Analysis of volatile organic compounds from deep airway in the lung through intubation sampling.

Exhaled volatile organic compounds (VOCs) have been widely applied for the study of disease biomarkers. Oral exhalation and nasal exhalation are two of the most common sampling methods. However, VOCs released from food residues and bacteria in the mouth or upper respiratory tract were also sampled and usually mistaken as that produced from body metabolism. In this study, exhalation from deep airway was first directly collected through intubation sampling and analyzed. The exhalation samples of 35 subjects were collected through a catheter, which was inserted into the trachea or bronchus through the mouth and upper respiratory tract. Then, the VOCs in these samples were detected by proton transfer reaction mass spectrometry (PTR-MS). In addition, fast gas chromatography proton transfer reaction mass spectrometry (FGC-PTR-MS) was used to further determine the VOCs with the same mass-to-charge ratios. The results showed that there was methanol, acetonitrile, ethanol, methyl mercaptan, acetone, isoprene, and phenol in the deep airway. Compared with that in oral exhalation, ethanol, methyl mercaptan, and phenol had lower concentrations. In detail, the median concentrations of ethanol, methyl mercaptan, and phenol were 7.3, 0.6, and 23.9 ppbv, while those in the oral exhalation were 80.0, 5.1, and 71.3 ppbv, respectively, which meant the three VOCs mainly originated from the food residues and bacteria in the mouth or upper respiratory tract, rather than body metabolism. The research results in our study can provide references for expiratory VOC research based on oral and nasal exhalation samplings, which are more feasible in clinical practice.

A photo-degradable injectable self-healing hydrogel based on star poly(ethylene glycol)-b-polypeptide as a potential pharmaceuticals delivery carrier.

As one of the most promising biomaterials, injectable self-healing hydrogels have found broad applications in a number of fields such as local drug delivery. However, controlled release of drugs in hydrogels is still difficult to realize up to now. Here, we report a novel photo-degradable injectable self-healing hydrogel based on the hydrophobic interaction of a biocompatible four-arms star polymer, poly(ethylene glycol)-b-poly(γ-o-nitrobenzyl-l-glutamate). The hydrophobic interaction between poly(γ-o-nitrobenzyl-l-glutamate) not only connects poly(ethylene glycol)-b-poly(γ-o-nitrobenzyl-l-glutamate) together with a crosslink but also provides a hydrophobic domain to encapsulate hydrophobic pharmaceuticals such as doxorubicin (DOX). Due to the dynamic character of the hydrophobic interaction, the hydrogel exhibits excellent injectable and self-healing ability. In particular, the photolabile o-nitribenzyl ester group is cleaved under UV irradiation. As a result, the hydrophobic domain transforms into the hydrophilic one and the embedded DOX is released effectively. An increasing release ratio of DOX dramatically enhances the apoptosis ratio of HeLa cells. We expect these attractive properties may be beneficial to practical applications of the hydrogel as an effective local drug delivery means in a truly physiological environment.

Effects of combined human parathyroid hormone (1-34) and menaquinone-4 treatment on the interface of hydroxyapatite-coated titanium implants in the femur of osteoporotic rats.

The objective of this study was to investigate the effects of human parathyroid hormone (1-34) (PTH1-34; PTH) plus menaquinone-4 (vitamin K2; MK) on the osseous integration of hydroxyapatite (HA)-coated implants in osteoporotic rats. Ovariectomized female Sprague-Dawley rats were used for the study. Twelve weeks after bilateral ovariectomy, HA-coated titanium implants were inserted bilaterally in the femoral medullary canal of the remaining 40 ovariectomized rats. All animals were then randomly assigned to four groups: Control, MK, PTH and PTH + MK. The rats from groups MK, PTH and PTH + MK received vitamin K2 (30 mg/kg/day), PTH1-34 (60 µg/kg, three times a week), or both for 12 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA and the bilateral femurs of rats were harvested for evaluation. The combination of PTH and MK clearly increased the serum levels of Gla-OC (a specific marker for bone formation) compared to PTH or MK alone. The results of our study indicated that all treated groups had increased new bone formation around the surface of implants and increased push-out force compared to Control. In addition, PTH + MK treatment showed the strongest effects in histological, micro-computed tomography and biomechanical tests. In summary, our results confirm that treatment with PTH1-34 and MK together may have a therapeutic advantage over PTH or MK monotherapy on bone healing around HA-coated implants in osteoporotic rats.

Polyhistidine-Based Metal Coordination Hydrogels with Physiologically Relevant pH Responsiveness and Enhanced Stability through a Novel Synthesis.

Utilizing the abnormal physiological conditions of disease tissues can result in a site-specific functionality with high control and efficiency of stimuli-responsive hydrogels. Here, a physiologically relevant pH-responsive and self-healing hydrogel is reported based on coordination between Ni2+ and four-arm poly(ethylene glycol)-b-polyhistidine (4PEG-PHis) that is synthesized by a novel and facile PHis preparation method using amino-terminalized four-arm PEG as the macroinitiator. Reversible PHisNi coordination bonds endow the hydrogel with multistimuli-triggered sol-gel transition (physiologically relevant pH, EDTA) and self-healing properties. It is also demonstrated that 4PEG-PHis could be used as an injectable hydrogel in phosphate buffer (pH 7.4), and excellent stability in neutral buffer via multivalent coordination is shown, thus indicating its potential applications in controlled drug release systems.

Update on Phytochemistry and Pharmacology of Naturally Occurring Resveratrol Oligomers.

Resveratrol oligomers (REVs), a major class of stilbenoids, are biosynthesized by regioselective oxidative coupling of two to eight units of resveratrol monomer. Due to their unique structures and pleiotropic biological activities, natural product chemists are increasingly focusing on REVs in the last few decades. This study presents a detailed and thorough examination of REVs, including chemical structures, natural resources, and biological activities, during the period of 2010-2017. Ninety-two new REVs compounds, including 39 dimers, 23 trimers, 13 tetramers, six resveratrol monomers, six hexamers, four pentamers, and one octamer, have been reported from the families of Dipterocarpaceae, Paeoniaceae, Vitaceae, Leguminosae, Gnetaceae, Cyperaceae, Polygonaceae Gramineae, and Poaceae. Amongst these families, Dipterocarpaceae, with 50 REVs, accounts for the majority, and seven genera of Dipterocarpaceae are involved, including Vatica, Vateria, Shorea, Hopea, Neobalanocarpus, Dipterocarpus, and Dryobalanops. These REVs have shown a wide range of bioactivities. Pharmacological studies have mainly focused on potential efficacy on tumors, bacteria, Alzheimer's disease, cardiovascular diseases, and others. The information updated in this review might assist further research and development of novel REVs as potential therapeutic agents.

The effects of combined human parathyroid hormone (1-34) and simvastatin treatment on the interface of hydroxyapatite-coated titanium rods implanted into osteopenic rats femurs.

The effect of human parathyroid hormone 1-34 (PTH) and simvastatin (SIM) alone could promote bone healing in osteoporotic implant fixation, but there are no reports about the combined use of PTH and SIM for promotion of bone healing around implant in osteoporotic settings. This study aims to investigate effects of PTH + SIM on implant stabilization in osteopenic rats. Fourteen weeks after chronically fed a low protein diet, osteopenic rats randomly received implants. Subsequently, the animals were randomly divided into four groups: Control, SIM, PTH and PTH + SIM. Then all rats from groups PTH, SIM and PTH + SIM received PTH (40 µg/kg, three times a week), SIM (25 mg/kg, daily), or both for 12 weeks. The results of our study indicated that all treatments promoted bone healing around implant compared to Control, but PTH + SIM treatment showed significantly stronger effects than PTH or SIM alone in histological, micro-CT, and biomechanical tests. The results indicated additive effects of PTH and SIM on implant fixation in osteoporotic rats.

Percutaneous Curved Vertebroplasty Decrease the Risk of Cemented Vertebra Refracture Compared with Bilateral Percutaneous Kyphoplasty in the Treatment of Osteoporotic Vertebral Compression Fractures.

Purpose: The purpose of this study is to compare the refracture rate of the cemented vertebral body of percutaneous curved vertebroplasty (PCVP) and bilateral percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures (OVCF). Methods: Ninety-four patients with single segment thoracolumbar OVCF were randomly divided into two groups (47 patients in each) and underwent PCVP or bilateral PKP surgery, respectively. Refracture of cemented vertebral body, bone cement injection volume and cement pattern, cement leakage rate, total surgical time, intraoperative fluoroscopy time, preoperative and postoperative Cobb angles and anterior vertebral height, Oswestry disability index questionnaire (ODI) and visual analog scales (VAS) were recorded. Results: The PCVP group had significantly lower refracture incidence of the cemented vertebral than the bilateral PKP group (p<0.05). There was a significant postoperative improvement in the VAS score and ODI in both group (p<0.01), and no significant difference was found between two groups. The operation time and intraoperative fluoroscopy times were significantly less in the PCVP group than in the bilateral PKP group (p<0.01). The mean kyphosis angle correction and vertebral height restoration in the PCVP group was significantly less than that in the bilateral PKP group (p<0.01). Conclusion: Both PCVP and PKP were safe and effective treatments for OVCF. The PCVP had lower refracture rate of the cemented vertebral than the bilateral PKP group, and PCVP entailed less exposure to fluoroscopy and shorter operation time than bilateral PKP.

Establishment of an Efficient Protoplast Isolation and Transfection Method for Eucommia ulmoides Oliver.

BACKGROUND: Eucommia ulmoides Oliver is a unique high-quality natural rubber tree species and rare medicinal tree species in China. The rapid characterization of E. ulmoides gene function has been severely hampered by the limitations of genetic transformation methods and breeding cycles. The polyethylene glycol (PEG)-mediated protoplast transformation system is a multifunctional and rapid tool for the analysis of functional genes in vivo, but it has not been established in E. ulmoides. METHODS: In this study, a large number of highly active protoplasts were isolated from the stems of E. ulmoides seedlings by enzymatic digestion, and green fluorescent protein expression was facilitated using a PEG-mediated method. RESULTS: Optimal enzymatic digestion occurred when the enzyme was digested for 10 h in an enzymatic solution containing 2.5% Cellulase R-10 (w/v), 0.6% Macerozyme R-10 (w/v), 2.5% pectinase (w/v), 0.5% hemicellulase (w/v), and 0.6 mol/L mannitol. The active protoplast yield under this condition was 1.13 × 106 protoplasts/g fresh weight, and the protoplast activity was as high as 94.84%. CONCLUSIONS: This study established the first protoplasm isolation and transient transformation system in hard rubber wood, which lays the foundation for subsequent functional studies of E. ulmoides genes to achieve high-throughput analysis, and provides a reference for future gene function studies of medicinal and woody plants.

Hepcidin expression levels involve efficacy of pegylated interferon-α treatment in hepatitis B-infected liver.

BACKGROUND: Hepcidin is the master iron regulator hormone produced by the liver. The association of serum hepcidin with pegylated interferon therapy in patients with chronic hepatitis C infection has been studied. However, the role of serum hepcidin level in predicting the effect of pegylated interferon treatment in patients with chronic hepatitis B (CHB) infection is yet to be elucidated. Our study aims to investigate the correlation between hepcidin expression levels and the curative effect of interferon-alpha therapy in patients with CHB. METHODS: A total of 47 patients with CHB who accepted pegylated interferon-α (PEG-IFN- α) treatment were recruited. The serum level of hepcidin was estimated by ELISA. The alternation in the gene expression level of hepcidin was detected by RT-PCR, and immunofluorescence cell staining was performed to detect hepcidin peptide. The induction of antiviral proteins was analyzed by Western blotting. The predictive value of early on-treatment variation in serum hepcidin during treatment progress was assessed by receiver operating characteristic analysis. RESULTS: High levels of early on-treatment serum hepcidin were observed in patients who achieved a decline in HBsAg > 1 log10 IU/mL or HBV DNA > 1 log10 IU/mL. In vitro, an elevation of the hepcidin expression in HepG2.2.15 cells induced by PEG-IFN-α treatment was noted. Furthermore, combined treatment with hepcidin and PEG-IFN-α increased the levels of antiviral proteins. The predictive cut-off value of hepcidin for HBsAg decline > 1 log10 IU/mL was 239 pg/mL, and the sensitivity and specificity were 72.73% and 70.97%, respectively. The predictive cut-off value of hepcidin for the decline in HBV DNA > 1 log10 IU/mL was 190.4 pg/mL, and the sensitivity and specificity were 72.73% and 61.11%, respectively. Early-on treatment changes in the hepcidin level signified the predictive value of the PEG-IFN-α curative effect. CONCLUSIONS: A higher early-on treatment hepcidin level indicates a higher possibility of HBsAg and HBV DNA decline in patients with CHB during PEG-IFN-α treatment. A high early-on treatment serum hepcidin level is significant in predicting the PEG-IFN-α therapeutic effect in patients with CHB.

Evaluating Craniovertebral Stability in Chiari Malformation Coexisting with Type II Basilar Invagination: An Observational Study Based on Kinematic Computed Tomography and Its Clinical Application.

BACKGROUND: Treatment of Chiari malformation (CM) is controversial, especially when it coexists with "stable" or Type II basilar invagination (CM + II-BI). Precise evaluation of craniovertebral junction (CVJ) stability is crucial in such patients; however, this has never been validated. This study aimed to dynamically evaluate atlanto-condyle and atlantoaxial stability by kinematic computed tomography (CT) and report its surgical treatment. METHODS: The study recruited 101 patients (control, CM, and CM + II-BI groups: 48, 34, and 19 patients, respectively). During kinematic CT, the CVJ stability-related parameters were measured and compared between the 3 groups. The surgical strategy for treating CM + II-BI was based on these results. Preoperative and postoperative images were acquired, and functional scores were used to assess the outcome. RESULTS: Among the 3 groups, the length of the clivus and the height of the condyle were the shortest in the CM + II-BI group, which was accompanied by the greatest rotation of the atlas and atlanto-condyle facet movement on cervical flexion and extension. Moreover, in such patients, increased Chamberlain's baseline violation indicated the aggregate invagination of the odontoid in the flexed position, and asymmetric displacement of atlantoaxial facets was observed. Seventeen CM + II-BI patients underwent surgical treatment with atlantoaxial distraction and occipitocervical fusion. The syringomyelia width and tonsillar herniation decreased significantly, and functional scores indicated symptom relief and good outcomes. CONCLUSIONS: CVJ instability, especially the ultramovement of atlanto-condyle facets, commonly exists in II-BI as evaluated using kinematic CT. The surgical strategy of atlantoaxial distraction and occipitocervical fusion should be considered to treat such patients.

The infectivity and pathogenicity of a foot-and-mouth disease virus persistent infection strain from oesophageal-pharyngeal fluid of a Chinese cattle in 2010.

BACKGROUND: Foot-and mouth disease (FMD) is an acute, febrile, and contagious vesicular disease affecting cloven-hoofed animals. Some animals may become persistent infected carriers when they contact FMD virus (FMDV), and persistent infected animals are a dangerous factor to cause FMD outbreak. FINDINGS: 300 OP (oesophageal-pharyngeal) fluid samples were collected from cattle without clinic symptom after one month FMD circulated in 2010 in China. A FMDV strain was isolated when a positive OP sample was passed in BHK21 cell line. The strain, named O/CHN/2010/33-OP, was detected to be O/Myanmar/1998 lineage with VP1 DNA sequence comparison. In order to testify its infectivity, two cattle were challenged with OP fluid and three pigs were put into the same pen for direct contact infection. The result showed that one of the cattle and one of the pigs appeared FMD clinic symptoms respectively. Furthermore, two cattle (three pigs were also put into the same pen for direct contact infection) and three pigs were inoculated with O/CHN/2010/33-OP cell passaged strain. The result showed that one of the challenged pigs appeared FMD clinic symptoms. Two cattle and three pigs in the same pen did not appeared FMD clinic symptoms, but the sera antibody and their OP fluid of two cattle were positive. Meanwhile, the spinal cords of three pigs in the same pen with two cattle were positive detected with multiplex- RT-PCR. CONCLUSION: The persistent infection strain O/CHN/2010/33-OP has infectivity and pathogenicity to cattle and pigs, and infected cattle may transmit the virus to pigs although its virulence was lower than the circulated strain O/CHN/Mya98/2010.

Estrogen deficiency leads to impaired osteogenic differentiation of periodontal ligament stem cells in rats.

Estrogen deficiency in post-menopausal women is considered as one of the risk factors for periodontal diseases. The periodontal ligament is a connective tissue that connects cementum and alveolar bone to constrain teeth within the jaw. Periodontal ligament stem cells (PDLSCs) isolated from the periodontal ligament can differentiate into many types of specialized cells, including osteoblast-like cells that can be used to regenerate alveolar bone. However, little is known about the effect of estrogen-deficient microenvironment on the osteogenic differentiation of PDLSCs. The aim of this study was to explore the role of estrogen on the potential for osteogenic differentiation of PDLSCs using a rat model of osteoporosis. Three-month-old female Sprague-Dawley rats were divided into two groups (n = 6 for each): ovariectomized (OVX) and sham-operated rats (Sham). Then the characteristics of PDLSCs isolated from these rats were investigated. Real-time PCR analysis showed the lower expression levels of estrogen receptors (ERα and ERß) mRNAs in PDLSCs of OVX animals compared to Sham control. Mineralization assay demonstrated fewer calcium deposits in PDLSCs from OVX group than those from Sham group. Treatment with 17ß-estradiol (E2) significantly enhanced the osteogenic differentiation of PDLSCs from both groups in vitro. Furthermore, by means of lentivirus-mediated siRNA targeting ERα or ERß, the expression of ERα or ERß was down-regulated (> 50% reduction), which impaired the estrogen-induced osteogenic differentiation of PDLSCs from both groups (> 50% reduction). These results indicate that estrogen plays an important role in maintaining osteogenic differentiation of PDLSCs, which acts through both ERα and ERß.

Adjuvant interferon therapy for malignant melanoma: the debate.

Based on the results of the Kirkwood high-dose interferon alpha-2b (HDI) adjuvant therapy trial of the Eastern Cooperative Oncology Group 1684, the US Food and Drug Administration (FDA) approved HDI as the postoperative adjuvant therapy for high-risk melanoma. Unfortunately, controversies continue regarding the use of interferon (IFN) as adjuvant therapy for melanoma owing to the inconsistent results of subsequent trials. Numerous trials of adjuvant interferon therapy demonstrated a benefit in terms of relapse-free survival (RFS), but without confirmed significant effect on overall survival (OS). The optimal timing, dose, and type of interferon are not yet defined. Therefore, adjuvant interferon treatment is preferentially applied in the randomized clinical trials in specialized centers. Decisions about the appropriateness of adjuvant interferon alfa-2b treatment for patients should be made on an individual basis, after discussion with the patient, including an explanation of the potential benefits and side effects of interferon therapy. Moreover, we also need to use available regimens reasonably, seek feasible and predictable prognostic factors to serve patients with individualized therapy.

Self-enriched mesoporous silica nanoparticle composite membrane with remarkable photodynamic antimicrobial performances.

Mesoporous silica nanoparticle (MSN) demonstrates great potentials as a loading platform for bactericidal agents, but may be limited by its application form of bulk or powder. Herein, we developed MSN surface-enriched composite membranes with remarkable photodynamic antimicrobial activities via a facile electrospinning method. The mixture of zein and polycaprolactone (PCL) was served as the polymeric matrix, while the methylene blue (MB) loaded MSN was modified by trichloro (1H, 1H, 2H, 2H-heptadecafluorodecyl) silane (THFS) and acted as reactive oxygen species (ROS) generator to exert their antimicrobial performances. Owing to its low surface energy, the fluorinated MSN tended to be enriched on the surface of the nanofiber, hence significantly enhancing the ROS generation. Moreover, benefiting from the surface enrichment of the fluorinated nanoparticles, the composite membrane displayed obvious surface hydrophobicity and exhibited discernible bacterial repellency. Subsequently, upon visible light (660 nm) irradiation, the composite membrane demonstrated remarkable photodynamic antibacterial activities against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) but without essential detrimental impacts on the mammalian cells. We envision that this self-enriched MSN composite membrane may find broad applications in bacterial infection-resistant areas.

Characterization of an Electronic Corneal Prosthesis System.

PURPOSE: Corneal opacity is a leading cause of reversible blindness worldwide. An electronic corneal prosthesis, or intraocular projector, could potentially restore high-quality vision without need for corneal clarity. MATERIALS AND METHODS: Four intraocular projection systems were constructed from commercially available electronic components and encased in biocompatible plastic housing. They were tested for optical properties, biocompatibility, heat dissipation, waterproofing, and accelerated wear. A surgical implantation technique was developed. RESULTS: Intraocular projectors were produced of a size that can fit within the eye. Their optics produce better than 20/200 equivalent visual acuity. MTT assay demonstrated no cytotoxicity of devices in vitro. Temperature testing demonstrated less than 2°C increase in temperature after 1 h. Three devices lasted over 12 weeks under accelerated wear conditions. Implantation surgery was demonstrated via corneal trephination insertion in a cadaver eye. CONCLUSION: This is the first study to demonstrate and characterize fully functional intraocular projection systems. This technology has the potential to be an important new tool in the treatment of intractable corneal blindness.

Ultrasmall Oxygen-Deficient Bimetallic Oxide MnWOX Nanoparticles for Depletion of Endogenous GSH and Enhanced Sonodynamic Cancer Therapy.

Sonodynamic therapy (SDT) triggered by ultrasound (US) has attracted increasing attention owing to its abilities to overcome critical limitations including low tissue-penetration depth and phototoxicity in photodynamic therapy. Herein, the design of a new type of sonosensitizer is revealed, namely, ultrasmall oxygen-deficient bimetallic oxide MnWOX nanoparticles, for multimodal imaging-guided enhanced SDT against cancer. As-made MnWOX nanoparticles with poly(ethylene glycol) (PEG) modification show high physiological stability and biocompatibility. Interestingly, such MnWOX -PEG nanoparticles exhibit highly efficient US-triggered production of 1 O2 and •OH, higher than that of previously reported sonosensitizers (e.g., protoporphyrin IX and titanium dioxide), because the oxygen-deficient structure of MnWOX serves as an electron trap site to prevent electron-hole recombination. The glutathione depletion capability of MnWOX -PEG can also further favor SDT-triggered cancer cell killing. With efficient tumor homing as illustrated by computer tomography and magnetic resonance imaging, MnWOX -PEG enables effective destruction of mouse tumors under US stimulation. After accomplishing its therapeutic functions, MnWOX -PEG can be metabolized by the mouse body without any long-term toxicity. Herein, a new type of sono-sensitizing agent with high SDT efficacy, multimodal imaging functions, and rapid clearance is presented, an agent which is promising for noninvasive SDT cancer treatment.

Photosensitive Hydrogel Creates Favorable Biologic Niches to Promote Spinal Cord Injury Repair.

Photochemistry is considered to be a promising strategy for hydrogels to mimic the complex and dynamic properties of natural extracellular matrix. However, it is seldom applied in 3D tissue engineering and regenerative medicine due to the attenuation of light. In this study, phenyl azide photchemistry and optical fiber technology are first used to localize adhesive protein on the inner surface of the nerve guidance conduit in a 3D hydrogel scaffold. In vitro coculture assay of neural stem cells (NSCs) shows that photoimmobilization of collagen significantly improves the adhesion and survival of NSCs in the conduit, and exhibits synergistic effect with the sustainable release of growth factor. After implantation in transected spinal cord, the optimized hydrogel scaffold is found to improve the locomotion recovery of rats 12 weeks after spinal cord injury (SCI). Histological analysis suggests that the designed hydrogel scaffold provides a favorable biological niche for neuronal regeneration, thus producing directional neuron tissue and promoting the repair of SCI. This study demonstrates a promising hydrogel scaffold for SCI repair and provides the first understanding of the photoimmobilization of adhesive protein in a 3D hydrogel conduit concerning its functions on spinal cord tissue restoration.

The fast degradation of ß-TCP ceramics facilitates healing of bone defects by the combination of BMP-2 and Teriparatide.

Accumulating evidence suggests that the degradation and resorption of calcium phosphate ceramics is always relatively slow, which may inhibit calcium phosphate ceramics' replacement by new bone tissues and the ultimate bone defect repair. Bone morphogenetic proteins (BMPs) and Teriparatide (PTH) are extensively applied in the treatment of bone pathologies, while their effects on the degradation of calcium phosphate ceramics is limited. In this study, we tested the effects of BMP and PTH on degradation of ß-tricalcium phosphate (ß-TCP) ceramics and bone formation on ß-TCP in ovariectomized (OVX) rat models. After establishment of femur defect model on OVX rats, the BMP + PTH group's rats were injected Teriparatide (30 µg/kg) subcutaneous every other day, while rats of control group and group BMP were injected equal-to-group volume sterilized saline water. Twelve weeks after femur surgery, all rats were sacrificed for Micro-CT scanning and histology tests. The results showed that BMP facilitated degradation of ß-TCP and new bone formation on ß-TCP ceramics. And PTH showed an additional effect on degradation of ß-TCP when combined with BMP. In addition, the results explained that PTH promoted the remodeling of the bone callus occurred during repair.

Digital quantification of gene methylation in stool DNA by emulsion-PCR coupled with hydrogel immobilized bead-array.

Aberrations of gene methylation in stool DNA (sDNA) is an effective biomarker for non-invasive colorectal cancer diagnosis. However, it is challenging to accurately quantitate the gene methylation levels in sDNA due to the low abundance and degradation of sDNA. In this study, a digital quantification strategy was proposed by combining emulsion PCR (emPCR) with hydrogel immobilized bead-array. The assay includes following steps: bisulfite conversion of sDNA, pre-amplification by PCR with specific primers containing 5' universal sequences, emPCR of pre-amplicons with beaded primers to achieve single-molecular amplification and identification of hydrogel embedding beads coated with amplicons. The sensitivity and the specificity of the method are high enough to pick up 0.05% methylated targets from unmethylated DNA background. The successful detection of hypermethylated vimentin gene in clinical stool samples suggests that the proposed method should be a potential tool for non-invasive colorectal cancer screening.

An interpenetrating network-strengthened and toughened hydrogel that supports cell-based nucleus pulposus regeneration.

Hydrogel is a suitable scaffold for the nucleus pulposus (NP) regeneration. However, its unmatched mechanical properties lead to implant failure in late-stage disc degeneration because of structural failure and implant extrusion after long-term compression. In this study, we evaluated an interpenetrating network (IPN)-strengthened and toughened hydrogel for NP regeneration, using dextran and gelatin as the primary network while poly (ethylene glycol) as the secondary network. The aim of this study was to realize the NP regeneration using the hydrogel. To achieve this, we optimized its properties by adjusting the mass ratios of the secondary/primary networks and determining the best preparation conditions for NP regeneration in a series of biomechanical, cytocompatibility, tissue engineering, and in vivo study. We found the optimal formulation of the IPN hydrogel, at a secondary/primary network ratio of 1:4, exhibited high toughness (the compressive strain reached 86%). The encapsulated NP cells showed increasing proliferation, cell clustering and matrix deposition. Furthermore, the hydrogel could support long-term cell retention and survival in the rat IVDs. It facilitated rehydration and regeneration of porcine degenerative NPs. In conclusion, this study demonstrates the tough IPN hydrogel could be a promising candidate for functional disc regeneration in future.