Catalytic performance and mechanism study of the isomerization of 2,5-dichlorotoluene to 2,4-dichlorotoluene.

This work investigates the influence of catalyst HZSM-5 on the isomerization of 2,5-dichlorotoluene (2,5-DCT) to produce 2,4-dichlorotoluene (2,4-DCT). We observe that hydrothermal treatment leads to a decrease in total acidity and Brønsted/Lewis ratio of HZSM-5 while generating new secondary pores. These characteristics result in excellent selectivity for post-hydrothermal modified HZSM-5 in the isomerization reaction from 2,5-DCT to 2,4-DCT. Under atmospheric pressure at 350 °C, unmodified HZSM-5 achieves a selectivity of 66.4% for producing 2,4-DCT, however after hydrothermal modification the selectivity increases to 78.7%. Density Functional Theory (DFT) calculations explore the thermodynamic aspects of adsorption between the HZSM-5 surface and 2,4-DCT. The kinetic perspective investigates the mechanism involving proton attack on the methyl group of 2,5-DCT followed by rearrangement leading to formation of 2,4-DCT during isomerization. The consistency between simulation and experimental results provides evidence for the feasibility of isomerizing 2,5-DCT to 2,4-DCT. This work fills the gap in the low value-added product 2,5-DCT isomer conversion, indicating its significant practical application potential and provides a valuable reference and guidelines for industrial research in this field.

Homogeneous base catalyst with high activity and stability for synthesis of dimethyl carbonate by transesterification.

In the synthesis of dimethyl carbonate (DMC) by transesterification, CH3ONa has been commonly applied as a homogeneous catalyst due to its high catalytic activity, but its stability is unsatisfactory. Here, by studying the influence of ionic liquid base strength on transesterification, we prepared an organic base catalyst, potassium imidazole (KIm), with high catalytic activity and stability, which solved the problem of catalyst deactivation in transesterification. The results showed that when KIm was used in the synthesis of DMC from propylene carbonate (PC) and methanol (MeOH), the chemical equilibrium could be reached within 3 minutes and the yield of DMC reached 73.03%, indicating that KIm performed better in transesterification than the majority of previously reported catalysts. In addition, the activity of the catalyst had hardly decreased after ten cycles of reaction, which can well meet the requirements of industrial production.

Photomodulation on Active Sites of Adsorbents: Controllable Adsorption Processes with Improved Efficiency.

Adsorption is a widely applied technique in producing high-purity chemicals with advantages of low energy consumption, high selectivity, and mild operating conditions. However, traditional adsorbents have inflexible properties and suffer from the trade-off between selective adsorption and efficient desorption. Recently, the emerging photoresponsive adsorbents have provided new avenues for adsorption techniques. Active sites of photoresponsive adsorbents can be regulated through steric hindrance or tunable adsorbent-adsorbate interactions. Therefore, variation in adsorptive capacity is able to readily achieve through photomodulation, and the corresponding adsorption/desorption cycles are energy-saving. This concept mainly summarizes recent efforts on the fabrication and application of photoresponsive adsorbents with tunable active sites. Also, the future opportunities and critical challenges of photoregulation on adsorptive sites are presented.

High-efficiency catalyst CuSO4/SBA-15 toward butylated hydroxytoluene synthesis in a heterogeneous system.

An SBA-15 loaded CuSO4 catalyst was designed and prepared for the highly selective production of 2,6-di-tert-butyl-p-cresol (BHT) from p-cresol and isobutylene. The acidity of solid acid catalysts was altered by varying the loading amount of CuSO4. Among them, 10% CuSO4/SBA-15 exhibited the greatest catalytic performance in the alkylation reaction with a BHT yield of 85.5%. After four cycles, the yield of BHT exceeded 70%. Overall, the catalyst has excellent catalytic performance and can be utilized as a catalyst for efficient BHT production.

Enrichment of Residual Carbon in Coal Gasification Fine Slag via Wet Sieving Separation with Ultrasonic Pretreatment.

To overcome the environmental and economic challenges posed by the increasing amounts of the coal gasification slag, here, a simple and efficient method for enriching the residual carbon from the coal gasification fine slag was proposed. The residual carbon enrichment pattern in the particle size distribution of coal gasification fine slags after the ultrasonic pretreatment was mainly enriched toward the 500-250 µm and 250-125 µm particle size classes by analyzing the changes in the particle size distribution and apparent morphology. The pulp pretreatment at the ultrasonic output power of 270 W for 4 min was determined as the optimal experimental condition with respect to the yield, ash content, and ash rejection of the concentrates. Compared to the conventional wet sieving separation, the yield and ash content of the final concentrates were reduced by 7.99 and 14.96%, respectively. Moreover, the ash rejection of the final concentrates was as high as 88.51%, indicating an increment of 11.63% than the conventional wet sieving separation. Furthermore, thermogravimetric analysis confirmed that the final concentrates exhibited the lowest reactivity; however, these demonstrated had the highest carbon content (nearly 70%) with 27.27% ash content. The combustion characteristics analysis showed that the wet screening concentrate after ultrasonic pretreatment had the highest composite combustion characteristic index (S) of 3.17 × 10-8, as compared to the raw and conventional sieving concentrates.

Functional genetic variation in 3'UTR of PARP1 indicates a decreased risk and a better severity of ischemic stroke.

Aim of the study: Polymorphisms of DNA repair enzyme gene may alter the ability of damage repair, ischemic stroke susceptibility and outcome. This study aimed to explore the association of polymorphisms in PARP1 and the effects of interactions between genes in Chinese.Materials and methods: A total of 500 patients and 500 healthy controls were enrolled for genotyping. Results: Clinical information analysis revealed higher levels of alcohol and smoking exposure in patients with ischemic stroke, as well as chronic conditions such as diabetes, hypertension, and higher serum triglycerides concentration. In addition, Polymorphism in PARP1 rs8679 was significantly associated with the decreased ischemic stroke risk. Patients harboring the PARP1 rs8679 AG/GG genotype had a better initial stroke, and as for the mRNA level of PARP1, it was suppressed with mutant genotype in comparison with the wild genotype. Finally, the suppressed of PARP1 was induced by gain-binding ability of miR-124-5p through 3'UTR directly binding.Conclusions: In conclusion, our study demonstrates that the SNP rs8679 in PARP1 3'-UTR might act as a protective factor for the outcome of patients with ischemic stroke.

Poly (Adenosine Diphosphate Ribose) Polymerase-1 Single Nucleotide Polymorphism in the 3'-Untranslated Region for Ischemic Stroke Risk Reduction.

OBJECTIVE: To determine the effect of PARP1 polymorphism on gene interactions. METHODS: A total of 500 patients and 500 healthy controls were enrolled. RESULTS: Analysis of clinical data showed that patients with stroke, diabetes, hypertension, and elevated serum triglyceride levels had higher levels of alcohol and smoking. The polymorphism of PARP1rs8679 was inversely associated with the risk of ischemic stroke. Patients with PARP1rs8679AG/ GG genotypes had a lower incidence of an initial stroke. Compared with the wild genotype, mRNA levels of PARP1 were reduced. MiR-124-5p directly induced PARP1 inhibition through the gain binding ability of 3 'UTR binding. CONCLUSION: Single nucleotide polymorphism (SNP) rs8679 in PARP13'UTR can prevent ischemic stroke.

Functional Connectivity in Parkinson's Disease Patients with Mild Cognitive Impairment.

OBJECTIVE: To explore the alteration of pattens of anatomical and functional connectivity (FC) of posterior cingulate cortex (PCC) in Parkinson's disease (PD) patients with cognitive dysfunction and the relationship between the connection strengths and cognitive state. METHODS: We prospectively enrolled 20 PD patients with mild cognitive impairment (PD-MCI), 13 PD patients with normal cognition (PD-NC) and 13 healthy controls (HCs). By collecting, preprocessing and FC analyzing resting-state functional magnetic resonance imaging (rs-fMRI) data, we extracted default mode network (DMN) patterns, compared the differences in DMN between the three groups and the analyzed the correlation between FC value with the commonly used neuropsychological testing. RESULTS: The PD-MCI showed significant worse performances in general cognition, and PD-NC and HCs showed comparable performances of cognitive function. Cognitive-related differences in DMN were detected in the bilateral precuneus (BPcu). Compared with the HCs, PD-NC and PD-MCI showed significantly decreased FC within BPcu (both P < 0.001). For PD-MCI, the rho of the Fisher's Z-transformed FC (zFC) value within BPcu with the TMTA, DSST and CFT-20min were 0.50, 0.66 and 0.47, respectively. For PD-NC, the rho of the zFC value within BPcu with the MMSE was 0.58. DISCUSSION: BPcu was the cognitive-related region in DMN. As cognition declines, FC within BPcu weakens. For PD-MCI, the higher the FC values within BPcu were likely to be related to the better the performances of TMTA, DSST and CFT-20 min DR, which needs to be further confirmed by large-sample studies.

Expression of RAB7L1 in Patients with Pituitary Adenomas.

Pituitary adenomas (PA) are neoplasms that arise predominantly in the adenohypophysis. They are generally divided into three categories depending on their biological behavior: benign adenomas, invasive adenomas, and carcinomas. They represent 10%-25% of all intracranial neoplasms, and their estimated prevalence in the general population is 17%. RAB7L1, located at the PARK16 locus, is a Rab GTPase key regulator in vesicle trafficking. Recent genome-wide association studies have linked variants in RAB7L1 to the risk of Parkinson's disease. However, the association between RAB7L1 and PAs is still unexplored. Thirty patients with pituitary adenomas who had undergone surgical resection at Jiangyin People's Hospital (Jiangsu, China) from 2014 to 2019 were selected. The RAB7L1 expression level was assessed by qPCR, Western blot, and immunohistochemical staining. The level of the RAB7L1 differential expression was closely related to the patients' age and size of the PAs. In contrast, the RAB7L1 expression level was found to be unrelated to gender, Knosp classification, or type of PA. Our study found that the RAB7L1 expression level was higher in adenoma tissues from older PA patients, and the RAB7L1 expression level was higher in adenoma tissues from patients with smaller adenomas (size≤2cm) than those with larger adenomas (size>2cm).

An injectable double cross-linked hydrogel adhesive inspired by synergistic effects of mussel foot proteins for biomedical application.

Hydrogel adhesives with high tissue adhesion, biodegradability and biocompatibility are benefit for promoting surgical procedures and minimizing the pain and post-surgical complications of patients. In this paper, an injectable mussel inspired double cross-linked hydrogel adhesive composed of thiolated mussel inspired chitosan (CSDS) and tetra-succinimidyl carbonate polyethylene glycol (PEG-4S) was designed and developed. CSDS was synthesized with thiol and catechol groups inspired by the synergistic effect of mussel foot proteins (mfps). The double cross-linked hydrogel was first formed by the addition of sodium periodate (or Fe3+) and then double cross-linked with PEG-4S. The results showed that the mechanical and adhesion properties of the double cross-linked hydrogels were significantly improved by the synergistic effects of the functional groups. And the prepared hydrogels showed good cytocompatibility which evaluated by determining the viability of L929 cells and human umbilical vein endothelial cells (HUVECs). Additionally, the biodegradability and biocompatibility in vivo were further confirmed by subcutaneous implantation in mice model, and the histological analysis results identified that the prepared hydrogels were in vivo biocompatible. This work presents an injectable mussel inspired double cross-linked hydrogels that can use as a potential hydrogel adhesive for biomedical application.

Clinical characteristics of 276 hospitalized patients with coronavirus disease 2019 in Zengdu District, Hubei Province: a single-center descriptive study.

BACKGROUND: We aimed to report the epidemiological and clinical characteristics of hospitalized patients with coronavirus disease-19 (COVID-19) in Zengdu District, Hubei Province, China. METHODS: Clinical data on COVID-19 inpatients in Zengdu Hospital from January 27 to March 11, 2020 were collected; this is a community hospital in an area surrounding Wuhan and supported by volunteer doctors. All hospitalized patients with COVID-19 were included in this study. The epidemiological findings, clinical features, laboratory findings, radiologic manifestations, and clinical outcomes of these patients were analyzed. The patients were followed up for clinical outcomes until March 22, 2020. Severe COVID-19 cases include severe and critical cases diagnosed according to the seventh edition of China's COVID-19 diagnostic guidelines. Severe and critical COVID-19 cases were diagnosed according to the seventh edition of China's COVID-19 diagnostic guidelines. RESULTS: All hospitalized COVID-19 patients, 276 (median age: 51.0 years), were enrolled, including 262 non-severe and 14 severe patients. The proportion of patients aged over 60 years was higher in the severe group (78.6%) than in the non-severe group (18.7%, p < 0.01). Approximately a quarter of the patients (24.6%) had at least one comorbidity, such as hypertension, diabetes, or cancer, and the proportion of patients with comorbidities was higher in the severe group (85.7%) than in the non-severe group (21.4%, p < 0.01). Common symptoms included fever (82.2% [227/276]) and cough (78.0% [218/276]). 38.4% (106/276) of the patients had a fever at the time of admission. Most patients (94.9% [204/276]) were cured and discharged; 3.6% (10/276) deteriorated to a critical condition and were transferred to another hospital. The median COVID-19 treatment duration and hospital stay were 14.0 and 18.0 days, respectively. CONCLUSIONS: Most of the COVID-19 patients in Zengdu had mild disease. Older patients with underlying diseases were at a higher risk of progression to severe disease. The length of hospital-stay and antiviral treatment duration for COVID-19 were slightly longer than those in Wuhan. This work will contribute toward an understanding of COVID-19 characteristics in the areas around the core COVID-19 outbreak region and serve as a reference for decision-making for epidemic prevention and control in similar areas.

Ulinastatin reduces postoperative bleeding and red blood cell transfusion in patients undergoing cardiac surgery: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Ulinastatin is a type of glycoprotein and a nonspecific wide-spectrum protease inhibitor like antifibrinolytic agent aprotinin. Whether Ulinastatin has similar beneficial effects on blood conservation in cardiac surgical patients as aprotinin remains undetermined. Therefore, a systematic review and meta-analysis were performed to evaluate the effects of Ulinastatin on perioperative bleeding and transfusion in patients who underwent cardiac surgery. METHODS: Electronic databases were searched to identify all clinical trials comparing Ulinastatin with placebo/blank on postoperative bleeding and transfusion in patients undergoing cardiac surgery. Primary outcomes included perioperative blood loss, blood transfusion, postoperative re-exploration for bleeding. Secondary outcomes include perioperative hemoglobin level, platelet counts and functions, coagulation tests, inflammatory cytokines level, and so on. For continuous variables, treatment effects were calculated as weighted mean difference (WMD) and 95% confidential interval (CI). For dichotomous data, treatment effects were calculated as odds ratio and 95% CI. Statistical significance was defined as P < .05. RESULTS: Our search yielded 21 studies including 1310 patients, and 617 patients were allocated into Ulinastatin group and 693 into Control (placebo/blank) group. There was no significant difference in intraoperative bleeding volume, postoperative re-exploration for bleeding incidence, intraoperative red blood cell transfusion units, postoperative fresh frozen plasma transfusion volumes and platelet concentrates transfusion units between the 2 groups (all P > .05). Ulinastatin reduces postoperative bleeding (WMD = -0.73, 95% CI: -1.17 to -0.28, P = .001) and red blood cell (RBC) transfusion (WMD = -0.70, 95% CI: -1.26 to -0.14, P = .01), inhibits hyperfibrinolysis as manifested by lower level of postoperative D-dimer (WMD = -0.87, 95% CI: -1.34 to -0.39, P = .0003). CONCLUSION: This meta-analysis has found some evidence showing that Ulinastatin reduces postoperative bleeding and RBC transfusion in patients undergoing cardiac surgery. However, these findings should be interpreted rigorously. Further well-conducted trials are required to assess the blood-saving effects and mechanisms of Ulinastatin.

Functional BDNF rs7124442 Variant Regulated by miR-922 is Associated with Better Short-Term Recovery of Ischemic Stroke.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin, which contributes to the neuronal survival and synaptic plasticity. This study investigated the associations of BDNF polymorphisms at the 3'-untranslated region with risk and outcome of ischemic stroke in a Chinese Han population. METHODS: 500 patients and 520 controls were enrolled for BDNF rs7124442 genotyping. The binding of miR-922 to BDNF rs7124442 was examined by luciferase assay; BDNF expression was assessed using qRT-PCR. RESULTS: Alcohol consumption, cigarette smoking, diabetes, hypertension (all P < 0.001) and higher serum triglycerides concentration (P = 0.009) were associated with an increased risk of developing ischemic stroke. After adjusted for age and sex, logistic regression analysis showed that IS patients harbored with rs7124442 TC genotype had a milder initial stroke (Dominant model: OR = 0.45, 95% CI = 0.25-0.81, P = 0.015), and also showed a better short-term recovery (Dominant model: OR = 0.39, 95% CI =0.24-0.68, P = 0.003). Furthermore, we found that co-transfection of hsa-miR-922 mimics with BDNF 3'-UTR containing the mutated allele C changed luciferase activity when compared to co-transfection with BDNF 3'-UTR containing the wild-type allele. Besides, patients carrying BDNF rs712444 TC or CC genotype had an increased level of BDNF compared with patients with the TT genotype. CONCLUSION: Our study demonstrates that the SNP rs7124442 in BDNF 3'-UTR, through affecting the regulatory role of miR-922 in BDNF expression, might act as a protective factor for the outcome of patients with ischemic stroke.

Nanofibrous vascular scaffold prepared from miscible polymer blend with heparin/stromal cell-derived factor-1 alpha for enhancing anticoagulation and endothelialization.

There is an urgent clinical demand to develop a functional small diameter vascular graft with long-term patency, which mainly relies on the anticoagulation and endothelialization of the vascular graft. In addition, improved degradation of vascular graft provides more space for cell infiltration and facilitates remodeling of blood vessel. In this study, an elastic and biomimetic nanofibrous vascular scaffold with improved degradability was prepared by adding poly(lactic-co-glycolic acid) (PLGA) into the poly(L-lactic acid) (PLLA)/poly(L-lactide-co-ε-caprolactone) (PLCL) blend using thermally induced phase separation (TIPS) technique. The incorporation of PLGA also improved the hydrophilicity of the composite scaffold. Then the vascular scaffold was surface modified by combination of heparin and stromal cell-derived factor-1 alpha (SDF-1α). The results of whole blood clotting kinetics and plasma recalcification profiles indicated that heparinized modification significantly enhanced the anticoagulation of vascular scaffold. In vitro cell culture assays demonstrated the immobilized SDF-1α facilitated recruitment of endothelial progenitor cells (EPCs), migration and proliferation of mature endothelial cells, human umbilical vein endothelial cells (HUVECs), and expression of VE-cadherin/CD144 and endothelial nitric oxide synthase (eNOS) genes in HUVECs, thereby accelerating the endothelialization of the modified vascular scaffold. Besides, the nanofibrous vascular scaffold modified with heparin and SDF-1α inhibited the proliferation of human vascular smooth muscle cells (HVSMCs). Therefore, the phase separated nanofibrous vascular scaffold modified with heparin and SDF-1α shows the promising in vitro performance as a functional small diameter vascular graft.

Enhanced biocompatibility of poly(l­lactide­co­epsilon­caprolactone) electrospun vascular grafts via self-assembly modification.

Thousands of coronary artery bypass surgeries are performed in the world every year. But there is still no alternative to autologous vessel transplantation yet. In the present study, we optimized the weight ratio of chitosan/poly(l­lactide­co­epsilon­caprolactone) (CS/PLCL) of the electrospun scaffolds, which lead to suitable mechanical properties, such as tensile strength, ultimate strain, elastic modulus and burst pressure. Besides, the scaffolds possessed the structure that mimics the native extracellular matrix. To improve the anticoagulant property of vascular grafts and avoid the use of toxic reagents, dextran sulfate was used to modify the scaffold by self-assembly method. The result of attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) demonstrated the successful modification of dextran sulfate on the scaffold. Simultaneously, modification with dextran sulfate enhanced the hydrophilicity of the scaffold. Then the degradation property of the scaffolds was evaluated by the pH value of the phosphate buffer solution (PBS) soaking solutions and mass loss of the scaffolds. Hemocompatibility test was then performed to determine the enhanced anticoagulation and antihemolysis properties of the modified scaffold. The in vitro cell viability results showed that the modified scaffold possessed favorable cell viability to the human vascular cells. Furthermore, the scaffolds were subcutaneously implanted in mice for 4 weeks. Compared to the unmodified and pure PLCL tubular scaffolds, the histological analysis indicated that the modified tubular scaffolds possessed low inflammatory response and more infiltrated cells in the scaffold. Therefore, our studies showed that dextran sulfate modified scaffold might pave the way to fabricate small-diameter vascular grafts for clinical application.

Bilayered Scaffold Prepared from a Kartogenin-Loaded Hydrogel and BMP-2-Derived Peptide-Loaded Porous Nanofibrous Scaffold for Osteochondral Defect Repair.

Recently, a bilayered scaffold with an anisotropic structure mimicking a native osteochondral tissue shows considerable potential for treating osteochondral defects. Herein, a bilayered scaffold consisting of biomimetic cartilage and a subchondral bone architecture was constructed for repairing osteochondral defect. A hydrogel prepared by the Schiff base reaction of gelatin, silk fibroin, and oxidized dextran was designed as the cartilage layer, while a nanofibrous scaffold with a macroporous structure prepared from the polymer blend of poly(l-lactic acid)/poly(lactic-co-glycolic acid)/poly(ε-caprolactone) using the dual phase separation technique served as a subchondral layer. The subchondral layer was then treated with polydopamine coating for osteogenic factor immobilization. To facilitate the chondrogenic and osteogenic differentiation of bone marrow mesenchymal stem cells on the bilayered scaffold, the cartilage-inducing drug kartogenin (KGN) and osteogenic-inducing factor bone morphogenetic protein 2-derived peptides (P24 peptides) were, respectively, loaded on the subchondral layer. Next, the in vitro release of KGN and P24 peptide from the corresponding layer was monitored, respectively, and the results showed that both the release time of KGN and P24 peptides would last for more than 28 days. The in vitro results indicated that the KGN-loaded cartilage layer and P24 peptides-loaded subchondral layer were capable of supporting cell proliferation, and induced the chondrogenic and osteogenic differentiation, respectively. Furthermore, the in vivo experiments suggested that the bilayered scaffold significantly accelerated the regeneration of the osteochondral tissue in the rabbit knee joint model. Consequently, this bilayered scaffold loaded with KGN and P24 peptides would be a promising candidate for repairing osteochondral defect.

Three-dimensional electrospun nanofibrous scaffolds displaying bone morphogenetic protein-2-derived peptides for the promotion of osteogenic differentiation of stem cells and bone regeneration.

Tissue scaffolds with three-dimensional (3D) nanofibrous biomimetic structures have attracted attention in the field of bone regeneration. In recent years, emerging strategies based on electrospinning technologies have facilitated the preparation of 3D nanofibrous scaffolds. Based on these developments, in this study, 3D scaffolds possessing both nanofibrous morphologies and interconnected pores were fabricated for their potential in bone tissue engineering. By combining homogenizing, freeze-drying, and thermal crosslinking techniques, nano-hydroxyapatite/PLLA/gelatin (nHA/PLA/GEL) 3D nanofibrous scaffolds were prepared using pre-fabricated electrospun nanofibers. Then, utilizing a polydopamine (pDA)-assisted coating strategy, bone morphogenetic protein-2 (BMP-2)-derived peptides were further immobilized onto the 3D scaffolds to obtain the resulting nano-hydroxyapatite/PLLA/gelatin-peptide (nHA/PLA/GEL-PEP) 3D nanofibrous scaffolds capable of sustained release. Bone mesenchymal stem cells (BMSCs) were cultured on the 3D nanofibrous scaffolds, then relative cell viability, alkaline phosphatase (ALP) activity, and gene expression assays were performed to study the effects of the scaffolds on cell growth and osteogenic differentiation in vitro. Furthermore, the ability of bone formation in vivo was evaluated using a rat cranial bone defect model. In vitro and in vivo results demonstrated that the 3D nanofibrous scaffolds incorporated with nHA and BMP-2 peptides exhibited favorable biocompatibility and osteoinductivity. Therefore, these nanofibrous scaffolds have excellent potential in bone regenerative medicine.

NOX4 rs11018628 polymorphism associates with a decreased risk and better short-term recovery of ischemic stroke.

Single-nucleotide polymorphisms (SNPs) play an important role in our susceptibility to disease, the severity of illness and the way our body responds to treatment. This study evaluated the impact of three polymorphisms on the susceptibility and functional outcome of ischemic stroke (IS). Three hundred and eight patients and 300 healthy volunteers were enrolled. Polymorphisms of NOX4 rs11018628, MTHFR rs1801133 and NEIL3 rs12645561 were detected in both groups. Smoking (P<0.001), drinking (P<0.001), hypertension (P<0.001) and diabetes (P=0.006), as traditional vascular risk factors for IS, were confirmed in our study. Logistic regression analyses with adjustment for age, sex, smoking, drinking, diabetes, hypertension and total cholesterol showed that the variant genotypes of NOX4 rs11018628 were associated with a significantly decreased risk (Dominant model: OR=0.32, 95% CI=0.22-0.48, P<0.001) and a better short-term recovery of IS (Dominant model: OR=0.57, 95% CI=0.35-0.95, P=0.029). This study demonstrates that the NOX4 rs11018628 SNP is associated with decreased risk in developing IS and better short-term recovery of patients. This suggests that the genetic variant of NOX4 rs11018628 may contribute to the etiology of IS.

Macroporous nanofibrous vascular scaffold with improved biodegradability and smooth muscle cells infiltration prepared by dual phase separation technique.

INTRODUCTION: The fast degradation of vascular graft and the infiltration of smooth muscle cells (SMCs) into the vascular graft are considered to be critical for the regeneration of functional neo-vessels. In our previous study, a novel dual phase separation technique was developed to one-pot prepare macroporous nanofibrous poly(L-lactic acid) (PLLA)/poly(ε-caprolactone) (PCL) vascular scaffold by phase separating the immiscible polymer blend. However, the slow degradation of PLLA/PCL limited cell infiltration. Herein, we hypothesized that poly(lactic-co-glycolic acid) (PLGA) would be miscible with PLLA but immiscible with PCL. Then, PLGA can be introduced into the PLLA/PCL blend to fabricate macroporous nanofibrous scaffold with improved biodegradability by using dual phase separation technique. MATERIALS AND METHODS: The miscibility of PLGA with PLLA and PCL was evaluated. Then, the PLLA/PLGA/PCL scaffold was prepared by dual phase separation technique. The prepared scaffolds were characterized in terms of the morphology, in vitro degradation, mechanical properties, and cells' infiltration and viability for human vascular SMCs (HVSMCs). Finally, platelet-derived growth factor-BB (PDGF-BB) was immobilized on the scaffold and its effect on the bioactivity of HVSMCs was studied. RESULTS: PLGA is miscible with PLLA but immiscible with PCL as hypothesized. The addition of PLGA enlarged the pore size and improved the biodegradability of composite scaffold. Notably, PLLA/PLGA/PCL scaffold with the blend ratio of 30:40:30 possessed improved pore interconnectivity for cells' infiltration and enough mechanical properties. Moreover, HVSMCs could grow and infiltrate into this scaffold, and surface modification with PDGF-BB on the nanofibrous scaffold enhanced HVSMCs migration and proliferation. CONCLUSION: This study provides a strategy to expand dual phase separation technique into utilizing ternary even multinary polymer blend to fabricate macroporous nanofibrous scaffold with improved physicochemical properties. The prepared PLLA/PLGA/PCL scaffold would be promising for the regeneration of functional tunica media in vascular tissue engineering.

Self-Assembled Hydroxyapatite-Graphene Scaffold for Photothermal Cancer Therapy and Bone Regeneration.

Repairing large tumor-related bone defects remains a difficult clinical problem because of the significant risk of locoregional relapse after surgical curettage. In this study, a composite scaffold of nano-hydroxyapatite (nHA) and reduced graphene oxide (rGO) sheets was fabricated by self-assembly, and a 20 wt% nHA-rGO sheet solution formed the most stable hydrogel. In vitro, nHA-rGO scaffolds killed all but 8% of osteosarcoma cells (MG-63) under 808 nm near-infrared laser irradiation for 20 min. SEM images and live/dead staining of MG-63 cells in nHA-rGO also confirmed the therapeutic efficacy of the scaffolds. Tumors implanted with nHA-rGO scaffolds reached 60 °C after 4 min. of irradiation; xenografted tumors stopped growth or even decreased in size after photothermal therapy. In vitro the scaffolds promoted adhesion, proliferation, and osteogenic mineralization of rat bone marrow stem cells (rBMSCs). Live cell staining and CCK-8 showed good proliferation for rBMSCs in nHA-rGO scaffolds. Alkaline phosphatase activity and qPCR demonstrated osteogenic mineralization of rBMSCs in nHA-rGO scaffolds. Micro-CT and histology verified that the scaffold promotes bone regeneration in rat cranial defects. At 8 weeks, 35% of the cranial defect area remained in the scaffold-implanted group, while 80% remained for the control. Bone mineral density of the scaffold-implanted group reached 284.58±20.78 mg/cm³, indicating new bone mineral deposition, versus only 96.04±2.67 mg/cm³ for the control. Histology showed scaffold stimulation of osteoblast mineralization and collagen deposition. Therefore, nHA-rGO scaffolds may be an effective treatment of large tumor-related bone defects due to their excellent photothermal and osteogenic effects.