Reexamining the effects of drug loading on the in vivo performance of PEGylated liposomal doxorubicin.

Higher drug loading employed in nanoscale delivery platforms is a goal that researchers have long sought after. But such viewpoint remains controversial because the impacts that nanocarriers bring about on bodies have been seriously overlooked. In the present study we investigated the effects of drug loading on the in vivo performance of PEGylated liposomal doxorubicin (PLD). We prepared PLDs with two different drug loading rates: high drug loading rate, H-Dox, 12.9% w/w Dox/HSPC; low drug loading rate, L-Dox, 2.4% w/w Dox/HSPC (L-Dox had about 5 folds drug carriers of H-Dox at the same Dox dose). The pharmaceutical properties and biological effects of H-Dox and L-Dox were compared in mice, rats or 4T1 subcutaneous tumor-bearing mice. We showed that the lowering of doxorubicin loading did not cause substantial shifts to the pharmaceutical properties of PLDs such as in vitro and in vivo stability (stable), anti-tumor effect (equivalent effective), as well as tissue and cellular distribution. Moreover, it was even more beneficial for mitigating the undesired biological effects caused by PLDs, through prolonging blood circulation and alleviating cutaneous accumulation in the presence of pre-existing anti-PEG Abs due to less opsonins (e.g. IgM and C3) deposition on per particle. Our results warn that the effects of drug loading would be much more convoluted than expected due to the complex intermediation between nanocarriers and bodies, urging independent investigation for each individual delivery platform to facilitate clinical translation and application.

Inhaled Lipid Nanoparticles Alleviate Established Pulmonary Fibrosis.

Pulmonary fibrosis, a sequela of lung injury resulting from severe infection such as severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) infection, is a kind of life-threatening lung disease with limited therapeutic options. Herein, inhalable liposomes encapsulating metformin, a first-line antidiabetic drug that has been reported to effectively reverse pulmonary fibrosis by modulating multiple metabolic pathways, and nintedanib, a well-known antifibrotic drug that has been widely used in the clinic, are developed for pulmonary fibrosis treatment. The composition of liposomes made of neutral, cationic or anionic lipids, and poly(ethylene glycol) (PEG) is optimized by evaluating their retention in the lung after inhalation. Neutral liposomes with suitable PEG shielding are found to be ideal delivery carriers for metformin and nintedanib with significantly prolonged retention in the lung. Moreover, repeated noninvasive aerosol inhalation delivery of metformin and nintedanib loaded liposomes can effectively diminish the development of fibrosis and improve pulmonary function in bleomycin-induced pulmonary fibrosis by promoting myofibroblast deactivation and apoptosis, inhibiting transforming growth factor 1 (TGFß1) action, suppressing collagen formation, and inducing lipogenic differentiation. Therefore, this work presents a versatile platform with promising clinical translation potential for the noninvasive inhalation delivery of drugs for respiratory disease treatment.

Genome-wide identification and expression analysis of MYB gene family in Cajanus cajan and CcMYB107 improves plant drought tolerance.

MYB transcription factor (TF) is one of the largest superfamilies that play a vital role in multiple plant biological processes. However, the MYB family has not been comprehensively identified and functionally verified in Cajanus cajan, which is the sixth most important legume crop. Here, 170 CcR2R3-MYBs were identified and divided into 43 functional subgroups. Segmental and tandem duplications and alternative splicing events were found and promoted the expansion of the CcR2R3-MYB gene family. Functional prediction results showed that CcR2R3-MYBs were mainly involved in secondary metabolism, cell fate and identity, developmental processes, and responses to abiotic stress. Cis-acting element analysis of promoters revealed that stress response elements were widespread in the above four functional branches, further suggesting CcR2R3-MYBs were extensively involved in abiotic stress response. The transcriptome data and qRT-PCR results indicated that most of the CcR2R3-MYB genes responded to various stresses, of which the expression of CcMYB107 was significantly induced by drought stress. Overexpression of CcMYB107 enhanced antioxidant enzyme activity and increased proline and lignin accumulation, thus improving the drought resistance of C. cajan. Furthermore, Overexpression of CcMYB107 up-regulated the expression of stress-related genes and lignin biosynthesis genes after drought stress. Our findings established a strong foundation for the investigation of biological function of CcR2R3-MYB TFs in C. cajan.

Efficiency evaluation of maxillary molar distalization using Invisalign based on palatal rugae registration.

INTRODUCTION: This study aimed to compare the predicted maxillary molar distalization with the achieved clinical outcome using the palatal rugae area for registration and superimposition of digital models. Understanding Invisalign efficiency may assist clinicians in predicting changes, thus applying specific measures to minimize the chance of midcourse correction later. METHODS: The study sample included 38 patients with a mean age of 25.4 years, eligible for Invisalign treatment and requiring distalization of maxillary molars. Two digital models were acquired using iTero intraoral scanner (Align Technology, Santa Clara, Calif) before treatment and after maxillary first and second molar distalization. The 2 digital models were superimposed using the palatal rugae area for registration. The predicted tooth movement compared to the achieved values. One hundred forty-two maxillary molars (71 first molar and 71 second molar) were measured for distal movement, and 228 maxillary anterior teeth were evaluated for anterior anchorage loss. RESULTS: The predicted distal movement of the maxillary first molar (P <0.0001) and maxillary second molar (P <0.0001) differed significantly from the actual values. There was a statistically significant correlation between the amount of distal molar movement and the amount of anchorage loss (r = 0.3900, P <0.008) for the central incisor, and (r = 0.3595, P <0.013) for the lateral incisor. CONCLUSIONS: Invisalign can be used successfully for adult patients requiring maxillary molar distalization when a mean distalization movement of 2.6 mm was prescribed. Clinicians should be aware of the countereffect if maxillary molars are planned to move distally, especially if the patient presented initially with a large overjet, so the need to prescribe overcorrection or the use of auxiliaries can be addressed earlier.

Age estimation in northern Chinese children by measurement of open apices in tooth roots.

The aim of this study was to assess the accuracy of Cameriere's methods on dental age estimation in the northern Chinese population. A sample of orthopantomographs of 785 healthy children (397 girls and 388 boys) aged between 5 and 15 years was collected. The seven left permanent mandibular teeth were evaluated with Cameriere's method. The sample was split into a training set to develop a Chinese-specific prediction formula and a test set to validate this novel developed formula. Following the training dataset study, the variables gender (g), x 3 (canine teeth), x 4 (first premolar), x 7 (second molar), N 0, and the first-order interaction between s and N 0 contributed significantly to the fit, yielding the following linear regression formula: Age = 10.202 + 0.826 g - 4.068x 3 - 1.536x 4 - 1.959x 7 + 0.536 N 0 - 0.219 s [Symbol: see text] N 0, where g is a variable, 1 for boys and 0 for girls. The equation explained 91.2 % (R (2) = 0.912) of the total deviance. By analyzing the test dataset, the accuracy of the European formula and Chinese formula was determined by the difference between the estimated dental age (DA) and chronological age (CA). The European formula verified on the collected Chinese children underestimated chronological age with a mean difference of around -0.23 year, while the Chinese formula underestimated the chronological age with a mean difference of -0.04 year. Significant differences in mean differences in years (DA - CA) and absolute difference (AD) between the Chinese-specific prediction formula and Cameriere's European formula were observed. In conclusion, a Chinese-specific prediction formula based on a large Chinese reference sample could ameliorate the age prediction accuracy in the age group of children.

The influence of impaction to the third molar mineralization in northwestern Chinese population.

Age estimation by third molar mineralization has been developed for a period of time. Recent studies showed that impaction status has an influence on the rate of the third molar mineralization in Europids and male Black African populations. In this regard, the present study was conducted to determine whether the impaction status could delay the chronological process of third molar mineralization in northwestern Chinese population too. A total of 3,512 digital orthopantomograms of 1,255 male and 2,257 female northwestern Chinese subjects aged from 11 to 26 years were assessed based on the formation stages described by Demirjian et al. with two modifications. Mineralization stage and impaction status were determined for all third molars. Statistical measures were calculated at stages C-H in the male and female gender for both impacted and non-impacted third molars. It was ascertained that the mean ages with impacted third molars at stages C-H were 0.02-1.42 years higher in males and 0.04-1.52 years higher in females than those with non-impacted third molars, but statistical differences were only found at stages C, D, and E in males and stages D and E in females. The probabilities of being under 14, 16, or 18 years of age with non-impacted third molars were all higher than those with impacted third molars. The results prove that impacted third molars show significant slower mineralization than non-impacted ones at stages D and E in both males and females of northwestern Chinese population. It is recommended to consider the influence of impaction on the rate of third molar mineralization for dental age estimation.

Kupffer cells determine intrahepatic traffic of PEGylated liposomal doxorubicin.

Intrahepatic accumulation dominates organ distribution for most nanomedicines. However, obscure intrahepatic fate largely hampers regulation on their in vivo performance. Herein, PEGylated liposomal doxorubicin is exploited to clarify the intrahepatic fate of both liposomes and the payload in male mice. Kupffer cells initiate and dominate intrahepatic capture of liposomal doxorubicin, following to deliver released doxorubicin to hepatocytes with zonated distribution along the lobule porto-central axis. Increasing Kupffer cells capture promotes doxorubicin accumulation in hepatocytes, revealing the Kupffer cells capture-payload release-hepatocytes accumulation scheme. In contrast, free doxorubicin is overlooked by Kupffer cells, instead quickly distributing into hepatocytes by directly crossing fenestrated liver sinusoid endothelium. Compared to free doxorubicin, liposomal doxorubicin exhibits sustained metabolism/excretion due to the extra capture-release process. This work unveils the pivotal role of Kupffer cells in intrahepatic traffic of PEGylated liposomal therapeutics, and quantitively describes the intrahepatic transport/distribution/elimination process, providing crucial information for guiding further development of nanomedicines.

Effects of drug-induced liver injury on the in vivo fate of liposomes.

Liposomes represent one of the most extensively studied nano-carriers due to their potential in targeted drug delivery. However, the complex in vivo fate, particularly under pathological conditions, presents challenges for clinical translation of liposomal therapeutics. Liver serves as the most important organ for liposome accumulation and metabolism. Unfortunately, the fate of liposomes under pathological liver conditions has been significantly overlooked. This study aimed to investigate the in vivo pharmacokinetic profile and biodistribution profile of liposomes under drug-induced liver injury (DILI) conditions. Two classic DILI animal models, i.e. acetaminophen-induced acute liver injury (AILI) and triptolide-induced subacute liver injury (TILI), were established to observe the effect of pathological liver conditions on the in vivo performance of liposomes. The study revealed significant changes in the in vivo fate of liposomes following DILI, including prolonged blood circulation and enhanced hepatic accumulation of liposomes. Changes in the composition of plasma proteins and mononuclear phagocyte system (MPS)-related cell subpopulations collectively led to the altered in vivo fate of liposomes under liver injury conditions. Despite liver injury, macrophages remained the primary cells responsible for liposomes uptake in liver, with the recruited monocyte-derived macrophages exhibiting enhanced ability to phagocytose liposomes under pathological conditions. These findings indicated that high capture of liposomes by the recruited hepatic macrophages not only offered potential solutions for targeted delivery, but also warned the clinical application of patients under pathological liver conditions.

Effects of PEG antibodies on in vivo performance of LNP-mRNA vaccines.

Polyethylene glycol (PEG) plays important roles in stabilizing and lengthening circulation time of lipid nanoparticle (LNP) vaccines. Nowadays various levels of PEG antibodies have been detected in human blood, but the impact and mechanism of PEG antibodies on the in vivo performance of LNP vaccines has not been clarified thoroughly. By illustrating the distribution characteristics of PEG antibodies in human, the present study focused on the influence of PEG antibodies on the safety and efficacy of LNP-mRNA vaccine against COVID-19 in animal models. It was found that PEG antibodies led to shortened blood circulation duration, elevated accumulation and mRNA expression in liver and spleen, enhanced expression in macrophage and dendritic cells, while without affecting the production of anti-Spike protein antibodies of COVID-19 LNP vaccine. Noteworthily, PEG antibodies binding on the LNP vaccine increased probability of complement activation in animal as well as in human serum and led to lethal side effect in large dosage via intravenous injection of mice. Our data suggested that PEG antibodies in human was a risky factor of LNP-based vaccines for biosafety concerns but not efficacy.

Minimalist Nanovaccine with Optimized Amphiphilic Copolymers for Cancer Immunotherapy.

Cancer vaccines with the ability to elicit tumor-specific immune responses have attracted significant interest in cancer immunotherapy. A key challenge for effective cancer vaccines is the spatiotemporal codelivery of antigens and adjuvants. Herein, we synthesized a copolymer library containing nine poly(ethylene glycol) methyl ether methacrylate-co-butyl methacrylate-co-2-(azepan-1-yl)ethyl methacrylate (PEGMA-co-BMA-co-C7AMA) graft copolymers with designed proportions of different components to regulate their properties. Among these polymers, C-25, with a C7AMA:BMA ratio at 1.5:1 and PEG wt % of 25%, was screened as the most effective nanovaccine carrier with enhanced ability to induce mouse bone marrow-derived dendritic cell (BMDC) maturation. Additionally, RNA-sequencing (RNA-Seq) analysis revealed that C-25 could activate dendritic cells (DCs) through multisignaling pathways to trigger potent immune effects. Then, the screened C-25 was used to encapsulate the model peptide antigen, OVA257-280, to form nanovaccine C-25/OVA257-280. It was found that the C-25/OVA257-280 nanovaccine could effectively facilitate DC maturation and antigen cross-presentation without any other additional adjuvant and exhibited excellent prophylactic efficacy in the B16F10-OVA tumor model. Moreover, in combination with antiprogrammed cell death protein-ligand 1 (anti-PD-L1), the C-25/OVA257-280 nanovaccine could significantly delay the growth of pre-existing tumors. Therefore, this work developed a minimalist nanovaccine with a simple formulation and high efficiency in activating tumor-specific immune responses, showing great potential for further application in cancer immunotherapy.

A 3-dimensional anthropometric evaluation of facial morphology among Chinese and Greek population.

INTRODUCTION: The use of 3-dimensional (3D) facial imaging has taken greater importance as orthodontists use the soft tissue paradigm in the evaluation of skeletal disproportion. Studies have shown that faces defer in populations. To date, no anthropometric evaluations have been made of Chinese and Greek faces. AIM: The aim of this study was to compare facial morphologies of Greeks and Chinese using 3D facial anthropometric landmarks. MATERIALS AND METHODS: Three-dimensional facial images were acquired via a commercially available stereophotogrammetric camera capture system. The 3dMD face system captured 245 subjects from 2 population groups (Chinese [n = 72] and Greek [n = 173]), and each population was categorized into male and female groups for evaluation. All subjects in the group were between 18 and 30 years old and had no apparent facial anomalies. Twenty-five anthropometric landmarks were identified on the 3D faces of each subject. Soft tissue nasion was set as the "zeroed" reference landmark. Twenty landmark distances were constructed and evaluated within 3 dimensions of space. Six angles, 4 proportions, and 1 construct were also calculated. Student t test was used to analyze each data set obtained within each subgroup. RESULTS: Distinct facial differences were noted between the subgroups evaluated. When comparing differences of sexes in 2 populations (eg, male Greeks and male Chinese), significant differences were noted in more than 80% of the landmark distances calculated. One hundred percent of the angular were significant, and the Chinese were broader in width to height facial proportions. In evaluating the lips to the esthetic line, the Chinese population had more protrusive lips. CONCLUSIONS: There are differences in the facial morphologies of subjects obtained from a Chinese population versus that of a Greek population.

Delivery of short chain fatty acid butyrate to overcome Fusobacterium nucleatum-induced chemoresistance.

The gut microbiota is closely associated with the progression of colorectal cancer (CRC) in which Fusobacterium nucleatum (F. nucleatum) was found to induce cancer resistance to chemotherapeutics. To relieve F. nucleatum-induced drug resistance, herein, we found that short-chain fatty acid butyrate can inhibit the growth, enrichment and adhesion of F. nucleatum in colorectal cancer tissues by downregulating the expression of adhesion-associated outer membrane proteins, including RadD, FomA, and FadA, to reduce the colonization and invasion of F. nucleatum and relieve the chemoresistance induced by F. nucleatum. Leveraging the killing effect of butyrate on F. nucleatum, sodium butyrate (NaBu) was encapsulated in liposomes or prepared as NaBu tablets with Eudragit S100 coating and administered by intravenous injection or oral administration, respectively. Interestingly, both intravenous administration of NaBu liposomes and oral delivery of NaBu tablets could effectively inhibit the proliferation of F. nucleatum and significantly improve the therapeutic efficacy of oxaliplatin in mice with subcutaneous colorectal tumors, orthotopic colorectal tumors and even spontaneously formed colorectal tumors. Thus, our work provides a simple but effective formulation of NaBu to relieve F. nucleatum-induced chemoresistance, exhibiting ideal clinical application prospects.

Potential pollution assessment of labile trace metals in Xixi River estuary sediments in Xiamen, China.

The release of trace metals caused by industrial effluents and anthropogenic activities has been recorded in the Xixi River estuary, southern China. However, a thorough understanding of the behavior of trace heavy metals in Xixi River sediments is lacking. A total of 12 sediment cores were collected in June and December in the upper estuary section and mouth of the estuary. Here, an in situ high-resolution sampling technique, namely, diffusive gradients in thin films (DGT), was employed to acquire profiles of trace element concentrations and the release of bioavailable metals from sediments in different seasons. A three-step Community Bureau of Reference (BCR) sequential extraction method was used to explore the chemical speciation of trace metals in different seasons and to thereby assess the release potential of trace elements in sediments. The BCR sequential extraction results showed that the trace metals Fe, Mn, Co and Pb were mainly in the residual fraction, which rarely influences living organisms. The total mobile fractions (F1 + F2 + F3) of all trace metals were higher in winter than in summer, suggesting that accumulation occurred from summer to winter. DGT measurements showed that the intensity of sulfate reduction was higher in summer than in winter because of the high temperatures and high organic matter in summer. The intensity of sulfate and Mn(III/IV) reduction increased from the upper estuary section to the lower estuary. Fe(III) reduction decreased in summer but increased slowly in winter. The Pearson correlation results showed that the release of DGT-labile Co in pore water was related to Mn(III/IV) reduction, while the release of DGT-labile Pb was basically not controlled by the Fe-Mn-S redox transition. Abnormally high DGT-labile Pb concentrations were observed at the sampling station (XR3) closest to the estuary in winter, which might have been caused by the high Pb content in the local micro-sediments.

cRGD enables rapid phagocytosis of liposomal vancomycin for intracellular bacterial clearance.

RGD motif has long been exploited as a versatile tool for targeted drug delivery. However, there are so far no successful clinical translations of RGD functionalized nanomedicines. The lack of comprehensive understanding of their in vivo delivery process poses one of the main obstacles. As a reflection on cRGD-enabled targeting delivery, herein the in vivo fate of cyclic RGD peptide functionalized liposome (cRGD-sLip) and its fundamental mechanism are investigated. cRGD-sLip demonstrates incredibly rapid blood clearance and massive mononuclear phagocytic system (MPS) accumulation after intravenous injection. Phagocytes actively capture cRGD-sLip by recognizing αvß3 integrins and scavenger receptors, urging reinterrogation of RGD enabled targeting delivery. Intracellular infection with microbes invading and persisting in the phagocytic system poses serious threats to global public health. Most antimicrobial agents are unable to penetrate through host cell membrane and achieve optimal intracellular therapeutic concentration, resulting in ineffective bacterial killing. By leveraging the rapid phagocytic uptake, cRGD-sLip demonstrates the capability to facilitate effective targeted drug delivery to bacteria infected macrophages and successfully reduce the bacterial burden in a murine intracellular Methicillin-resistant Staphylococcus aureus (MRSA) infection model, verifying the potential value of cRGD-sLip in improving therapeutic efficacy of existing antibiotics in the treatment of intracellular bacterial infection.

Biocompatiable silk fibroin/carboxymethyl chitosan/strontium substituted hydroxyapatite/cellulose nanocrystal composite scaffolds for bone tissue engineering.

Bone defects arise from trauma, skeletal diseases or tumor resections have become a critical clinical challenge. Biocomposite materials as artificial bone repair materials provide a promising approach for bone regeneration. In this study, we used silk fibroin (SF), carboxymethyl chitosan (CMCS), cellulose nanocrystals (CNCs) and strontium substituted hydroxyapatite (Sr-HAp) to prepare the biocomposite scaffolds of SF/CMCS, SF/CMCS/CNCs, SF/CMCS/CNCs/Sr-HAp. The characterization results showed that all the SF-based scaffolds have a porous sponge-like structure with porosities over 80%. In addition, there was a significant increase in compressive strength of SF/CMCS/Sr-HAp/CNCs scaffold when compared to that of SF/CMCS scaffolds, while maintaining high porosity with lower swelling ratio. All the SF-based scaffolds were non-toxic and had a good hemocompatibility. Comparing to the SF/CMCS scaffold, the scaffolds with addition of Sr-HAp and/or CNCs showed enhanced protein adsorption and ALP activity. In addition, higher expression of osteogenic gene markers such as RUNX2, ALP, OCN, OPN, BSP and COL-1 further substantiated the applicability of SF/CMCS/Sr-HAp/CNCs scaffolds for bone related applications. Hence, this study suggests that SF/CMCS/Sr-HAp/CNCs scaffolds have a potential in non-loading bone repair application.

Genome-wide analysis of poplar SAUR gene family and expression profiles under cold, polyethylene glycol and indole-3-acetic acid treatments.

Small auxin-up RNA (SAUR) proteins play an important role in the regulation of plant growth and development. Here, we identified 105 SAUR genes and comprehensively analyzed them in Populus trichocarpa. Based on the phylogenetic relationships, the PtSAURs were classified into ten subfamilies. Of the 105 PtSAURs, 100 were randomly distributed along the nineteen chromosomes, while the remaining genes were located along unassigned scafoolds. These genes mainly evolved through segmental duplications. In total, 94 PtSAURs contained no introns, and each group had a similar conserved motif structure. A promoter analysis revealed various cis-elements related to growth, development and stress responses, and a synteny analysis established orthologous relationships among SAURs in Arabidopsis, rice, grape and poplar. The qRT-PCR and tissue expression analyses indicated that PtSAURs show different expression levels in various tissues in response to different treatments. PtSAUR53 was located on the nuclear and plasma membrane by conducting subcellular localization analysis. This study provides a comprehensive overview of poplar SAUR proteins and a foundation for further investigations for functional analysis of SAURs in poplar growth and development. At the same time, it will be valuable to further study the poplar SAUR genes to reveal their biological effects.

In vivo corrosion behavior of Mg-Mn-Zn alloy for bone implant application.

Magnesium alloy has been implanted in rats to investigate the in vivo degradation behavior of magnesium for bone implant application. After 9 weeks postoperation, 100% implants were fixed and no inflammation was observed. Histological analysis showed new bone was formed around magnesium implant and no difference was found in the histological microstructure of the new bone and the cortical bone. A degradation or reaction layer, which was mainly composed of Ca, P, O, and Mg, was formed on the surface of magnesium alloy implants. High Ca content in the degradation layer displayed that magnesium could promote the deposition of Ca. Residual area calculation has showed that 10-17% magnesium alloy implant has been degraded in vivo. Compared with that of the controlled rats, no increase in serum magnesium and no disorder of kidney were observed after 15 weeks postoperation. After 18 weeks postoperation, 100% magnesium implants were fixed and no inflammation was observed. About 54% magnesium implant has degraded in vivo. Element analysis showed that Zn and Mn in Mg-Mn-Zn alloy distributed homogeneously in the residual magnesium implant, the degradation layer, and the surrounding bone tissue after 18 weeks implantation, indicating that Zn and Mn elements were easily absorbed by bioenvironment.

Cooperation between ligninolytic enzymes produced by superior mixed flora.

Since the ability to degrade lignin with one kind of white-rot fungi or bacteria was very limited, superior mixed flora's ability to degrade lignin was investigated by an orthogonal experiment in this paper. The results showed that superior mixed flora reinforced the ability to degrade lignin, the degradation rates of both sample 9 and 10 were beyond 80% on the day 9. The cooperation between lignin peroxidase (LiP), Mn-dependent peroxidase (MnP) and laccase (Lac) for lignin degradation was also studied. By examining the activities of three enzymes produced by superior mixed flora, it was found that Lac was a key enzyme in the process of biological degradation of lignin but Lip was not; the enzyme activity ratios of Lac/MnP and Lac/LiP were significantly correlative with the degradation rate of lignin at the 0.01 level; and the ratio of MnP/LiP was an important factor affecting the degradation rate of lignin.

Effect of remaining dentin thickness on microtensile bond strength of current adhesive systems.

The purpose of this study was to evaluate the effect of remaining dentin thickness (RDT) on the bond strength of current adhesive systems. Third molars were randomly allocated among four groups depending on the adhesive system used: Clearfil SE Bond ONE (SE1), G-Bond PLUS (GB), BeautiBond (BB), and Clearfil Mega Bond (MB). Bonded specimens were stored in water at 37°C for 24 h. Teeth were then sectioned perpendicular to the adhesive interface to produce beams. After measuring RDT of each beam, microtensile bond strength test was carried out using a universal testing machine at a crosshead speed of 1 mm/min. All data were analyzed by linear regression analysis. Bond strengths of one-step self-etch materials used in this study increased with an increase in RDT. In contrast, that of two-step self-etch adhesive system was not affected by RDT.

Frequency selectivity in pulse responses of Pt/poly(3-hexylthiophene-2,5-diyl)/polyethylene oxide +Li+/Pt hetero-junction.

Pt/poly(3-hexylthiophene-2,5-diyl)/polyethylene oxide + Li+/Pt hetero junctions were fabricated, and their pulse responses were studied. The direct current characteristics were not symmetric in the sweeping range of ±2 V. Negative differential resistance appeared in the input range of 0 to 2 V because of de-doping (or reduction) in the side with the semiconductor layer. The device responded stably to a train of pulses with a fixed frequency. The inverse current after a pulse was related to the back-migrated ions. Importantly, the weight calculated based on the inverse current strength, was depressed during low-frequency stimulations but was potentiated during high-frequency stimulations when pulses were positive. Therefore, frequency selectivity was first observed in a semiconducting polymer/electrolyte hetero junction. Detailed analysis of the pulse response showed that the input frequency could modulate the timing of ion doping, de-doping, and re-doping at the semiconducting polymer/electrolyte interface, which then resulted in the frequency selectivity. Our study suggests that the simple redox process in semiconducting polymers can be modulated and used in signal handling or the simulation of bio-learning.