Dual Engine Boosts Organic Photoelectrochemical Transistor for Enhanced Modulation and Bioanalysis.

Organic photoelectrochemical transistor (OPECT) has shown substantial potential in the development of next-generation bioanalysis yet is limited by the either-or situation between the photoelectrode types and the channel types. Inspired by the dual-photoelectrode systems, we propose a new architecture of dual-engine OPECT for enhanced signal modulation and its biosensing application. Exemplified by incorporating the CdS/Bi2S3 photoanode and Cu2O photocathode within the gate-source circuit of Ag/AgCl-gated poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) channel, the device shows enhanced modulation capability and larger transconductance (gm) against the single-photoelectrode ones. Moreover, the light irritation upon the device effectively shifts the peak value of gm to zero gate voltage without degradation and generates larger current steps that are advantageous for the sensitive bioanalysis. Based on the as-developed dual-photoelectrode OPECT, target-mediated recycling and etching reactions are designed upon the CdS/Bi2S3, which could result in dual signal amplification and realize the sensitive microRNA-155 biodetection with a linear range from 1 fM to 100 pM and a lower detection limit of 0.12 fM.

Treatment outcomes of regenerative endodontic procedures in nonvital mature permanent teeth: a retrospective study.

OBJECTIVES: This retrospective study was undertaken to clinically and radiographically evaluate the long-term outcomes of regenerative endodontic procedures (REPs) for nonvital mature permanent teeth, to analyze predictors influencing treatment outcomes. METHODS: Nonvital mature permanent teeth treated by REPs with a minimum follow-up period of 6 months were included from 2015 to 2017. Treatment outcomes were categorized as success and failure. The periapical status and lesion healing were assessed in terms of the periapical index (PAI) and the percentage changes in periapical radiolucency (PARL) area. The clinical and radiographic outcomes of REPs were assessed by Mann-Whitney test at different follow-up period. Kaplan-Meier curves and Univariate Cox regression analysis were conducted to assess the success and identify potential predictors affecting outcomes, respectively. RESULTS: A total of 37 mature teeth with an average follow-up of 4.3 years satisfied the criteria, and 89.2% of the teeth had a successful outcome. Significant differences in PAI scores were found between each period with respect to the baseline (p < .05). Among different periods, there was a significant difference between intervals of 3-6 months and 7-12 months (p = .039) and no significant difference between each interval of more than 12 months (p > .05). Eighty-seven percent of teeth with preoperative PARL presented completely healed. REPs significantly decreased the PARL area at the interval of 7-12 months compared to 3-6 months (p = .025), with no significant difference between each interval of more than 12 months (p > .05). No significant predictor was found for the success of outcome (p > .05). Thirteen teeth (35.1%) regained pulp sensibility, and 40.5% of the teeth exhibited intracanal calcification. CONCLUSIONS: Within the limitations of this study, REPs provided a high long-term success rate and promoted the resolution of PARL as a biologically-based alternative treatment option for nonvital mature teeth. CLINICAL RELEVANCE: REPs provide a high long-term success rate and promoted healing of apical periodontitis comparable with reported outcomes for root canal therapy of mature teeth.

Polymer Dot-Gated Accumulation-Type Organic Photoelectrochemical Transistor for Urea Biosensing.

Organic photoelectrochemical transistor (OPECT) biosensing represents a new platform interfacing optoelectronics and biological systems with essential amplification, which, nevertheless, are concentrated on depletion-type operation to date. Here, a polymer dot (Pdot)-gated accumulation-type OPECT biosensor is devised and applied for sensitive urea detection. In such a device, the as-designed Pdot/poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine] (PTAA) is validated as a superior gating module against the diethylenetriamine (DETA) de-doped poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) channel, and the urea-dependent status of Pdots has been shown to be sensitively correlated with the device's response. High-performance urea detection is thus realized with a wide linear range of 1 µM-50 mM and a low detection limit of 195 nM. Given the diversity of the Pdot family and its immense interactions with other species, this work represents a generic platform for developing advanced accumulation-type OPECT and beyond.

A Shear-Thinning Biomaterial-Mediated Immune Checkpoint Blockade.

Systemic administration of immune checkpoint blockade agents can activate the anticancer activity of immune cells; however, the response varies from patient to patient and presents potential off-target toxicities. Local administration of immune checkpoint inhibitors (ICIs) can maximize therapeutic efficacies while reducing side effects. This study demonstrates a minimally invasive strategy to locally deliver anti-programmed cell death protein 1 (anti-PD-1) with shear-thinning biomaterials (STBs). ICI can be injected into tumors when loaded in STBs (STB-ICI) composed of gelatin and silicate nanoplatelets (Laponite). The release of ICI from STB was mainly affected by the Laponite percentage in STBs and pH of the local microenvironment. Low Laponite content and acidic pH can induce ICI release. In a murine melanoma model, the injection of STB-ICI significantly reduced tumor growth and increased CD8+ T cell level in peripheral blood. STB-ICI also induced increased levels of tumor-infiltrating CD4+ helper T cells, CD8+ cytotoxic T cells, and tumor death. The STB-based minimally invasive strategy provides a simple and efficient approach to deliver ICIs locally.

[Endoscopic anatomy involving the extended transsphenoidal approach].

OBJECTIVE: To provide pertinent anatomic data and details for the clinical application of the extended transsphenoidal approach; to probe the anatomic characteristic and method under endoscope; METHODS: 25 adult cadaver heads fixed in formalin were used to dissect, observe, measure and photograph the relationship between the neural and vascular structure and the important anatomic landmarks related to the extended transsphenoidal approach under endoscope. RESULTS: The posterior and lateral wall of sphenoidal sinus could be well exposed by bilateral approach under endoscope. The clinical application of endoscope could improve the illumination of the operative field, magnify the objects and provide two-dimensional images. The distortion of the images under endoscope depended upon the distance between the lens and the object as well as the angle of the lens. To establish the anatomic vertical compartment under the endoscope might be helpful to the operation. The midline vertical compartment consisted of the planum sphenoidale, tuberculum sella, sella and clival indentation. The paramedian vertical compartment was composed of the medial third of the optic canal and the carotid artery protuberance. The lateral vertical compartment contained four bony protuberances (optic, cavernous sinus apex, maxillary, and mandibular). Endoscopic surgical maneuvering was under non-midline direction. Precise surgical landmarks are essential for a successful operation. These landmarks allowed the surgeon to recognize and approach the surgical target without confusion. The nasopharynx, middle turbinate, and inferior turbinate were some of the landmarks in the nasal cavity. Once the sphenoidal sinus was entered, the anatomic structures of the sphenoidal sinus posterior wall, which were described above, were the unique landmarks that will guide the surgeon to the surgical target. CONCLUSION: The anatomic characteristics under endoscope were different from those under microscope. The application of the extended transsphenoidal approach under endoscope could provide more extensive vision and satisfied exposure to reach the area of the central skull base.

Biomechanical evaluation of vertebroplasty using calcium sulfate cement for thoracolumbar burst fractures.

OBJECTIVE: To evaluate the biomechanical performance of vertebroplasty using calcium sulfate cement for thoracolumbar burst fractures. METHODS: Sixteen bovine thoracolumbar spines (T11-L1) were divided into 4 groups (A,B,C and D). After burst-fracture model was created, 12 vertebral bodies in Groups A, B and C were augmented with calcium sulfate cement (CSC), calcium phosphate cement (CPC) and polymethylmethacrylate (PMMA) bone cement, respectively. Each anterior vertebral body height was measured with a caliper at 4 time points: intact conditions (HInt), post-fracture (HFr), post-reduction (HRe) and post-vertebroplasty (HVP). The filling volume of 3 different bone cements was also measured. Each vertebral body was compressed at 0.5 mm/s using a hinged plating system on a materials testing machine to 50% of the post-vertebroplasty height to determine strength and stiffness. Difference was checked using t test or One-way ANOVA. RESULTS: The average strike energy was 66.2 J. Vertebroplasty with different cements could sustain vertebral height. The average filling volume of bone cement in 3 groups was 4.35 ml (CSC), 3.72 ml (CPC) and 3.95 ml (PMMA), respectively, and there was no statistically significant difference among them (P larger than 0.05). Vertebroplasty with PMMA completely restored strength (116%) and stiffness (105%). CSC or CPC partly recovered vertebral strength and stiffness. However, greater strength restoration was got with CSC (1659 N) as compared with CPC (1011N, P less than 0.01). Regarding stiffness, differences between CSC (140 N/mm+/-40 N/mm)and the other two bone cements (CPC:148 N/mm+/-33 N/mm, PMMA:236 N/mm+/-97 N/mm) were not significant (P larger than 0.05). CONCLUSIONS: For a burst-fracture of calf spine, use of CSC for vertebroplasty yields similar vertebral stiffness as compared with PMMA or CPC. Although augmentation with CSC partly obtains the normal strength, this treatment still can be applied in thoracolumbar burst fractures with other instrumental devices in light of its bioactivation.

Enhancement of radiotherapy efficacy by pleiotropic liposomes encapsulated paclitaxel and perfluorotributylamine.

Paclitaxel (PTX) is widely used as a radiosensitizer in the clinical treatment of cancer. However, the efficacy of chemoradiotherapy is limited by the hostility of the tumor microenvironment such as hypoxia. To overcome this constraint, we designed pleiotropic radiotherapy sensitized liposomes containing perfluorotributylamine (PFTBA) and PTX. The results showed that liposomes significantly accumulated in the tumor site. PFTBA in liposomes dramatically reversed tumor hypoxia and improved the sensitivity of tumor radiotherapy. PTX in liposomes blocked the cell cycle of tumor cells in the radiation-sensitive G2/M phase, which was even greater when combined with PFTBA. In vitro and in vivo tumor treatment further demonstrated remarkably improved therapeutic outcomes in radiotherapy with such biocompatible liposomes. In conclusion, the pleiotropic liposomes encapsulated PFTBA and PTX provide significant radiotherapy sensitization and show promise for future application in clinical medicine.

Monoclonal antibodies for diagnosis of enterovirus 71.

Enterovirus 71 (EV71), one of the major causative agents of hand, foot, and mouth disease (HFMD), is now recognized as an emerging neurotropic virus in Asia and may cause severe neurologic complications and mortalities. Laboratory diagnosis of EV71 infection must be efficient and accurate, which could be accomplished by various immunoassays. In this study we use a live EV71 isolate, Tainan/4643/98, with genotype C2 as an immunogen to sensitize BALB/c (H-2(d)) mice and then generate the EV71-specific murine monoclonal antibodies. Five hybridoma clones were established and their monoclonal antibodies were characterized. All five clones are applicable in immunofluorescence staining but with different sensitivities-that is, MAbs 22, 24, and 27 were sensitive in IFA detection, and MAbs 22 and 24 were also confirmed in flow cytometry. None of these cross-reacted with coxsackievirus A16 (CVA16) or Echovirus type 6 (ECHO6), but each varied in binding to different EV71 subgenogroups (B1, B4, B5, C2, and C4). Western blot analysis revealed that all of these MAbs reacted with EV71 VP1 capsid proteins, and in addition MAbs 22 and 24 exhibited potent neutralizing activities against EV71 and protected cells from infection. Further, mapping the epitopes for each MAb revealed that only MAb 27 showed positive for the linear epitope DVIESSIGDSVSRAL, which was located at the N-terminus (a.a. 6-20) of EV71 VP1 and highly conserved among all EV71 subgenotypes. Thus, these MAbs may provide valuable tools for the laboratory diagnosis of EV71 infection and for vaccine development.

Laminin/ß1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization.

Axon specification during neuronal polarization is closely associated with increased microtubule stabilization in one of the neurites of unpolarized neuron, but how this increased microtubule stability is achieved is unclear. Here, we show that extracellular matrix (ECM) component laminin promotes neuronal polarization via regulating directional microtubule assembly through ß1 integrin (Itgb1). Contact with laminin coated on culture substrate or polystyrene beads was sufficient for axon specification of undifferentiated neurites in cultured hippocampal neurons and cortical slices. Active Itgb1 was found to be concentrated in laminin-contacting neurites. Axon formation was promoted and abolished by enhancing and attenuating Itgb1 signaling, respectively. Interestingly, laminin contact promoted plus-end microtubule assembly in a manner that required Itgb1. Moreover, stabilizing microtubules partially prevented polarization defects caused by Itgb1 downregulation. Finally, genetic ablation of Itgb1 in dorsal telencephalic progenitors caused deficits in axon development of cortical pyramidal neurons. Thus, laminin/Itgb1 signaling plays an instructive role in axon initiation and growth, both in vitro and in vivo, through the regulation of microtubule assembly. This study has established a linkage between an extrinsic factor and intrinsic cytoskeletal dynamics during neuronal polarization.

Osteogenic gene expression of canine bone marrow stromal cell and bacterial adhesion on titanium with different nanotubes.

Bacterial infection and osseointegration of implant-biomaterials all play important roles in the success of an orthopedic prosthesis or a dental-implant. In this work, we evaluated the osteogenic gene expression of canine bone marrow stromal cells (CBMSCs) and the adhesion of Staphylococcus aureus (ATCC 12598) on different diameter TiO(2) nanotube layers. The CBMSCs cultured on 30 and 70 nm nanotubes displayed polygon shape, but obviously elongated when the diameter of nanotubes turned to 120 nm. A significant increase in CBMSCs proliferation by as much as about ∼300%, and osteogenic gene (RUNX-2, OPN, COL-1, and OCN) expression were observed on the 120 nm diameter nanotubes when compared to the smooth Ti. However, the adhesion of bacteria also increased with an increased tube diameter and reached highest value on 120 nm nanotubes after 4 h of incubation. ∼300-400% increase in bacterial attached to 120 nm nanotubes in contract to the smooth Ti. These data suggested reducing bacteria colonization should be considered when larger diameter nanotubes with better osteogenic property would be used as orthopedic implants or dental implants.