of retinal degeneration in ciliopathy disorders.

Polydopamine-Coated Polycaprolactone Electrospun Nanofiber Membrane Loaded with Thrombin for Wound Hemostasis.

Hemorrhagic shock is the primary cause of death in patients with severe trauma, and the development of rapid and efficient hemostatic methods is of great significance in saving the lives of trauma patients. In this study, a polycaprolactone (PCL) nanofiber membrane was prepared by electrospinning. A PCL-PDA loading system was developed by modifying the surface of polydopamine (PDA), using inspiration from mussel adhesion protein, and the efficient and stable loading of thrombin (TB) was realized to ensure the bioactivity of TB. The new thrombin loading system overcomes the disadvantages of harsh storage conditions, poor strength, and ease of falling off, and it can use thrombin to start a rapid coagulation cascade reaction, which has the characteristics of fast hemostasis, good biocompatibility, high safety, and a wide range of hemostasis. The physicochemical properties and biocompatibility of the PCL-PDA-TB membrane were verified by scanning electron microscopy, the cell proliferation test, the cell adhesion test, and the extract cytotoxicity test. Red blood cell adhesion, platelet adhesion, dynamic coagulation time, and animal models all verified the coagulation effect of the PCL-PDA-TB membrane. Therefore, the PCL-PDA-TB membrane has great potential in wound hemostasis applications, and should be widely used in various traumatic hemostatic scenarios.

Causal effects of serum lipid biomarkers on early age-related macular degeneration using Mendelian randomization.

BACKGROUND: Age-related macular degeneration (AMD) is one of the major causes of vision loss. Early AMD needs to be taken seriously, but the causal effects of lipid biomarkers on early AMD remain unclear. METHODS: In this study, two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between seven serum lipid biomarkers (apolipoprotein A (ApoA), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], and triglycerides (TG)) and risk of early AMD. In total, 14,034 cases and 91,214 controls of European ancestry were included in the analysis (number of SNPs = 11,304,110). RESULTS: MR estimates revealed that a higher HDL-C level is strongly associated with increased risk of early AMD (OR = 1.25, 95% CI: 1.15-1.35, P = 2.61 × 10-8). In addition, level of ApoA is also positively associated with risk of early AMD (OR = 2.04, 95% CI: 1.50-2.77, P = 6.27 × 10-6). Conversely, higher levels of TG significantly decrease the risk of early AMD (OR = 0.77, 95% CI: 0.71-0.84, P = 5.02 × 10-10). Sensitivity analyses further supported these associations. Moreover, multivariable MR analyses, adjusted for the effects of correlated lipid biomarkers, yielded similar results. CONCLUSION: This study identifies causal relationships between elevated circulating HDL-C/ApoA levels and increased risk of early AMD, in addition to finding that TG specifically reduces the risk of early AMD. These findings contribute to a better understanding of the role of lipid metabolism in drusen formation, particularly in early AMD development.

Kindlin-2 controls angiogenesis through modulating Notch1 signaling.

Kindlin-2 is critical for development and homeostasis of key organs, including skeleton, liver, islet, etc., yet its role in modulating angiogenesis is unknown. Here, we report that sufficient KINDLIN-2 is extremely important for NOTCH-mediated physiological angiogenesis. The expression of KINDLIN-2 in HUVECs is significantly modulated by angiogenic factors such as vascular endothelial growth factor A or tumor necrosis factor α. A strong co-localization of CD31 and Kindlin-2 in tissue sections is demonstrated by immunofluorescence staining. Endothelial-cell-specific Kindlin-2 deletion embryos die on E10.5 due to hemorrhage caused by the impaired physiological angiogenesis. Experiments in vitro show that vascular endothelial growth factor A-induced multiple functions of endothelial cells, including migration, matrix proteolysis, morphogenesis and sprouting, are all strengthened by KINDLIN-2 overexpression and severely impaired in the absence of KINDLIN-2. Mechanistically, we demonstrate that KINDLIN-2 inhibits the release of Notch intracellular domain through binding to and maintaining the integrity of NOTCH1. The impaired angiogenesis and avascular retinas caused by KINDLIN-2 deficiency can be rescued by DAPT, an inhibitor of γ-secretase which releases the intracellular domain from NOTCH1. Moreover, we demonstrate that high glucose stimulated hyperactive angiogenesis by increasing KINDLIN-2 expression could be prevented by KINDLIN-2 knockdown, indicating Kindlin-2 as a potential therapeutic target in treatment of diabetic retinopathy. Our study for the first time demonstrates the significance of Kindlin-2 in determining Notch-mediated angiogenesis during development and highlights Kindlin-2 as the potential therapeutic target in angiogenic diseases, such as diabetic retinopathy.

Glucose-induced CRL4COP1-p53 axis amplifies glycometabolism to drive tumorigenesis.

The diabetes-cancer association remains underexplained. Here, we describe a glucose-signaling axis that reinforces glucose uptake and glycolysis to consolidate the Warburg effect and overcome tumor suppression. Specifically, glucose-dependent CK2 O-GlcNAcylation impedes its phosphorylation of CSN2, a modification required for the deneddylase CSN to sequester Cullin RING ligase 4 (CRL4). Glucose, therefore, elicits CSN-CRL4 dissociation to assemble the CRL4COP1 E3 ligase, which targets p53 to derepress glycolytic enzymes. A genetic or pharmacologic disruption of the O-GlcNAc-CK2-CSN2-CRL4COP1 axis abrogates glucose-induced p53 degradation and cancer cell proliferation. Diet-induced overnutrition upregulates the CRL4COP1-p53 axis to promote PyMT-induced mammary tumorigenesis in wild type but not in mammary-gland-specific p53 knockout mice. These effects of overnutrition are reversed by P28, an investigational peptide inhibitor of COP1-p53 interaction. Thus, glycometabolism self-amplifies via a glucose-induced post-translational modification cascade culminating in CRL4COP1-mediated p53 degradation. Such mutation-independent p53 checkpoint bypass may represent the carcinogenic origin and targetable vulnerability of hyperglycemia-driven cancer.

Suppressing Structural Relaxation in Nanoscale Antimony to Enable Ultralow-Drift Phase-Change Memory Applications.

Phase-change random-access memory (PCRAM) devices suffer from pronounced resistance drift originating from considerable structural relaxation of phase-change materials (PCMs), which hinders current developments of high-capacity memory and high-parallelism computing that both need reliable multibit programming. This work realizes that compositional simplification and geometrical miniaturization of traditional GeSbTe-like PCMs are feasible routes to suppress relaxation. While to date, the aging mechanisms of the simplest PCM, Sb, at nanoscale, have not yet been unveiled. Here, this work demonstrates that in an optimal thickness of only 4 nm, the thin Sb film can enable a precise multilevel programming with ultralow resistance drift coefficients, in a regime of ≈10-4 -10-3 . This advancement is mainly owed to the slightly changed Peierls distortion in Sb and the less-distorted octahedral-like atomic configurations across the Sb/SiO2 interfaces. This work highlights a new indispensable approach, interfacial regulation of nanoscale PCMs, for pursuing ultimately reliable resistance control in aggressively-miniaturized PCRAM devices, to boost the storage and computing efficiencies substantially.

Distribution of 50-layer corneal densitometry values and related factors.

PURPOSE: To investigate the distribution of 50 layers of corneal densitometry and related factors. METHODS: Clinical data, including age, sex, central corneal thickness, corneal keratometry, and diopters, were collected from 102 healthy participants (102 eyes) in this retrospective study. The cornea was divided into 50 layers, and densitometry of each layer at 19 points was measured by the Pentacam. The value versus the depth curve was plotted. Paired-sample t test and one-way analysis of variance were used to compare densitometry in different regions or depth. Statistical significance was defined as P < .05. RESULTS: The densitometry values of the Bowman membrane (10-14% depth), anterior stroma (14-30% depth), epithelium (0-10% depth), and Descemet membrane (94-98% depth) decreased sequentially, and the densitometry values of the middle and posterior stroma (30-94% depth) and endothelium (98-100% depth) were the lowest. The higher the degree of astigmatism, the higher the second densitometry peak (R = 0.277, P < .001). The densitometry values of the vertex and superior parts of the cornea were higher than those in the periphery and inferior parts, respectively (all P < .001). In the Bowman membrane, the densitometry is lowest in the inferior nasal part, while in the Descemet membrane, it is lowest in the inferior temporal part. CONCLUSION: Two densitometry peaks appeared near the Bowman membrane and Descemet membrane. For different depths, the distribution of densitometry within a layer is different. We provide a methodological reference and data basis for corneal research based on local changes in densitometry, and help understand the details of corneal structure from an optical perspective through detailed layering and zoning analysis of densitometry.

Nanoscale Chemical Heterogeneity Ensures Unprecedently Low Resistance Drift in Cache-Type Phase-Change Memory Materials.

Phase-change random access memory is a promising technique to realize universal memory and neuromorphic computing, where the demand for robust multibit programming drives exploration for high-accuracy resistance control in memory cells. Here in ScxSb2Te3 phase-change material films, we demonstrate thickness-independent conductance evolution, presenting an unprecedently low resistance-drift coefficient in the range of ∼10-4-10-3, ∼3-2 orders of magnitude lower compared to conventional Ge2Sb2Te5. By atom probe tomography and ab initio simulations, we unveiled that nanoscale chemical inhomogeneity and constrained Peierls distortion together suppress structural relaxation, rendering an almost invariant electronic band structure and thereby the ultralow resistance drift of ScxSb2Te3 films upon aging. Associated with subnanosecond crystallization speed, ScxSb2Te3 serves as the most appropriate candidate for developing high-accuracy cache-type computing chips.

New Set of Isobaric Labeling Reagents for Quantitative 16Plex Proteomics.

Peptide labeling by isobaric tags is a powerful approach for the relative quantitative analysis of proteomes in multiple groups. There has been a revolution in the innovation of new isobaric reagents; however, great effort is being made to expand simultaneous labeling groups to identify more labeled peptides and reduce reporter ion signal suppression. We redesigned the original chemical structure of the deuterium isobaric amine-reactive tag developed in our laboratory. We optimized the synthetic pathway to create a new set of 16-plex isobaric tags (IBT-16plex). The novel reagent enabled almost complete labeling of peptides within 90 min, with all labeling reporter ions exhibiting comparable MS/MS signals. Compared to a typical 16plex reagent, TMTpro-16plex, the peptides and proteins identified by IBT-16plex in trypsinized HeLa cells were significantly increased by 14.8 and 8.6%, respectively. Moreover, differences in peptide abundance within 10-fold among multiple groups were barely suppressed in IBT-16plex, whereas the dynamic range in TMTpro-16plex-labeled groups was smaller. After quantitative examination of MCF7 cell proteins, IBT-16plex was confirmed as feasible and useful for evaluating protein responses of glucose-starved MCF7 cells to a glucose-rich medium.

Effect of chitosan on the mechanical properties and acid resistance of metakaolin-blast furnance slag-based geopolymers.

Adding organics in the process of geopolymer synthesis can combine the functional groups of organics with the three-dimensional structure of geopolymer, thus changing the properties of geopolymer such as compressive strength, flexural strength, and acid resistance. In this work, excellent mechanical properties and acid resistance of metakaolin-blast furnance slag (Mk-BFS)-based geopolymer were synthesized by the incorporation of chitosan. The formation of sodium-alumino-silicate-hydrate (N-A-S-H) gel and calium-alumino-silicate-hydrate (C-A-S-H) gel in geopolymerization were characterized by 29Si nuclear magnetic resonance (NMR). At 5% of chitosan, the compressive strength of Mk-BFS-based geopolymer could reach to 33.7 MPa. The results could be ascribed to that chitosan reacts with geopolymer to generate new C-O-Si structure meanwhile adhesion produced by the combination of positively charged cations and negatively charged ions makes the structure of geopolymer denser. After 7 days of sulfuric acid immersion, the reduction of compressive strength is less than 3 MPa, demonstrating its great acid resistance. The acid resistance of Mk-BFS-based geopolymer could attribute to that the free amino groups in chitosan preferentially react with acid solution and weakened the erosion of sulfuric acid. This study optimizes the compressive strength and acid resistance of geopolymer by adding appropriate amount of chitosan.

Synergistic gel formation in geopolymers of superior mechanical strength synthesized with volcanic ash and slag.

The present work studies gel evolution and microstructure of geopolymers synthesized with volcanic ash (VA) and blast furnace slag (BFS). The synthesis parameters such as BFS proportions on geopolymer formation were investigated. Gel evolution and microstructure of the geopolymers were studied by FTIR, X-ray diffraction (XRD), 29Si NMR spectroscopy and scanning electron microscopy measurements. Silicate gels (N-S-H) were mainly formed in VA-based geopolymers of low compressive strength (14.07 MPa). While with VA and BFS each account for 50%, VA-BFS-based geopolymers possessed a compressive strength of 55.6 MPa, as well as the homogeneous C-(A)-S-H and N-A-S-H gels were formed. The C-(A)-S-H and N-A-S-H gels show synergistic effects on the mechanical property of the geopolymers. This work provides a clue for the synthesis of geopolymers with superior mechanical properties in areas of architecture. Detailed characterization gel evolution and microstructure of geopolymers synthesized with volcanic ash (VA) and blast furnace slag (BFS) were studied. Silicate gels (N-S-H) were mainly formed in VA-based geopolymers of low compressive strength (14.07 MPa). When VA and BFS each account for 50%, VA-BFS-based geopolymers possessed a compressive strength of 55.6 MPa, as well as the homogeneous C-(A)-S-H and N-A-S-H gels formed. Synthesis protocol for VA-BFS-based geopolymers.

Nerve growth factor-basic fibroblast growth factor poly-lactide co-glycolid sustained-release microspheres and the small gap sleeve bridging technique to repair peripheral nerve injury.

We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique. Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury; as a result, in this study, we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration. First, in an in vitro biomimetic microenvironment, we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells. We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells. The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique. Compared with epithelium sutures and small gap sleeve bridging alone, the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.