Navigation-based endoscopic enucleation (NBEE) of large mandibular cystic lesions involving the ramus.

OBJECTIVE: The aim of this study was to present an innovative surgical protocol, navigation-based endoscopic enucleation (NBEE) for the treatment of large mandibular cystic lesions involving the mandibular ramus. METHODS: Twelve patients who presented with a large mandibular cystic lesion involving the mandibular ramus were enrolled in this study. Preoperative planning and intraoperative navigation were performed in all 12 patients. RESULTS: All patients in this study were treated with navigation-based endoscopic enucleation successfully. The follow-up period ranged from 7 to 10 months. Bone regenerated was found in all patients postoperatively. Three patients experienced temporary mandibular nerve palsy, and all relieved within 2 months. No pathological bone fracture was found during surgery. CONCLUSIONS: The use of navigation-based endoscopic enucleation (NBEE) for the treatment of large mandibular cystic lesions involving the ramus proved to be an effective method for complete and precise enucleation of the cystic lesion that also preserved the surrounding tissue.

The cleft palate candidate gene BAG6 supports FoxO1 acetylation to promote FasL-mediated apoptosis during palate fusion.

BACKGROUND: Cleft palate is a common craniofacial defect, which occurs when the palate fails to fuse during development. During fusion, the palatal shelves migrate towards the embryonic midline to form a seam. Apoptotic elimination of medial edge epithelium (MEE) cells along this seam is required for the completion of palate fusion. METHODS: Whole exome sequencing (WES) of six Chinese cleft palate families was applied to identify novel cleft palate-associated gene variants. Palatal fusion and immunofluorescence studies were performed in a murine palatal shelf organ culture model. Gene and protein expression were analyzed by qPCR and immunoblotting in murine MEE cells during seam formation in vivo. Mechanistic immunoprecipitation studies were performed in murine MEE cells in vitro. RESULTS: WES identified Bcl-2 associated anthanogene 6 (BAG6) as a novel cleft palate-associated gene. In murine MEE cells, we discovered upregulation of Bag6 and the transcription factor forkhead box protein O1 (FoxO1) during seam formation in vivo. Using a palatal shelf organ culture model, we demonstrate that nuclear-localized Bag6 enhances MEE cell apoptosis by promoting p300's acetylation of FoxO1, thereby promoting transcription of the pro-apoptotic Fas ligand (FasL). Subsequent gain- and loss-of-function studies in the organ culture model demonstrated that FasL is required for Bag6/acFoxO1-mediated activation of pro-apoptotic Bax/caspase-3 signaling, MEE apoptosis, and palate fusion. Palatal shelf contact was shown to enhance Bag6 nuclear localization and upregulate nuclear acFoxO1 in MEE cells. CONCLUSIONS: These findings demonstrate that nuclear-localized Bag6 and p300 co-operatively enhance FoxO1 acetylation to promote FasL-mediated MEE apoptosis during palate fusion.

Increased cellular uptake of peptide-modified PEGylated gold nanoparticles.

Gold nanoparticles are promising drug delivery vehicles for nucleic acids, small molecules, and proteins, allowing various modifications on the particle surface. However, the instability and low bioavailability of gold nanoparticles compromise their clinical application. Here, we functionalized gold nanoparticles with CPP fragments (CALNNPFVYLI, CALRRRRRRRR) through sulfhydryl PEG to increase their stability and bioavailability. The resulting gold nanoparticles were characterized with transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-visible spectrometry and X-ray photoelectron spectroscopy (XPS), and the stability in biological solutions was evaluated. Comparing to PEGylated gold nanoparticles, CPP (CALNNPFVYLI, CALRRRRRRRR)-modified gold nanoparticles showed 46 folds increase in cellular uptake in A549 and B16 cell lines, as evidenced by the inductively coupled plasma atomic emission spectroscopy (ICP-AES). The interactions between gold nanoparticles and liposomes indicated CPP-modified gold nanoparticles bind to cell membrane more effectively than PEGylated gold nanoparticles. Surface plasmon resonance (SPR) was used to measure interactions between nanoparticles and the membrane. TEM and uptake inhibitor experiments indicated that the cellular entry of gold nanoparticles was mediated by clathrin and macropinocytosis. Other energy independent endocytosis pathways were also identified. Our work revealed a new strategy to modify gold nanoparticles with CPP and illustrated the cellular uptake pathway of CPP-modified gold nanoparticles.

Molecular Mechanisms of Ultrafiltration Membrane Fouling in Polymer-Flooding Wastewater Treatment: Role of Ions in Polymeric Fouling.

Polymer (i.e., anionic polyacrylamide (APAM)) fouling of polyvinylidene fluoride (PVDF) ultrafiltration (UF) membranes and its relationships to intermolecular interactions were investigated using atomic force microscopy (AFM). Distinct relations were obtained between the AFM force spectroscopy measurements and calculated fouling resistance over the concentration polarization layer (CPL) and gel layer (GL). The measured maximum adhesion forces (Fad,max) were closely correlated with the CPL resistance (Rp), and the proposed molecular packing property (largely based on the shape of AFM force spectroscopy curve) of the APAM chains was related to the GL resistance (Rg). Calcium ions (Ca(2+)) and sodium ions (Na(+)) caused more severe fouling. In the presence of Ca(2+), the large Rp corresponded to high foulant-foulant Fad,max, resulting in high flux loss. In addition, the Rg with Ca(2+) was minor, but the flux recovery rate after chemical cleaning was the lowest, indicating that Ca(2+) created more challenges in GL cleaning. With Na(+), the fouling behavior was complicated and concentration-dependent. The GL structures with Na(+), which might correspond to the proposed molecular packing states among APAM chains, played essential roles in membrane fouling and GL cleaning.

Silver Mineralized Protein Hydrogel with Intrinsic Cell Proliferation Promotion and Broad-Spectrum Antimicrobial Properties for Accelerated Infected Wound Healing.

The presence of multidrug-resistant bacteria has challenged the clinical treatment of bacterial infection. There is a real need for the development of novel biocompatible materials with broad-spectrum antimicrobial activities. Antimicrobial hydrogels show great potential in infected wound healing but are still being challenged. Herein, broad-spectrum antibacterial and mechanically tunable amyloid-based hydrogels based on self-assembly and local mineralization of silver nanoparticles are reported. The mineralized hydrogels are biocompatible and have the advantages of sustained release of silver, prolonged antimicrobial effect, and improved adhesion capacity. Moreover, the mineralized hydrogels display a significant antimicrobial effect against both Gram-positive and Gram-negative bacteria in cells and mice by inducing membrane damage and reactive oxygen species toxicity in bacteria. In addition, the mineralized hydrogels can rapidly accelerate wound healing by the synergy between their antibacterial activity and intrinsic improvement for cell proliferation and migration. This study provides a modular approach to developing a multifunctional protein hydrogel platform based on biomolecule-coordinated self-assembly for a wide range of biomedical applications.

Oxidative stress and gene expression induced by biodegradable microplastics and imidacloprid in earthworms (Eisenia fetida) at environmentally relevant concentrations.

The environmental issues caused by biodegradable microplastics (BMPs) from polylactic acid (PLA) as well as pesticides are of increasing concern nowadays. In this study, the toxicological effects of the single and combined exposure of PLA BMPs and imidacloprid (IMI), a neonicotinoid insecticide, on earthworms (Eisenia fetida) were investigated in terms of oxidative stress, DNA damage, and gene expression, respectively. The results showed that compared with the control, SOD, CAT and AChE activities in the single and combined treatments decreased significantly, and POD activity showed an "inhibition-activation" trend. SOD and CAT activities of combined treatments on day 28 and AChE activity of combined treatment on day 21 were significantly higher than those of the single treatments. For the rest of the exposure period, SOD, CAT and AChE activities in the combined treatments were lower than those in the single treatments. POD activity in the combined treatment was significantly lower than those of single treatments at day 7 and higher than that of single treatments at day 28. MDA content showed an "inhibition-activation-inhibition" trend, and the ROS level and 8-OHdG content increased significantly in both the single and combined treatments. This shows that both single and combined treatments led to oxidative stress and DNA damage. ANN and HSP70 were expressed abnormally, while the SOD and CAT mRNA expression changes were generally consistent with the corresponding enzyme activities. The integrated biomarker response (IBR) values were higher under combined exposures than single exposures at both biochemical and molecular levels, indicating that combined treatment exacerbated the toxicity. However, the IBR value of the combined treatment decreased consistently at the time axis. Overall, our results suggest that PLA BMPs and IMI induce oxidative stress and gene expression in earthworms at environmentally relevant concentrations, thereby increasing the risk of earthworms.

Interactive effects of cerium and copper to tune the microstructure of silicocarnotite bioceramics towards enhanced bioactivity and good biosafety.

Endowing biomaterials with functional elements enhances their biological properties effectively. However, improving bioactivity and biosafety simultaneously is still highly desirable. Herein, cerium (Ce) and copper (Cu) are incorporated into silicocarnotite (CPS) to modulate the constitution and microstructure for degradability, bioactivity and biosafety regulation. Our results demonstrated that introducing Ce suppressed scaffold degradation, while, co-incorporation of both Ce and Cu accelerated degradability. Osteogenic effect of CPS in vitro was promoted by Ce and optimized by Cu, and Ce-induced angiogenic inhibition could be mitigated by cell coculture method and reversed by Ce-Cu co-incorporation. Ce enhanced osteogenic and angiogenic properties of CPS in a dose-dependent manner in vivo, and Cu-Ce coexistence exhibited optimal bioactivity and satisfactory biosafety. This work demonstrated that coculture in vitro was more appropriately reflecting the behavior of implanted biomaterials in vivo. Interactive effects of multi-metal elements were promising to enhance bioactivity and biosafety concurrently. The present work provided a promising biomaterial for bone repair and regeneration, and offered a comprehensive strategy to design new biomaterials which aimed at adjustable degradation behavior, and enhanced bioactivity and biosafety.

Radiological features of central giant cell granuloma: comparative study of 7 cases and literature review.

OBJECTIVE: To review and analyze the clinical and imaging features of central giant cell granuloma patients and to review the relevant literatures for the diagnosis and clinical manifestation of central giant cell granuloma. METHODS: Seven cases of central giant cell granuloma were retrospectively selected for the study, all of which were confirmed by pathology and had relevant imaging investigations. All seven cases had undergone CT scan, three cases had undergone MRI scan. Detailed clinical features were compared along with the imaging findings and analysis was done on the basis of their presentation and imaging features. RESULTS: The clinical features, radiologic features were varied according to the site of the lesion. CT features include unevenly dense expansile mass causing bone destruction and cortical thinning. While MRI features with low to iso-intensity in T1- and T2 weighted images. There may be presence of cystic degeneration, hemorrhage or hemosiderin deposits or osteoid formation, which can cause T1 and T2 signal changes. On contrast study, the lesion doesn't enhance but periphery may enhance mildly. CONCLUSION: Unevenly dense expansile mass with bone destruction and cortical thinning with low to iso-intensity in T1 weighted and T2 weighted images and mildly enhance peripherally, Central giant cell granuloma should be considered.

A novel bifunctional glucanase exhibiting high production of glucose and cellobiose from rumen bacterium.

Herbivores gastrointestinal microbiota is of tremendous interest for mining novel lignocellulosic enzymes for bioprocessing. We previously reported a set of potential carbohydrate-active enzymes from the metatranscriptome of the Hu sheep rumen microbiome. In this study, we isolated and heterologously expressed two novel glucanase genes, Cel5A-h38 and Cel5A-h49, finding that both recombinant enzymes showed the optimum temperatures of 50 °C. Substrate-specificity determination revealed that Cel5A-h38 was exclusively active in the presence of mixed-linked glucans, such as barley ß-glucan and Icelandic moss lichenan, whereas Cel5A-h49 (EC 3.2.1.4) exhibited a wider substrate spectrum. Surprisingly, Cel5A-h38 initially released only cellotriose from lichenan and further converted it into an equivalent amount of glucose and cellobiose, suggesting a dual-function as both endo-ß-1,3-1,4-glucanase (EC 3.2.1.73) and exo-cellobiohydrolase (EC 3.2.1.91). Additionally, we performed enzymatic hydrolysis of sheepgrass (Leymus chinensis) and rice (Orysa sativa) straw using Cel5A-h38, revealing liberation of 1.91 ± 0.30 mmol/mL and 2.03 ± 0.09 mmol/mL reducing sugars, respectively, including high concentrations of glucose and cellobiose. These results provided new insights into glucanase activity and lay a foundation for bioconversion of lignocellulosic biomass.

Cisplatin and oxaliplatin inhibit gap junctional communication by direct action and by reduction of connexin expression, thereby counteracting cytotoxic efficacy.

Cisplatin [cis-diamminedichloroplatinum(II)]/oxaliplatin [1,2-diamminocyclohexane(trans-1)oxolatoplatinum(II)] toxicity is enhanced by functional gap junctions between treated cells, implying that inhibition of gap junctions may decrease cytotoxic activity of these platinum-based agents. This study investigates the effect of gap junction modulation by cisplatin/oxaliplatin on cytotoxicity in a transformed cell line. The effects were explored using junctional channels expressed in transfected HeLa cells and purified hemichannels. Junctional channels showed a rapid, dose-dependent decrease in dye coupling with exposure to cisplatin/oxaliplatin. With longer exposure, both compounds also decreased connexin expression. Both compounds inhibit the activity of purified connexin hemichannels, over the same concentration range that they inhibit junctional dye permeability, demonstrating that inhibition occurs by direct interaction of the drugs with connexin protein. Cisplatin/oxaliplatin reduced the clonogenic survival of HeLa cells at low density and high density in a dose-dependent manner, but to a greater degree at high density, consistent with a positive effect of gap junctional intercellular communication (GJIC) on cytotoxicity. Reduction of GJIC by genetic or pharmacological means decreased cisplatin/oxaliplatin toxicity. At low cisplatin/oxaliplatin concentrations, where effects on connexin channels are minimal, the toxicity increased with increased cell density. However, higher concentrations strongly inhibited GJIC, and this counteracted the enhancing effect of greater cell density on toxicity. The present results indicate that inhibition of GJIC by cisplatin/oxaliplatin decreases their cytotoxicity. Direct inhibition of GJIC and reduction of connexin expression by cisplatin/oxaliplatin may thereby compromise the effectiveness of these compounds and be a factor in the development of resistance to this class of chemotherapeutic agents.

Syndiotactic polystyrene nanofibrils in silica nanotube reactors: understanding of synthesis with ultrahigh molecular weight.

Nanofibrils of ultrahigh molecular weight syndiotactic polystyrene (sPS) have been synthesized in a silica nanotube reactor (SNTR) using a metallocene catalyst in conjunction with methylaluminoxane cocatalyst. Very thin sPS nanofibrils (<10 nm) grown at the catalytic sites on the pore walls aggregate to form intertwined, rope-like nanofibrils with 30-50 nm diameters, which further intertwine into even larger 200 nm diameter polymer nanofibrils. The extrusion of nanofibrils synthesized inside the SNTR was directly observed by scanning electron microscopy, and the individual SNTR containing a single polymer nanofibril was separated and observed by transmission electron microscopy. The sPS synthesized in the SNTR has ultrahigh molecular weight (Mw = 928,000 g/mol) with a large fraction of 2 000,000-5,000,000 g/mol molecular weight polymers.

Evaluation of stiffness feedback for hard nodule identification on a phantom silicone model.

Haptic information in robotic surgery can significantly improve clinical outcomes and help detect hard soft-tissue inclusions that indicate potential abnormalities. Visual representation of tissue stiffness information is a cost-effective technique. Meanwhile, direct force feedback, although considerably more expensive than visual representation, is an intuitive method of conveying information regarding tissue stiffness to surgeons. In this study, real-time visual stiffness feedback by sliding indentation palpation is proposed, validated, and compared with force feedback involving human subjects. In an experimental tele-manipulation environment, a dynamically updated color map depicting the stiffness of probed soft tissue is presented via a graphical interface. The force feedback is provided, aided by a master haptic device. The haptic device uses data acquired from an F/T sensor attached to the end-effector of a tele-manipulated robot. Hard nodule detection performance is evaluated for 2 modes (force feedback and visual stiffness feedback) of stiffness feedback on an artificial organ containing buried stiff nodules. From this artificial organ, a virtual-environment tissue model is generated based on sliding indentation measurements. Employing this virtual-environment tissue model, we compare the performance of human participants in distinguishing differently sized hard nodules by force feedback and visual stiffness feedback. Results indicate that the proposed distributed visual representation of tissue stiffness can be used effectively for hard nodule identification. The representation can also be used as a sufficient substitute for force feedback in tissue palpation.

A highly sensitive and selective sensor based on a graphene-coated carbon paste electrode modified with a computationally designed boron-embedded duplex molecularly imprinted hybrid membrane for the sensing of lamotrigine.

An innovative electrochemical sensor, based on a carbon paste electrode (CPE) modified with graphene (GR) and a boron-embedded duplex molecularly imprinted hybrid membrane (B-DMIHM), was fabricated for the highly sensitive and selective determination of lamotrigine (LMT). Density functional theory (DFT) was employed to study the interactions between the template and monomers to screen appropriate functional monomers for rational design of the B-DMIHM. The distinct synergic effect of GR and B-DMIHM was evidenced by the positive shift of the reduction peak potential of LMT at B-DMIHM/GR modified CPE (B-DMIHM/GR/CPE) by about 300mV, and the 13-fold amplification of the peak current, compared to a bare carbon paste electrode (CPE). The electrochemical reduction mechanism of lamotrigine was investigated by different voltammetric techniques. It was illustrated that square wave voltammetry (SWV) was more sensitive than different pulse voltammetry (DPV) for the quantitative analysis of LMT. Thereafter, a highly sensitive electroanalytical method for LMT was established by SWV at B-DMIHM/GR/CPE with a good linear relationship from 5.0×10-8 to 5.0×10-5 and 5.0×10-5 to 3.0×10-4molL-1 with a lower detection limit (1.52×10-9molL-1) based on the lower linear range(S/N=3). The practical application of the sensor was demonstrated by determining the concentration of LMT in pharmaceutical and biological samples with good precision (RSD 1.04-4.41%) and acceptable recoveries (92.40-107.0%).

Comprehensively priming the tumor microenvironment by cancer-associated fibroblast-targeted liposomes for combined therapy with cancer cell-targeted chemotherapeutic drug delivery system.

Cancer-associated fibroblasts (CAFs) not only support tumorigenesis and tumor metastasis by reciprocal cellular cross-talk with cancer cells, but also remodel the extracellular matrix (ECM) and architecture of tumor microenvironment. This leads to poor tumor penetration of traditional chemotherapeutic nanomedicines and resulting drug resistance. In this study, we use a novel tumor stroma-targeted nanovehicle (FH-SSL-Nav) to specifically eradicate CAFs, promote tumor penetration of nanomedicines and cut off the stroma's support to cancer cells. FH-SSL-Nav exhibited excellent and comprehensive tumor microenvironment modulation including downregulation ECM deposition, decreasing interstitial fluid pressure (IFP) and facilitating blood perfusion. As a result, more chemotherapeutic drug delivery systems penetrated deep into tumor spheroids in vitro and tumor tissues in vivo. Furthermore, chemotherapeutic drug resistance induced by microenvironment was partly reversed by FH-SSL-Nav. In a human Hep G2 xenograft nude mouse model, FH-SSL-Nav greatly improved the tumor suppression of cancer cell-targeted liposomal doxorubicin (7pep-SSL-DOX) with low dose and low toxicity. Since Nav and DOX exhibited no synergy against Hep G2 cells, it was clear that the improved antitumor efficacy was basically due to the comprehensive tumor microenvironment priming by FH-SSL-Nav.

Synthesis of direct white-light emitting carbogenic quantum dots.

A facile chemical method has been developed to synthesise highly efficient functionalized carbon dots; when illuminated with 407 nm light, both the solution and film emitted white-light directly.