A xonotlite nanofiber bioactive 3D-printed hydrogel scaffold based on osteo-/angiogenesis and osteoimmune microenvironment remodeling accelerates vascularized bone regeneration.

BACKGROUND: Coordination between osteo-/angiogenesis and the osteoimmune microenvironment is essential for effective bone repair with biomaterials. As a highly personalized and precise biomaterial suitable for repairing complex bone defects in clinical practice, it is essential to endow 3D-printed scaffold the above key capabilities. RESULTS: Herein, by introducing xonotlite nanofiber (Ca6(Si6O17) (OH)2, CS) into the 3D-printed silk fibroin/gelatin basal scaffold, a novel bone repair system named SGC was fabricated. It was noted that the incorporation of CS could greatly enhance the chemical and mechanical properties of the scaffold to match the needs of bone regeneration. Besides, benefiting from the addition of CS, SGC scaffolds could accelerate osteo-/angiogenic differentiation of bone mesenchymal stem cells (BMSCs) and meanwhile reprogram macrophages to establish a favorable osteoimmune microenvironment. In vivo experiments further demonstrated that SGC scaffolds could efficiently stimulate bone repair and create a regeneration-friendly osteoimmune microenvironment. Mechanistically, we discovered that SGC scaffolds may achieve immune reprogramming in macrophages through a decrease in the expression of Smad6 and Smad7, both of which participate in the transforming growth factor-ß (TGF-ß) signaling pathway. CONCLUSION: Overall, this study demonstrated the clinical potential of the SGC scaffold due to its favorable pro-osteo-/angiogenic and osteoimmunomodulatory properties. In addition, it is a promising strategy to develop novel bone repair biomaterials by taking osteoinduction and osteoimmune microenvironment remodeling functions into account.

Quercetin-loaded mesoporous nano-delivery system remodels osteoimmune microenvironment to regenerate alveolar bone in periodontitis via the miR-21a-5p/PDCD4/NF-κB pathway.

BACKGROUND: Impaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in the pathogenesis of the alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack of ideal therapeutic strategies for periodontitis that can regenerate the alveolar bone while remodeling the osteoimmune microenvironment. Quercetin, as a monomeric flavonoid, has multiple pharmacological activities, such as pro-regenerative, anti-inflammatory, and immunomodulatory effects. Despite its vast spectrum of pharmacological activities, quercetin's clinical application is limited due to its poor water solubility and low bioavailability. RESULTS: In this study, we fabricated a quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with the function of continuously releasing quercetin, which could better promote the bone regeneration and regulate the immune microenvironment in the alveolar bone defect with periodontitis compared to pure MBG treatment. In particular, this nano-delivery system effectively decreased injection frequency of quercetin while yielding favorable therapeutic results. In view of the above excellent therapeutic effects achieved by the sustained release of quercetin, we further investigated its therapeutic mechanisms. Our findings indicated that under the periodontitis microenvironment, the intervention of quercetin could restore the osteo-/angiogenic capacity of periodontal ligament stem cells (PDLSCs), induce immune regulation of macrophages and exert an osteoimmunomodulatory effect. Furthermore, we also found that the above osteoimmunomodulatory effects of quercetin via macrophages could be partially blocked by the overexpression of a key microRNA--miR-21a-5p, which worked through inhibiting the expression of PDCD4 and activating the NF-κB signaling pathway. CONCLUSION: In summary, our study shows that quercetin-loaded mesoporous nano-delivery system has the potential to be a therapeutic approach for reconstructing alveolar bone defects in periodontitis. Furthermore, it also offers a new perspective for treating alveolar bone defects in periodontitis by inhibiting the expression of miR-21a-5p in macrophages and thereby creating a favorable osteoimmune microenvironment.

Deciphering Molecular Mechanism Underlying Self-Flocculation of Zymomonas mobilis for Robust Production.

Zymomonas mobilis metabolizes sugar anaerobically through the Entner-Doudoroff pathway with less ATP generated for lower biomass accumulation to direct more sugar for product formation with improved yield, making it a suitable host to be engineered as microbial cell factories for producing bulk commodities with major costs from feedstock consumption. Self-flocculation of the bacterial cells presents many advantages, such as enhanced tolerance to environmental stresses, a prerequisite for achieving high product titers by using concentrated substrates. ZM401, a self-flocculating mutant developed from ZM4, the unicellular model strain of Z. mobilis, was employed in this work to explore the molecular mechanism underlying this self-flocculating phenotype. Comparative studies between ZM401 and ZM4 indicate that a frameshift caused by a single nucleotide deletion in the poly-T tract of ZMO1082 fused the putative gene with the open reading frame of ZMO1083, encoding the catalytic subunit BcsA of the bacterial cellulose synthase to catalyze cellulose biosynthesis. Furthermore, the single nucleotide polymorphism mutation in the open reading frame of ZMO1055, encoding a bifunctional GGDEF-EAL protein with apparent diguanylate cyclase/phosphodiesterase activities, resulted in the Ala526Val substitution, which consequently compromised in vivo specific phosphodiesterase activity for the degradation of cyclic diguanylic acid, leading to intracellular accumulation of the signaling molecule to activate cellulose biosynthesis. These discoveries are significant for engineering other unicellular strains from Z. mobilis with the self-flocculating phenotype for robust production. IMPORTANCE Stress tolerance is a prerequisite for microbial cell factories to be robust in production, particularly for biorefinery of lignocellulosic biomass to produce biofuels, bioenergy, and bio-based chemicals for sustainable socioeconomic development, since various inhibitors are released during the pretreatment to destroy the recalcitrant lignin-carbohydrate complex for sugar production through enzymatic hydrolysis of the cellulose component, and their detoxification is too costly for producing bulk commodities. Although tolerance to individual stress has been intensively studied, the progress seems less significant since microbial cells are inevitably suffering from multiple stresses simultaneously under production conditions. When self-flocculating, microbial cells are more tolerant to multiple stresses through the general stress response due to enhanced quorum sensing associated with the morphological change for physiological and metabolic advantages. Therefore, elucidation of the molecular mechanism underlying such a self-flocculating phenotype is significant for engineering microbial cells with the unique multicellular morphology through rational design to boost their production performance.

Anemoside B4 inhibits enterovirus 71 propagation in mice through upregulating 14-3-3 expression and type I interferon responses.

Enterovirus 71 (EV71) is the major pathogens of human hand, foot, and mouth disease (HFMD). EV71 efficiently escapes innate immunity responses of the host to cause infection. At present, no effective antiviral drugs for EV71 are available. Anemoside B4 (B4) is a natural saponin isolated from the roots of Pulsatilla chinensis (Bunge) Regel. P. chinensis extracts that shows a wide variety of biological activities. In this study, we investigated the antiviral activities of B4 against EV71 both in cell culture and in suckling mice. We showed that B4 (12.5-200 µM) dose dependently increased the viability of EV71-infected RD cells with an IC50 value of 24.95 ± 0.05 µM against EV71. The antiviral activity of B4 was associated with enhanced interferon (IFN)-ß response, since knockdown of IFN-ß abolished its antiviral activity. We also confirmed that the enhanced IFN response was mediated via activation of retinoic acid-inducible gene I (RIG-I) like receptors (RLRs) pathway, and it was executed by upregulation of 14-3-3 protein, which disrupted the interaction between yes-associated protein (YAP) and interferon regulatory factor 3 (IRF3). By using amino acids in cell culture (SILAC)-based proteomics profiling, we identified the Hippo pathway as the top-ranking functional cluster in B4-treated EV71-infected cells. In vivo experiments were conducted in suckling mice (2-day-old) infected with EV71 and subsequently B4 (200 mg · kg-1 · d-1, i.p.) was administered for 16 days. We showed that B4 administration effectively suppressed EV71 replication and improved muscle inflammation and limb activity. Meanwhile, B4 administration regulated the expressions of HFMD biomarkers IL-10 and IFN-γ, attenuating complications of EV71 infection. Collectively, our results suggest that B4 could enhance the antiviral effect of IFN-ß by orchestrating Hippo and RLRs pathway, and B4 would be a potential lead compound for developing an anti-EV71 drug.

Highly Selective Capture of Monophosphopeptides by Two-Dimensional Metal-Organic Framework Nanosheets.

Separation of monophosphopeptides from multi-phosphopeptides in complex biological samples is significant in the study of protein kinase signal transduction pathways. To the best of our knowledge, very few materials have been reported that could selectively enrich monophosphopeptides because of the chemical difficulty in retaining the intermediate monophosphopeptides and excluding both non-phosphopeptides and multi-phosphopeptides in acidic conditions, which requires unique interactions to balance the metallic affinity and the hydrophobicity. With the large surface area, abundant accessible active sites, and ultrathin structures, two-dimensional (2-D) metal-organic framework (MOF) Hf-1,3,5-tris(4-carboxyphenyl)benzene (BTB) nanosheets were rationally selected. Due to the elongated organic ligands and the balance between metallic affinity of clusters and hydrophobicity from ligands, the 2-D Hf-BTB nanosheets exhibited unique enrichment selectivity toward monophosphopeptides. The 2-D MOF nanosheets demonstrated excellent sensitivity (detection limit of 0.4 fmol µL-1) and selectivity [1:1000 molar ratios of ß-casein/BSA (bovine serum albumin)] in model phosphopeptides enrichment. The nanosheets were implemented for the analysis of nonfat milk and human saliva samples as well as in situ isotope labeling for dysregulated phosphopeptides from patients' serum with anal canal inflammation, exhibiting 6.6-fold upregulation of serum phosphopeptide HS4 (ADpSGEGDFLAEGGGVR) compared to the control healthy serum. The proteomics analysis of mouse brain cortical samples associated with Alzheimer's disease, which were from Akt (protein kinase B) conditional knockout mouse and littermate control mouse, was further established with 2-D Hf-BTB nanosheets. With high capture efficiency for monophosphopeptides, this method was capable of distinguishing the difference of monophosphopeptides from microtubule-associated protein τ (MAPT/τ) between the Akt knockout sample and control sample.

Barbaloin loaded polydopamine-polylactide-TPGS (PLA-TPGS) nanoparticles against gastric cancer as a targeted drug delivery system: Studies in vitro and in vivo.

Gastric cancer is the third leading cause of cancer-associated death worldwide. Although a decrease in its incidence is observed, gastric cancer still poses a major clinical challenge due to poor prognosis and limited treatments. Barbaloin (BBL) is a main medicinal composition of the Chinese traditional medicine aloe vera. BBL has various bioactivities, including anti-oxidant, anti-inflammatory and anti-tumor properties. Polydopamine (pD)-based surface modification is easy to functionalize polymeric nanoparticles (NPs) surfaces with ligands and/or additional polymeric layers. In the present study, BBL-loaded formulations was developed with pD-modified NPs, which was synthesized by polylactide-TPGS (PLA-TPGS) (pD-PLA-TPGS/NPs). And galactosamine (Gal) was conjugated on the prepared NPs (Gal-pD-PLA-TPGS/NPs) for targeting the gastric cancer cells. Here, we found that BBL-loaded Gal-pD-PLA-TPGS/NPs showed the highest cellular uptake efficacy in gastric cancer cells. Gal-pD-PLA-TPGS/NPs more significantly reduced the gastric cancer cell viability. Further, greater apoptosis, autophagy and ROS generation was induced by Gal-pD-PLA-TPGS/NPs in gastric cancer cells. Additionally, compared to the other two NPs, Gal-pD-PLA-TPGS/NPs most markedly decreased ATP levels in gastric cancer cells. In vivo, Gal-pD-PLA-TPGS/NPs were specifically targeted to tumor site. Moreover, Gal-pD-PLA-TPGS/NPs exhibited the most anti-tumor effects, as evidenced by the lowest tumor volume and tumor weight. Of note, there was no significant difference was observed in body and liver weight, as well as the histological changes in major organs isolated from each group of mice. Together, the findings indicated that BBL-loaded Gal-pD-PLA-TPGS/NPs could be targeted to gastric cancer cells to suppress tumor progression without toxicity.

Anaerobic biodegradation of partially hydrolyzed polyacrylamide in long-term methanogenic enrichment cultures from production water of oil reservoirs.

The increasing usage of partially hydrolyzed polyacrylamide (HPAM) in oilfields as a flooding agent to enhance oil recovery at so large quantities is an ecological hazard to the subsurface ecosystem due to persistence and inertness. Biodegradation of HPAM is a potentially promising strategy for dealing with this problem among many other methods available. To understand the responsible microorganisms and mechanism of HPAM biodegradation under anaerobic conditions, an enrichment culture from production waters of oil reservoirs were established with HPAM as the sole source of carbon and nitrogen incubated for over 328 days, and analyzed using both molecular microbiology and chemical characterization methods. Gel permeation chromatography, High-pressure liquid chromatography and Fourier-transformed infrared spectroscopy results indicated that, after 328 days of anaerobic incubation, some of the amide groups on HPAM were removed and released as ammonia/ammonium and carboxylic groups, while the carbon backbone of HPAM was converted to smaller polymeric fragments, including oligomers and various fatty acids. Based on these results, the biochemical process of anaerobic biodegradation of HPAM was proposed. The phylogenetic analysis of 16S rRNA gene sequences retrieved from the enrichments showed that Proteobacteria and Planctomycetes were the dominant bacteria in the culture with HPAM as the source of carbon and nitrogen, respectively. For archaea, Methanofollis was more abundant in the anaerobic enrichment. These results are helpful for understanding the process of HPAM biodegradation and provide significant insights to the fate of HPAM in subsurface environment and for possible bioremediation.

Selective Activation of Nociceptor TRPV1 Channel and Reversal of Inflammatory Pain in Mice by a Novel Coumarin Derivative Muralatin L from Murraya alata.

Coumarin and its derivatives are fragrant natural compounds isolated from the genus Murraya that are flowering plants widely distributed in East Asia, Australia, and the Pacific Islands. Murraya plants have been widely used as medicinal herbs for relief of pain, such as headache, rheumatic pain, toothache, and snake bites. However, little is known about their analgesic components and the molecular mechanism underlying pain relief. Here, we report the bioassay-guided fractionation and identification of a novel coumarin derivative, named muralatin L, that can specifically activate the nociceptor transient receptor potential vanilloid 1 (TRPV1) channel and reverse the inflammatory pain in mice through channel desensitization. Muralatin L was identified from the active extract of Murraya alata against TRPV1 transiently expressed in HEK-293T cells in fluorescent calcium FlexStation assay. Activation of TRPV1 current by muralatin L and its selectivity were further confirmed by whole-cell patch clamp recordings of TRPV1-expressing HEK-293T cells and dorsal root ganglion neurons isolated from mice. Furthermore, muralatin L could reverse inflammatory pain induced by formalin and acetic acid in mice but not in TRPV1 knock-out mice. Taken together, our findings show that muralatin L specifically activates TRPV1 and reverses inflammatory pain, thus highlighting the potential of coumarin derivatives from Murraya plants for pharmaceutical and medicinal applications such as pain therapy.

Comparative proteomic analysis provides insight into 10-hydroxy-2-decenoic acid biosynthesis in honey bee workers.

10-Hydroxy-2-decenoic acid (10-HDA) is the major compound produced from the mandibular glands (MGs) of honey bee workers. However, little information is available on the molecular mechanisms of 10-HDA biosynthesis. In our study, based on investigating the 10-HDA secretion pattern and the morphological characteristics of MGs from honey bee workers of different ages, a comparative proteomic analysis was performed in the MGs of workers with different 10-HDA production. In total, 59 up-regulated protein species representing 45 unique proteins were identified in high 10-HDA-producing workers by 2-DE-MALDI-TOF/TOF MS. These proteins were involved in carbohydrate/energy metabolism, fatty acid metabolism, protein metabolism and folding, antioxidation, cytoskeleton, development and cell signaling. Proteins related to fatty acid metabolism, including fatty acid synthase and ß-oxidation enzymes, are potentially crucial proteins involved in 10-HDA biosynthesis pathway. And RNA interference (RNAi) results demonstrated that knockdown of electron transfer flavoprotein subunit beta (ETF-ß), one of the protein related to fatty acid metabolism, decreased 10-HDA production of worker bees, suggesting that ETF-ß was necessary for 10-HDA biosynthesis. This study reveals the characteristics of MGs of worker bees at different developmental stages and proteins associated with 10-HDA biosynthesis, which provides the first insight into the molecular mechanism of 10-HDA biosynthesis.

Novel POSS-PCU Nanocomposite Material as a Biocompatible Coating for Quantum Dots.

Quantum dots (QDs) are fluorescent nanoparticles with unique photophysical properties that enable them to potentially replace traditional organic dyes and fluorescent proteins in various bioimaging applications. However, the inherent toxicity of their cores based on cadmium salts limits their widespread biomedical use. We have developed a novel nanocomposite polymer emulsion based on polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) that can be used to coat quantum dots to nullify their toxicity and enhance photostability. Here we report the synthesis and characterization of a novel POSS-PCU nanocomposite polymer emulsion and describe its application for coating QDs for biological application. The polymer was synthesized by a process of emulsion polymerization and formed stable micelles of ∼33 nm in diameter. CdTe/CdS/ZnS QDs were efficiently stabilized by the polymer emulsion through encapsulation within the polymer micelles. Characterization studies showed no significant change in the unique photophysical properties of QDs after coating. The polymer was biocompatible to HepG2, HUVECs, and mouse skeletal muscle cells at 2.5% after 24 h exposure on in vitro testing. Polymer encapsulated QDs showed enhanced photostability on exposure to high degrees of UV irradiation and air as well as significantly reduced cytotoxicity on exposure to HepG2 cells at 30 µg/mL for 24 h. We have therefore concluded that the POSS-PCU polymer emulsion has the potential to make a biocompatible and photostable coating for QDs enabling a host of biomedical applications to take this technology to the next level.

Theoretical and experimental research on the self-assembled system of molecularly imprinted polymers formed by salbutamol and methacrylic acid.

The quantum chemical method was applied for screening functional monomers in the rational design of salbutamol-imprinted polymers. Salbutamol was the template molecule, and methacrylic acid was the single functional monomer. The LC-WPBE/6-31G(d,p) method was used to investigate the geometry optimization, active sites, natural bond orbital charges, binding energies of the imprinted molecule, and solvation energy. The mechanism of action between salbutamol and methacrylic acid was also discussed. The theoretical results show that salbutamol interacts with functional monomers by hydrogen bonds, and the salbutamol-imprinted polymers with a ratio of 1:4 (salbutamol/methacrylic acid) in acetonitrile had the highest stability. The salbutamol-imprinted polymers were prepared by precipitation polymerization. The experimental results indicated that the maximum adsorption capacity for salbutamol toward molecularly imprinted polymers was 7.33 mg/g, and the molecularly imprinted polymers had a higher selectivity for salbutamol than for norepinephrine and terbutaline sulfate. Herein, the studies can provide theoretical and experimental references for the salbutamol molecular imprinted system.

Simultaneous type III congenital esophageal atresia and patent ductus arteriosus in a low-weight patient: A case report.

BACKGROUND: We report a low-birth-weight child (1.8 kg) with neonatal type III congenital esophageal atresia (CEA) combined with symptomatic patent ductus arteriosus (PDA). After comprehensive evaluation, esophageal anastomosis was performed on postnatal day 11 after excluding surgical contraindications, and arterial catheter ligation was performed at the same time. Concurrent surgery for CEA combined with PDA has not been clearly reported in the literature. CASE SUMMARY: We report a 6-day-old female child with type III CEA and PDA. The patient presented with foam at the mouth after birth, cough and shortness of breath after feeding. At another hospital, she was considered to have neonatal pneumonia, neonatal jaundice and congenital heart disease and transferred to our hospital. After iodine oil radiography of the esophagus and echocardiography we confirmed diagnosis of CEA and PDA. The diameter of the PDA was 8 mm, with obvious left to right shunting. We performed right rear extrapleural orificium fistula ligation and esophageal anastomosis, and ligation of PDA via left axilla straight incision after 5 d of hospitalization. The operations were successful, and the incision healed after 12 d, and the patient was discharged. We re-examined the patient 1 mo after surgery. She did not vomit when she ate rice flour. Esophageal angiography showed no stricture of the anastomotic stoma. The patient weighed 3.2 kg. CONCLUSION: For CEA patients with multiple risk factors, comprehensive, timely and accurate diagnosis and evaluation, and early treatment may improve prognosis.

Biomimicking covalent organic frameworks nanocomposite coating for integrated enhanced anticorrosion and antifouling properties of a biodegradable magnesium stent.

The utilization of biodegradable magnesium (Mg) alloys in the fabrication of temporary non-vascular stents is an innovative trend in biomedical engineering. However, the heterogeneous degradation profiles of these biomaterials, together with potential bacterial colonization that could precipitate infectious or stenotic complications, are critical obstacles precluding their widespread clinical application. In pursuit of overcoming these limitations, this study applies the principles of biomimicry, particularly the hydrophobic and anti-fouling characteristics of lotus leaves, to pioneer the creation of nanocomposite coatings. These coatings integrate poly-trimethylene carbonate (PTMC) with covalent organic frameworks (COFs), to modify the stent's surface property. The strategic design of the coating's topography, porosity, and self-polishing capabilities collectively aims to decelerate degradation processes and minimize biological adhesion. The protective qualities of the coatings were substantiated through rigorous testing in both in vitro dynamic bile tests and in vivo New Zealand rabbit choledochal models. Empirical findings from these trials confirmed that the implementation of COF-based nanocomposite coatings robustly fortifies Mg implantations, conferring heightened resistance to both biocorrosion and biofouling as well as improved biocompatibility within bodily environments. The outcomes of this research elucidate a comprehensive framework for the multifaceted strategies against stent corrosion and fouling, thereby charting a visionary pathway toward the systematic conception of a new class of reliable COF-derived surface modifications poised to amplify the efficacy of Mg-based stents. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium (Mg) alloys are widely utilized in temporary stents, though their rapid degradation and susceptibility to bacterial infection pose significant challenges. Our research has developed a nanocomposite coating inspired by the lotus, integrating poly-trimethylene carbonate with covalent organic frameworks (COF). The coating achieved self-polishing property and optimal surface energy on the Mg substrate, which decelerates stent degradation and reduces biofilm formation. Comprehensive evaluations utilizing dynamic bile simulations and implantation in New Zealand rabbit choledochal models reveal that the coating improves the durability and longevity of the stent. The implications of these findings suggest the potential COF-based Mg alloy stent surface treatments and a leap forward in advancing stent performance and endurance in clinical applications.

Covalent Organic Framework-Based Nanomotor for Multimodal Cancer Photo-Theranostics.

Developing efficient integrated diagnosis and treatment agents based on fuel-free self-movement nanomotors remains challenging in antitumor therapy. In this study, a covalent organic framework (COF)-based biomimetic nanomotor composed of polypyrrole (PPy) core, porphyrin-COF shell, and HCT116 cancer cell membrane coating is reported. Under near-infrared (NIR) light irradiation, the obtained mPPy@COF-Por can overcome Brownian motion and achieves directional motion through self-thermophoretic force generated from the PPy core. The HCT116 cancer cell membrane coating enables the nanomotor to selectively recognize the source cell lines and reduces the bio-adhesion of mPPy@COF-Por in a biological medium, endowing with this NIR light-powered nanomotor good mobility. More importantly, such multifunctional integration allows the COF-based nanomotor to be a powerful nanoagent for cancer treatment, and the high infrared thermal imaging/photoacoustic imaging/fluorescence trimodal imaging-guided combined photothermal/photodynamic therapeutic effect on HCT116 tumor cell is successfully achieved. The results offer considerable promise for the development of COF nanomotors with integrated imaging/therapy modalities in biomedical applications.

Minimally invasive maxillary sinus augmentation with simultaneous implantation on an elderly patient: A case report.

BACKGROUND: In this case study, a minimally invasive transalveolar approach using platelet-rich fibrin and bone substitute with simultaneous implantation was carried out in an elderly patient. We analyzed the cone-beam computed tomography (CBCT) findings to evaluate bone regeneration. CASE SUMMARY: A 65-year-old female with no contraindications for dental implants and loss of maxillary bilateral molars is described. Examination by CBCT showed the available vertical bone height in the bilateral posterior maxilla was 0.5-6.8 mm in the left and 2.8-6.5 mm in the right. The patient underwent a transalveolar approach using platelet-rich fibrin and bone substitute with simulataneous placement of an implant 10 mm in length. Six months post-surgery, the implant showed excellent osseointegration with the bone graft. Thereafter, full-ceramic crowns were fitted. Follow-up at 2 years demonstrated satisfactory prognosis. CONCLUSION: Platelet-rich fibrin and bone substitute can be used to augment the maxillary sinus with a vertical bone height less than 4 mm.

Low field nuclear magnetic sensing technology based on hydrogel-coated superparamagnetic particles.

Based on superparamagnetic nanoparticles, a responsive polyacrylamide hydrogel self-assembled by nucleic acid hairpin hybridization chain reaction was designed, and a universal low field nuclear magnetic resonance sensing platform was successfully constructed. As the target was gradually added, the hydrogel coating on the surface of the magnetic nanoparticle was opened layer by layer through binding with the aptamer, which specifically bonded thereto, causing different degrees of exposure of the magnetic nanoparticle, resulting in changes of low field nuclear magnetic resonance signals. This method was originally applied to the rapid detection of adenosine triphosphate (ATP), and the versatility of the method was verified using polychlorinated biphenyl 77 (PCB77). This method had the advantage of being fast, convenient, and low cost, and it can be easily operated with high repeatability. This universal method can detect a variety of targets by replacing aptamers and may be useful in controlling food quality and for rapidly detecting cancer cells in vitro.

In vitro large-scale cultivation and evaluation of microencapsulated immortalized human hepatocytes (HepLL) in roller bottles.

BACKGROUND/AIMS: Microencapsulated hepatocytes have been proposed as promising bioactive agents for packed-bed or fluidized-bed bioartificial liver assist devices (BLaDs) and for hepatocyte transplantation because of the potential advantages they offer of high mass transport rate and an optimal microenvironment for hepatocyte culture. We developed a large-scale and high-production alginate-chitosan (AC) microcapsule roller bottle culture system for the encapsulation of hepLL immortalized human hepatocytes. In this study, the efficacy of upscaling encapsulated hepLL cells production with roller bottle cultivation was evaluated in vitro. METHODS: Microencapsulated hepLL cells were grown at high yield in large-scale roller bottles, with free cells cultured in roller bottle spinners serving as controls. The mechanical stability and the permeability of the AC microcapsules were investigated, and the growth, metabolism and functions of the encapsulated hepLL cells were evaluated as compared to free cells. RESULTS: The microcapsules withstood well the shear stress induced by high agitation rates. The microcapsules were permeable to albumin, but prevented the release of immunoglobulins. Culture in roller bottles of immortalized human hepatocytes immobilized in the AC microcapsules improved cell growth, albumin synthesis, ammonia elimination and lidocaine clearance as compared with free cells cultured in roller bottles. CONCLUSIONS: Encapsulated hepLL cells may be cultured on a large scale in roller bottles. This makes them possible candidates for use in cell-based liver assist therapies.

Role of Vitamin D Receptor Gene Polymorphisms on the Susceptibility to Periodontitis: A Meta-Analysis of a Controversial Issue.

Background: To assess whether vitamin D receptor (VDR) gene polymorphisms influence the susceptibility to periodontitis. Methods: We retrieved 34 relevant studies, comprising a total of 3848 subjects suffering from periodontitis and 3470 controls for this meta-analysis. The pooled data were analyzed using STATA software. Results: Among all ethnic groups examined, the VDR BsmI polymorphism was associated with periodontitis under the recessive model (odds ratio [OR] = 0.722, 95% confidence interval [CI]: 0.532-0.980, p = 0.037). There was also a link between the VDR FokI polymorphism and periodontitis in the overall population (dominant model: OR = 1.459, 95% CI: 1.050-2.028, p = 0.025 and allelic model: OR = 1.386, 95% CI: 1.026-1.874, p = 0.034) and in Chinese participants (dominant model: OR = 1.813, 95% CI: 1.185-2.774, p = 0.006; allelic model: OR = 1.602, 95% CI: 1.044-2.459, p = 0.031) when stratified by race. The FokI variant was also correlated with aggressive periodontitis (AP) (dominant model: OR = 2.204, 95% CI: 1.148-4.231, p = 0.018; allelic model: OR = 2.017, 95% CI: 1.365-2.980, p = 0.000; and recessive model: OR = 2.903, 95% CI: 1.520-5.542, p = 0.001). We also showed a correlation between the VDR TaqI variant and periodontitis susceptibility in Caucasian populations (dominant model: OR = 0.525, 95% CI: 0.318-0.866, p = 0.012). The results revealed that there was no relationship between the VDR ApaI gene polymorphism and periodontitis. Conclusions: There was a link between the VDR BsmI and FokI gene polymorphisms and periodontitis in the overall population. In addition, the FokI polymorphism was correlated with AP. There was a link between the TaqI polymorphism and periodontitis in the Caucasian population. The VDR Apal variant, however, was not correlated with periodontitis.

Preparation and Imaging Investigation of Dual-targeted C3F8-filled PLGA Nanobubbles as a Novel Ultrasound Contrast Agent for Breast Cancer.

Molecularly-targeted contrast enhanced ultrasound (US) imaging is a promising imaging strategy with large potential for improving diagnostic accuracy of conventional US imaging in breast cancer detection. Therefore, we constructed a novel dual-targeted nanosized US contrast agent (UCA) directed at both vascular endothelial growth factor receptor 2 (VEGFR2) and human epidermal growth factor receptor 2 (HER2) based on perfluoropropane (C3F8)-filled poly(lactic-co-glycolic acid) (PLGA) (NBs) for breast cancer detection. In vitro, single- or dual-targeted PLGA NBs showed high target specificities and better effects of target enhancement in VEGFR2 or HER2-positive cells. In vivo, US imaging signal in the murine breast cancer model was significantly higher (P < 0.01) for dual-targeted NBs than single-targeted and non-targeted NBs. Small animal fluorescence imaging further confirmed the special affinity of the dual-targeted nanosized contrast agent to both VEGFR2 and HER2. Immunofluorescence and immunohistochemistry staining confirmed the expressions of VEGFR2 and HER2 on tumor neovasculature and tumor cells of breast cancer. In conclusions, the feasibility of using dual-targeted PLGA NBs to enhance ultrasonic images is demonstrated in vitro and in vivo. This may be a promising approach to target biomarkers of breast cancer for two site-specific US molecular imaging.

Novel double-layer Silastic testicular prosthesis with controlled release of testosterone in vitro, and its effects on castrated rats.

Testicular prostheses have been used to deal with anorchia for nearly 80 years. Here, we evaluated a novel testicular prosthesis that can controllably release hormones to maintain physiological levels of testosterone in vivo for a long time. Silastic testicular prostheses with controlled release of testosterone (STPT) with different dosages of testosterone undecanoate (TU) were prepared and implanted into castrated Sprague-Dawley rats. TU oil was applied by oral administration to a separate group of castrated rats. Castrated untreated and sham-operated groups were used as controls. Serum samples from every group were collected to measure the levels of testosterone (T), follicle-stimulating hormone and luteinizing hormone (LH). Maximum intracavernous penile pressure (ICPmax) was recorded. The prostates and seminal vesicles were weighed and subjected to histology, and a terminal dexynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) assay was used to evaluate apoptosis. Our results revealed that the weights of these tissues and the levels of T and LH showed significant statistical differences in the oral administration and TU replacement groups compared with the castrated group (P < 0.05). Compared with the sham-operated group, the ICPmax, histology and TUNEL staining for apoptosis, showed no significant differences in the hormone replacement groups implanted with medium and high doses of STPT. Our results suggested that this new STPT could release TU stably through its double semi-permeable membranes with excellent biocompatibility. The study provides a new approach for testosterone replacement therapy.