Preliminary study of improving immune tolerance in vivo of bioprosthetic heart valves through a novel antigenic removal method.

The durability of bioprosthetic heart valves is always compromised by the inherent antigenicity of biomaterials. Decellularization has been a promising approach to reducing the immunogenicity of biological valves. However, current methods are insufficient in eliminating all immunogenicity from the biomaterials, necessitating the exploration of novel techniques. In this study, we investigated using a novel detergent, fatty alcohol polyoxyethylene ether sodium sulfate (AES), to remove antigens from bovine pericardium. Our results demonstrated that AES treatment achieved a higher pericardial antigen removal rate than traditional detergent treatments while preserving the mechanical properties and biocompatibility of the biomaterials. Moreover, we observed excellent immune tolerance in the in vivo rat model. Overall, our findings suggest that AES treatment is a promising method for preparing biological valves with ideal clinical application prospects.

A NEW DOSE DETERMINATION METHOD FOR HP(3) AND DP LENS FOR BETA REFERENCE RADIATION QUALITIES.

For the purpose of obtaining the smaller uncertainties for Hp(3) and Dp lens in 90Sr/90Y beta reference fields, a new dose determination method based on the Monte-Carlo simulation was proposed. The conversion coefficients from the absorbed dose in air, at the reference point of the extrapolation ionisation chamber, Dair, det to Hp(3; α) and the conversion factors from Dair, det to Dp lens(α) were calculated with EGSnrc, respectively, for the irradiation angles from 0° to 60°. Compared with the dose determination method in International Organization for Standardization (ISO) 6980 standard, the uncertainty reductions of 7.7-52.8% for Hp(3; α) and 7.9-55.0% for Dp lens(α) were achieved, respectively. In addition, for the conversion coefficients from the reference absorbed dose DR to Hp(3; α), the calculations were performed for more irradiation conditions, which are not included in the current ISO 6980 standard. For the calculations of the conversion factors from DR to Dp lens(α), the eye and head phantoms with Chinese characteristics were utilised, which makes the conversion factors more suitable for use in China.

The hybrid crosslinking method improved the stability and anti-calcification properties of the bioprosthetic heart valves.

The bioprosthetic heart valves (BHVs) are the best option for the treatment of valvular heart disease. Glutaraldehyde (Glut) is commonly used as the golden standard reagent for the crosslinking of BHVs. However, the obvious defects of Glut, including residual aldehyde toxicity, degradation and calcification, increase the probability of valve failure in vivo and motivated the exploration of alternatives. Thus, the aim of this study is to develop a non-glutaraldehyde hybrid cross-linking method composed of Neomycin Trisulfate, Polyethylene glycol diglycidyl ether and Tannic acid as a substitute for Glut, which was proven to reduce calcification, degradation, inflammation of the biomaterial. Evaluations of the crosslinked bovine pericardial included histological and ultrastructural characterization, biomechanical performance, biocompatibility and structural stability test, and in vivo anti-inflammation and anti-calcification assay by subcutaneous implantation in juvenile Sprague Dawley rats. The results revealed that the hybrid crosslinked bovine pericardial were superior to Glut crosslinked biomaterial in terms of better hydrophilicity, thermodynamics stability, hemocompatibility and cytocompatibility, higher Young's Modulus, better stability and resistance to enzymatic hydrolysis, and lower inflammation, degradation and calcification levels in subcutaneous implants. Considering all above performances, it indicates that the hybrid cross-linking method is appropriate to replace Glut as the method for BHV preparation, and particularly this hybrid crosslinked biomaterials may be a promising candidate for next-generation BHVs.

Effective dispersion of oxidized multi-walled carbon nanotubes using a water-soluble N,O-carboxymethyl chitosan via non-covalent interaction.

Dispersible multi-walled carbon nanotubes (MWCNTs) in water have been widely applied in the nanotechnology field. This study reports a water-soluble N,O-carboxymethyl chitosan(N,O-CMCS) assisted individual dispersion of oxidized multi-walled carbon nanotubes (oMWCNTs) as a dispersant. First, the dispersing agent N,O-CMCS was successfully synthesized using the nucleophilic substitution of deacetylated chitosan with chloroacetic acid in an alkaline solution. It was further confirmed using Fourier transform infrared spectroscopy (FTIR). Second, after the treatment with the concentrated hydrochloric acid, the prepared oMWCNTs were dispersed in an aqueous solution of N,O-CMCS under ultrasonic vibrations. Finally, the dispersed aqueous solution was subjected to centrifugation to collect the supernatant of individually dispersed N,O-CMCS/oMWCNTs. In addition, transmission electron microscopy (TEM) further confirmed that the purity of oMWCNTs was improved after the acidification progress. Besides, the stability of the dispersion solution was evidenced by digital photos of oMWCNTs dispersed by N,O-CMCS before and after. Moreover, the UV-vis spectrum (the characteristic peak of dispersed oMWCNTs downshifted 13 nm) showed that the supernatant was enriched by the individual oMWCNTs. In particular, the analytical results of FTIR (the -NH2 band of N,O-CMCS downshifted 7 cm-1), resonance Raman spectroscopy (the I D/I G ratio of dispersed oMWCNTs only increased 0.14), and XRD identified the formation of a non-convalent interaction between N,O-CMCS and oMWCNTs. These findings reveal the dispersing nature of N,O-CMCS towards oMWCNTs in water media.

A Novel Crosslinking Method for Improving the Anti-Calcification Ability and Extracellular Matrix Stability in Transcatheter Heart Valves.

More than 200,000 patients with aortic diseases worldwide undergo surgical valve replacement each year, and transcatheter heart valves (THV) have been more widely used than ever before. However, THV made by the glutaraldehyde (Glut) crosslinking method has the disadvantage of being prone to calcification, which significantly reduces the durability of biomaterials. In this study, we applied a novel crosslinking method using ribose in THV for the first time, which can decrease calcification and increase the stability of the extracellular matrix (ECM). We incubated the bovine pericardium (BP) in ribose solution at 37°C by shaking for 12 days and confirmed that the structure of the BP was more compact than that of the Glut group. Moreover, the ribose method remarkably enhanced the biomechanical properties and provided reliable resistance to enzymatic degradation and satisfactory cellular compatibility in THV. When the BP was implanted subcutaneously in vivo, we demonstrated that ECM components were preserved more completely, especially in elastin, and the immune-inflammatory response was more moderate than that in the Glut treatment group. Finally, the ribose-cross-linked materials showed better anti-calcification potential and improved durability of THV than Glut-cross-linked materials.

Improved Cytocompatibility and Reduced Calcification of Glutaraldehyde-Crosslinked Bovine Pericardium by Modification With Glutathione.

Bioprosthetic heart valves (BHVs) used in clinics are fabricated via glutaraldehyde (GLUT) crosslinking, which results in cytotoxicity and causes eventual valve calcification after implantation into the human body; therefore, the average lifetime and application of BHVs are limited. To address these issues, the most commonly used method is modification with amino acids, such as glycine (GLY), which is proven to effectively reduce toxicity and calcification. In this study, we used the l-glutathione (GSH) in a new modification treatment based on GLUT-crosslinked bovine pericardium (BP) as the GLUT + GSH group, BPs crosslinked with GLUT as GLUT-BP (control group), and GLY modification based on GLUT-BP as the GLUT + GLY group. We evaluated the characteristics of BPs in different treatment groups in terms of biomechanical properties, cell compatibility, aldehyde group content detection, and the calcification content. Aldehyde group detection tests showed that the GSH can completely neutralize the residual aldehyde group of GLUT-BP. Compared with that of GLUT-BP, the endothelial cell proliferation rate of the GLUT + GSH group increased, while its hemolysis rate and the inflammatory response after implantation into the SD rat were reduced. The results show that GSH can effectively improve the cytocompatibility of the GLUT-BP tissue. In addition, the results of the uniaxial tensile test, thermal shrinkage temperature, histological and SEM evaluation, and enzyme digestion experiments proved that GSH did not affect the ECM stability and biomechanics of the GLUT-BP. The calcification level of GLUT-BP modified using GSH technology decreased by 80%, indicating that GSH can improve the anti-calcification performance of GLUT-BP. Compared with GLUT-GLY, GLUT + GSH yielded a higher cell proliferation rate and lower inflammatory response and calcification level. GSH can be used as a new type of anti-calcification agent in GLUT crosslinking biomaterials and is expected to expand the application domain for BHVs in the future.

Photooxidation and Pentagalloyl Glucose Cross-Linking Improves the Performance of Decellularized Small-Diameter Vascular Xenograft In Vivo.

Small-diameter vascular grafts have a significant need in peripheral vascular surgery and procedures of coronary artery bypass graft (CABG); however, autografts are not always available, synthetic grafts perform poorly, and allografts and xenografts dilate, calcify, and induce inflammation after implantation. We hypothesized that cross-linking of decellularized xenogeneic vascular grafts would improve the mechanical properties and biocompatibility and reduce inflammation, degradation, and calcification in vivo. To test this hypothesis, the bovine internal mammary artery (BIMA) was decellularized by detergents and ribozymes with sonication and perfusion. Photooxidation and pentagalloyl glucose (PGG) were used to cross-link the collagen and elastin fibers of decellularized xenografts. Modified grafts' characteristics and biocompatibility were studied in vitro and in vivo; the grafts were implanted as transposition grafts in the subcutaneous of rats and the abdominal aorta of rabbits. The decellularized grafts were cross-linked by photooxidation and PGG, which improved the grafts' biomechanical properties and biocompatibility, prevented elastic fibers from early degradation, and reduced inflammation and calcification in vivo. Short-term aortic implants in the rabbits showed collagen regeneration and differentiation of host smooth muscle cells. No occlusion and stenosis occurred due to remodeling and stabilization of the neointima. A good patency rate (100%) was maintained. Notably, implantation of non-treated grafts exhibited marked thrombosis, an inflammatory response, calcification, and elastin degeneration. Thus, photooxidation and PGG cross-linking are potential tools for improving grafts' biological performance within decellularized small-diameter vascular xenografts.

Water-soluble carboxymethyl chitosan (WSCC)-modified single-walled carbon nanotubes (SWCNTs) provide efficient adsorption of Pb(ii) from water.

Nanocomposites play a key role in the removal of toxic metal(loid)s from environmental water. In this study, we investigated the adsorption capability of water-soluble carboxymethyl chitosan (WSCC)-modified functionally oxidized single walled carbon nanotubes (oSWCNTs) for rapid and efficient removal of toxic Pb(ii) from water. The WSCC-oSWCNTs nanocomposite was prepared by an acid treatment of SWCNTs followed by an ultrasonic dispersion process using WSCC as dispersant. The morphology and chemical characteristics of the WSCC-oSWCNTs nanocomposite were further identified using various characterization techniques (i.e., transmission electron microscopy, TEM; scanning electron microscopy, SEM; Raman spectra; Fourier transform infrared spectroscopy, FTIR; X-ray photoelectron spectroscopy, XPS; nitrogen adsorption-desorption isotherm test). The efficiency of the adsorption process in batch experiments was investigated via determining various factor effects (i.e. WSCC-oSWCNTs nanocomposite concentration, solution pH, initial Pb(ii) concentration, contact time, and reaction temperature). Kinetic results showed that the adsorption process followed a pseudo-second-order, while an isotherm results study showed that the adsorption process followed the Langmuir and Freundlich isotherm models at the same time. In addition, the van't Hoff equation was used to calculate thermodynamic parameters for assessing the endothermic properties and spontaneity of the adsorption process. The WSCC-oSWCNTs nanocomposite manifested a high adsorption capacity for Pb(ii) (113.63 mg g-1) via electrostatic interactions and ion-exchange, as its adsorption rate could reach up to 98.72%. This study, therefore, provides a novel adsorbent for the removal and detection of harmful residues (i.e. toxic metal(loid)s) from environmental water, such as industry wastewater treatment and chemical waste management.

Vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized small-diameter vascular grafts by modulating the local inflammatory response.

Small-diameter vascular grafts (diameter <6 mm) are in high demand in clinical practice. Neointimal hyperplasia, a common complication after implantation of small-diameter vascular grafts, is one of the common causes of graft failure. Modulation of local inflammatory responses is a promising strategy to attenuates neointimal hyperplasia. Vascular endothelial growth factor (VEGF) is an angiogenesis stimulator that also induces macrophage polarization and modulates inflammatory responses. In the present study, we evaluated the effect of VEGF on the neointima hyperplasia and local inflammatory responses of decellularized vascular grafts. In the presence of rhVEGF-165 in RAW264.6 macrophage culture, rhVEGF-165 induces RAW264.6 macrophage polarization to M2 phenotype. Decellularized bovine internal mammary arteries were implanted into the subcutaneous and infrarenal abdominal aorta of New Zealand rabbits, with rhVEGF-165 applied locally to the adventitial of the grafts. The vascular grafts were removed en-bloc and submitted to histological and immunofluorescence analyses on days 7 and 28 following implantation. The thickness of the fibrous capsule and neointima was thinner in the VEGF group than that in the control group. In the immunofluorescence analysis, the number of M2 macrophages and the ratio of M2/M1 macrophages in vascular grafts in the VEGF group were higher than those in the control group, and the proinflammatory factor IL-1 was expressed less than in the control group, but the anti-inflammatory factor IL-10 was expressed more. In conclusion, local VEGF administration attenuates neointimal hyperplasia in decellularized small-diameter vascular grafts by inducing macrophage M2 polarization and modulating the inflammatory response.

CALCULATION OF THE DOSE CONVERSION COEFFICIENTS FOR CHINESE EYE LENS UNDER PHOTON EXPOSURE.

In this work, the conversion coefficients from air kerma to the eye lens dose were calculated for photon exposures using the detailed eye and head Monte-Carlo (MC) model with the Chinese adult parameters. To verify the MC model and the simulation method, the conversion coefficients from fluence to the eye lens dose for mono-energy electrons (0.7-12 MeV) were calculated and compared with other studies. Then the conversion coefficients from air kerma to the doses in the entire lens and in the sensitive volume were calculated, respectively, for mono-energy photons (0.01-50 MeV) at different incidence angles (0-90°, in step of 15°). A small difference was found between the calculated conversion coefficient and the ICRP recommended value. The difference could be mainly due to the difference in their geometry characteristic of the eye and head models. In addition, the uncertainty analysis of the calculated conversion coefficients was performed in detail. The calculated dose conversion coefficient of the eye lens can be used to evaluate the eye lens dose for Chinese occupational staffs in external photon fields. And it can be used to determine the personal absorbed dose in the eye lens Dp lens in photon reference radiation fields.

Yak Pericardium as an Alternative Biomaterial for Transcatheter Heart Valves.

Transcatheter aortic valve implantation (TAVI) has received much attention and development in the past decade due to its lower risk of complication and infections compared to a traditional open thoracotomy. However, the current commercial transcatheter heart valve does not fully meet clinical needs; therefore, new biological materials must be found in order to meet these requirements. We have discovered a new type of biological material, the yak pericardium. This current research studied its extracellular matrix structure, composition, mechanical properties, and amino acid content. Folding experiment was carried out to analyze the structure and mechanics after folding. We also conducted a subcutaneous embedding experiment to analyze the inflammatory response and calcification after implantation. Australian bovine pericardium, local bovine pericardium, and porcine pericardium were used as controls. The overall structure of the yak pericardium is flat, the collagen runs regularly, it has superior mechanical properties, and the average thickness is significantly lower than that of the Australian bovine and the local bovine pericardium control groups. The yak pericardium has a higher content of elastic fibers, showing that it has a better compression resistance effect during the folding experiment as well as having less expression of transplantation-related antigens. We conducted in vivo experiments and found that the yak pericardium has less inflammation and a lower degree of calcification. In summary, the yak pericardium, which is thin and strong, has lower immunogenicity and outstanding anti-calcification effects may be an excellent candidate valve leaflet material for TAVI.

Impacts of Immunometabolism on Male Reproduction.

The physiological process of male reproduction relies on the orchestration of neuroendocrine, immune, and energy metabolism. Spermatogenesis is controlled by the hypothalamic-pituitary-testicular (HPT) axis, which modulates the production of gonadal steroid hormones in the testes. The immune cells and cytokines in testes provide a protective microenvironment for the development and maturation of germ cells. The metabolic cellular responses and processes in testes provide energy production and biosynthetic precursors to regulate germ cell development and control testicular immunity and inflammation. The metabolism of immune cells is crucial for both inflammatory and anti-inflammatory responses, which supposes to affect the spermatogenesis in testes. In this review, the role of immunometabolism in male reproduction will be highlighted. Obesity, metabolic dysfunction, such as type 2 diabetes mellitus, are well documented to impact male fertility; thus, their impacts on the immune cells distributed in testes will also be discussed. Finally, the potential significance of the medicine targeting the specific metabolic intermediates or immune metabolism checkpoints to improve male reproduction will also be reassessed.

Promoter hypermethylation of cysteine dioxygenase type 1 in patients with non-small cell lung cancer.

In the present study, promoter hypermethylation of cysteine dioxygenase type 1 (CDO1) was evaluated in non-small cell lung cancer (NSCLC) tissues to assess the value of CDO1 as a novel biomarker to improve the diagnosis of NSCLC. Tumor tissue samples and corresponding normal lung tissue samples from 42 patients with NSCLC were obtained at the Department of Thoracic Surgery, The Second Xiangya Hospital (Changsha, China). Conventional methylation-specific PCR (cMSP) and methylation-on-beads followed by quantitative methylation-specific PCR (MOB-qMSP) were used to analyze the tumor and normal lung tissue samples. Using these two methods, promoter DNA hypermethylation of the CDO1 gene was detected in 59.4 and 71.0% of tumor tissues of patients with NSCLC and in 9.4 and 0% of normal lung tissue, respectively. Compared with the rate of methylation in the well-differentiated NSCLC tissues (15.4 and 55.6%, respectively), the rate of CDO1 gene promoter methylation was higher in the poorly differentiated tissues (89.5 and 92.3%, respectively). Overall, it was demonstrated that the MOB-qMSP method had a higher positive detection rate for CDO1 hypermethylation compared with the cMSP method. In conclusion, CDO1 gene promoter hypermethylation was more frequently observed in NSCLC tissues compared with in normal lung tissues, and a high methylation frequency of the CDO1 gene in biopsy specimens of NSCLC was associated with the degree of differentiation.

Effect of miR-26a-5p targeting ADAM17 gene on apoptosis, inflammatory factors and oxidative stress response of myocardial cells in hypoxic model.

The aim of this study was to explore the effect of miR-26a-5p targeting and regulating ADAM17 gene on myocardial cells in hypoxic model. Myocardial cells from 1 day old Sprague-Dawley rats were isolated and cultured for 3 days, and were used for experiment. The hypoxia model of myocardial cells was established after cell grouping transfection. The targeting relationship between miR-26a-5p and ADAM17 was verified by bioinformatics website prediction and double luciferase report experiment. The double luciferase report experiment showed that miR-26a-5p had a targeted relationship with ADAM17, and miR-26a-5p could target and bind ADAM17, down-regulate its expression, and the transfection efficiency of each group was good (P < 0.05). After overexpression of miR-26a-5p, cell activity was increased (P < 0.05), apoptosis was decreased (P < 0.05), and the expression levels of TNF-α, IL-1ß and IL-6 were significantly decreased (all P < 0.05). The release of creatine kinase-MB and the expression level of malondialdehyde were significantly decreased (both P < 0.05), and the expression level of superoxide dismutase was significantly increased (all P < 0.05). After overexpression of ADAM17, the results were reversed (all P < 0.05). MiR-26a-5p could target and regulate ADAM17, reduce the apoptosis of myocardial cells and the expression of inflammatory factors in acute myocardial infarction, and reduce the occurrence of oxidative stress.

Chaotic region of elastically restrained single-walled carbon nanotube.

The occurrence of chaos in the transverse oscillation of the carbon nanotube in all of the precise micro-nano mechanical systems has a strong impact on the stability and the precision of the micro-nano systems, the conditions of which are related with the boundary restraints of the carbon nanotube. To generalize some transverse oscillation problems of the carbon nanotube studied in current references, the elastic restraints at both ends of the single-walled carbon nanotube are considered by means of rotational and translational springs to investigate the effects of the boundary restraints on the chaotic properties of the carbon nanotube in this paper. Based on the generalized multi-symplectic theory, both the generalized multi-symplectic formulations for the governing equation describing the transverse oscillation of the single-walled carbon nanotube subjected to the transverse load and the constraint equations resulting from the elastic restraints are presented firstly. Then, the structure-preserving scheme with discrete constraint equations is constructed to simulate the transverse oscillation process of the carbon nanotube. Finally, the chaotic region of the carbon nanotube is captured, and the oscillations of the two extreme cases (including simply supported and cantilever) are investigated in the numerical investigations. From the numerical results, it can be concluded that the relative bending stiffness coefficient and the absolute bending stiffness coefficients at both ends of the carbon nanotube are two important factors that affect the chaotic region of the carbon nanotube, which provides guidance on the design and manufacture of precise micro-nano mechanical systems. In addition, the different routes to the chaos of the carbon nanotube in two extreme cases are revealed.