Common structure of saccades and microsaccades in visual perception.

We obtain large amounts of external information through our eyes, a process often considered analogous to picture mapping onto a camera lens. However, our eyes are never as still as a camera lens, with saccades occurring between fixations and microsaccades occurring within a fixation. Although saccades are agreed to be functional for information sampling in visual perception, it remains unknown if microsaccades have a similar function when eye movement is restricted. Here, we demonstrated that saccades and microsaccades share common spatiotemporal structures in viewing visual objects. Twenty-seven adults viewed faces and houses in free-viewing and fixation-controlled conditions. Both saccades and microsaccades showed distinctive spatiotemporal patterns between face and house viewing that could be discriminated by pattern classifications. The classifications based on saccades and microsaccades could also be mutually generalized. Importantly, individuals who showed more distinctive saccadic patterns between faces and houses also showed more distinctive microsaccadic patterns. Moreover, saccades and microsaccades showed a higher structure similarity for face viewing than house viewing and a common orienting preference for the eye region over the mouth region. These findings suggested a common oculomotor program that is used to optimize information sampling during visual object perception.

Abnormalities in acute salivary biochemical characteristic responses to gustatory stimulation with citric acid in chronic non-atrophic gastritis.

BACKGROUND AND AIM: Salivary characteristics are altered in gastrointestinal diseases and related to oral taste disorder. However, specific salivary biochemical characteristics and their relationships with oral taste disturbances in chronic non-atrophy gastritis (CNAG) remain uncertain. METHODS: Seventy patients with CNAG and 70 subjects in healthy control group (HCG) were enrolled in our study. The levels of salivary flow rate (SFR), pH, salivary α-amylase (sAA) activity, total protein density (TPD), chloride concentration, and calcium concentration were determined before and after citric acid stimulation and compared between CNAG with and without oral taste disturbances. RESULTS: Average body mass index (BMI) of CNAG (17.75 ± 2.08) was lower than that of HCG (21.96 ± 1.72, P < 0.01). Compared with HCG, CNAG showed increased TPD and calcium concentration but decreased SFR both before and after acid stimulation (P < 0.01), as well as reduced sAA and salivary chloride responses to acid stimulation (P < 0.01). Compared with CNAG with normal BMI (24.29%, 17/70), sAA activity response to acid stimulation was reduced in those with low BMI (75.71%, 53/70, P < 0.05). Under resting condition, CNAG with dry mouth (55.71%, 39/70) showed increased SFR and decreased TPD (P < 0.05), as compared with CNAG without dry mouth (44.29%, 31/70). Compared with CNAG without bitter taste (57.14%, 40/70), pH was decreased in those with bitter taste (42.86%, 30/70) under both resting and stimulated conditions (P < 0.05). CONCLUSION: Decreased sAA activity may reflect malnutrition state and be one potential marker of poor digestion, decreased salivary pH may contribute to bitter taste perception, and reduced TPD might be a cause of dry mouth in CNAG.

The benefit of making voluntary choices generalizes across multiple effectors.

It has been shown that cognitive performance could be improved by expressing volition (e.g., making voluntary choices), which necessarily involves the execution of action through a certain effector. However, it is unclear if the benefit of expressing volition can generalize across different effectors. In the present study, participants made a choice between two pictures either voluntarily or forcibly, and subsequently completed a visual search task with the chosen picture as a task-irrelevant background. The effector for choosing a picture could be the hand (pressing a key), foot (pedaling), mouth (commanding), or eye (gazing), whereas the effector for responding to the search target was always the hand. Results showed that participants responded faster and had a more liberal response criterion in the search task after a voluntary choice (vs. a forced choice). Importantly, the improved performance was observed regardless of which effector was used in making the choice, and regardless of whether the effector for making choices was the same as or different from the effector for responding to the search target. Eye-movement data for oculomotor choice showed that the main contributor to the facilitatory effect of voluntary choice was the post-search time in the visual search task (i.e., the time spent on processes after the target was found, such as response selection and execution). These results suggest that the expression of volition may involve the motor control system in which the effector-general, high-level processing of the goal of the voluntary action plays a key role.

CHN nanocomposites and nanocoating resist enamel white spot lesions by enhancing remineralization and antibacterial activity.

Enamel white spot lesions (WSLs) are usually caused by the dissolution of minerals (mainly calcium and phosphate) on the tooth surface due to the acidic environment in the oral cavity. Without timely intervention, WSLs may lead to white spots or a sense of transparency on the tooth surface, and even the formation of dental caries (tooth decay) in severe cases. The key to preventing and treating WSLs is inhibiting the activity of acid-producing bacteria and promoting the remineralization of demineralized enamel. In this study, the network structure formed by sodium tripolyphosphate (TPP) cross-linked chitosan was used to stabilize calcium phosphate, and the multifunctional nanocomposite was constructed by integrating antibacterial components of traditional Chinese medicine, honokiol nanoparticles (HK-NPs) and sodium fluoride to achieve the purpose of resisting cariogenic bacteria and remineralizing with sustained release of calcium and phosphate ions. Notably, we enhanced the remineralization effect of nanocomposites with the help of functional nanocoatings inspired by the mussel biomimetic coating. The experimental results show that the synergistic remineralization effect of nanocomposite and nanocoating is better than that of a single strategy. This multi-prong treatment strategy provides the theoretical and experimental basis for the clinical prevention and treatment of WSLs.

Effects of non-pharmacological interventions on pain in wound patients during dressing change: A systematic review.

BACKGROUND: Changes to the wound dressing frequently cause pain. Some adverse side effects of pharmacologic pain management may cause problems or even impede wound healing. There is no systematic study of non-pharmacologic therapies for pain during wound dressing changes, despite the gradual promotion of non-pharmacologic pain reduction methods. OBJECTIVES: To give clinical wound pain management a new direction, locating and assessing non-pharmacological interventions regarding pain brought on by wound dressing changes are necessary. METHOD: The researchers conducted a comprehensive literature review on non-pharmacological interventions for pain during wound dressing changes across five databases: PubMed, Web of Science, Medline, Embase, and the Cochrane Library spanning the period from January 2010 to September 2022. The evaluation of literature and data extraction was carried out independently by two researchers, and in cases of disagreement, a third researcher participated in the deliberation. To assess the risk of bias in the literature, the researchers utilised the Cochrane Handbook for Reviews of Interventions, version 5.1.0. RESULTS: In total, 951 people were involved in 11 investigations covering seven non-pharmacological therapies. For pain triggered by dressing changes, virtual reality (VR) distraction, auditory and visual distractions, foot reflexology, religious and spiritual care, and guided imaging demonstrated partially positive effects, with hypnosis therapy and jaw relaxation perhaps having a weak effect. CONCLUSION: The key to managing wounds is pain management. According to our review, there is some indication that non-pharmacologic interventions can help patients feel less discomfort when having their wound dressings changed. However, the evidence supporting this view is weak. It needs to be corroborated by future research studies with multicentre and large samples. To promote and use various non-pharmacologic interventions in the future, it is also necessary to build standardised and homogenised paths for their implementation.

Effects of predictive nursing intervention on cognitive impairment and neurological function in ischemic stroke patients.

BACKGROUND: Ischemic stroke is a clinical emergency caused by insufficient intracranial blood supply, which eventually leads to brain tissue necrosis and neurological impairment. Predictive nursing intervention has achieved impressive success in the nursing of multiple surgeries. However, the role of predictive nursing intervention in the care of patients with ischemic stroke remains unclear. METHODS: This study was a randomized controlled trial. Based on the inclusion and exclusion criteria, 126 patients were randomly assigned into two groups, namely the control group and the predictive nursing intervention group. Both groups were treated with thrombolytic therapy with alteplase. The patients in the control group were given routine nursing intervention and the predictive nursing intervention group received additional predictive care. Neurologic functions and cognitive impairment were evaluated by National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer assessment (FMA), Montreal cognitive assessment (MoCA), and mini-mental state examination (MMSE) scales, respectively. Door-to-Needle Times, venous thromboembolism (VTE)-related parameters, and complications were recorded. RESULTS: Predictive nursing intervention significantly shortened the Door-to-Needle Times and enhanced the peak/average femoral venous blood flow and femoral venous diameter. In addition, predictive nursing intervention improved the NIHSS, FMA, MMSE, and MoCA scores and remarkably reduced the recurrence of ischemic stroke, deep vein thrombosis and gingival bleeding. CONCLUSION: Predictive nursing intervention is beneficial to improve the effects of thrombolytic therapy in patients with ischemic stroke, which improves the neurological, cognitive and motor functions of patients, and reduces the occurrence of complications, suggesting an important clinical application value.

Whole exome sequencing facilitated the diagnosis in four Chinese pediatric cases of Joubert syndrome related disorders.

OBJECTIVES: Joubert syndrome is a spectrum of rare genetic disorders, mainly characterized by a distinctive cerebellar and brain stem malformation called the "molar tooth sign" (MTS), hypotonia, and intellectual disability/developmental delay. METHODS: In this study, 4 pediatric cases with developmental delay and oculomotor abnormities were recruited, and submitted to a clinical evaluation and magnetic resonance imaging (MRI) examination. Afterwards, genetic detection with whole exome sequencing (WES) was conducted on the 4 patients. RESULTS: Imaging results demonstrated cerebellar dysplasia in all probands, yet the MTS findings varied in severity. WES detected diagnostic variations in all four probands, which were distributed in four genes, namely CC2D2A, NPHP1, AHI1, and C5orf42. Two variants were novelly identified, which were the CC2D2A: c.2444delC (p.P815fs*2) and the AIH1: exon (15-17) del. In silico analysis supported the pathogenicity of the variations in this study. CONCLUSIONS: Our findings expanded the mutation spectrum of Joubert syndrome related disorders, and provided solid evidence to the affected families for further genetic counseling and pregnancy guidance.

Decreased salivary α-amylase activity responding to citric acid stimulation in Myasthenia gravis with malnutrition.

OBJECTIVES: Malnutrition, defined according to Nutritional risk screening (NRS 2002), is commonly observed in patients of Myasthenia gravis (MG), a neuromuscular disorder manifested by varied degrees of skeletal muscle weakness. Because biochemical composition of saliva changes in correspondence to alterations in nutritional status, we tested our hypothesis that a certain saliva component(s) might serve as a biomarker(s) for nutrition status of MG, particularly for those MG patients with high risk of malnutrition. MATERIALS AND METHODS: 60 MG patients and 60 subjects belonging to the healthy control group (HCG) were enrolled in this case-control study. The salivary α-amylase (sAA) activity, salivary flow rate (SFR), pH, total protein density (TPD), and the concentrations of chloride and calcium ions in MG group with or without malnutrition were measured before and after citric acid stimulation. Thereafter, the relationship between sAA activity and BMI was determined in MG and HCG. RESULTS: Compared with HCG, more patients with malnutrition, increased TPD and chloride and calcium concentrations but decreased pH value and SFR both before and after acid stimulation, as well as reduced sAA activity, pH and TPD responses to acid stimulation. MG with malnutrition showed decreased sAA activity and TPD responding to acid stimulation compared with those without malnutrition. Compared with normal BMI, sAA activity response to acid stimulation was reduced in low BMI. There was a significant strong positive correlation between the ratio of sAA activity and BMI in MG. CONCLUSIONS: Salivary biochemical characteristics are abnormally altered in MG with malnutrition. Altered sAA activity responding to acid stimulation was associated with malnutrition. CLINICAL RELEVANCE: Decreased sAA activity responding to acid stimulation can reflect malnutrition state and may be one potential screening marker for MG patients with high risk of malnutrition.

Cisplatin-loaded polymeric complex micelles with a modulated drug/copolymer ratio for improved in vivo performance.

This study aimed to evaluate the performance of cisplatin-loaded polymeric micelles (CDDP-PMs) with different drug/copolymer ratios of 1:1, 1:3 and 1:6 (w/w) prepared by coordinated complexation and self-assembly method. The mass ratio influenced the self-assembly behaviors and the complex degree, where both single- and double- complexation existed in CDDP-PMs. With the increase of CDDP/copolymer ratio, the particle size and drug loading increased, while encapsulation efficiency decreased. The PEG density of CDDP-PM1-6, CDDP-PM1-3 and CDDP-PM1-1 were 0.20, 0.61 and 0.38 PEG/nm2, respectively. CDDP-PM1-3 and CDDP-PM1-6 had similar sustained release behavior, while CDDP-PM1-1 showed burst release. Pharmacokinetics showed the AUC of CDDP-PM1-6, CDDP-PM1-3 and CDDP-PM1-1 was 27.2, 76.6 and 13.0 fold higher than CDDP solution. Tissue distribution presented the platinum concentration of CDDP-PM1-6, CDDP-PM1-3 and CDDP-PM1-1 was 1.03, 0.80 and 0.48 times of CDDP solution in kidney at 10 min, and 17.61, 28.63 and 16.6 times in tumor at 48 h respectively, indicating CDDP-PMs significantly reduced nephrotoxicity and increased tumor-targeting accumulation. In vivo antitumor test showed that CDDP-PMs exhibited an improved antitumor efficacy and lower systemic toxicity compared with CDDP solution. From CDDP-PM1-1 to CDDP-PM1-6, the toxicity decreased with the increase of copolymer ratio, but the tumor inhibition rate also decreased. CDDP-PM1-3 had relative high therapeutic effect and low toxicity compared with other formulations. CDDP-PM1-3 could improve the antitumor efficacy by increasing the dose within systemic tolerability, but CDDP solution cannot. This work provides an effective strategy by modulating drug/copolymer ratio of CDDP-PMs to balance the antitumor efficacy and toxicity for better payoff. STATEMENT OF SIGNIFICANCE: Cancer chemotherapy always exists a contradiction between antitumor efficacy and toxicity. Higher efficacy against tumor often associated with larger toxicity for normal tissues. This work provides an important strategy by modulating the drug/copolymer ratios to balance the antitumor efficacy and toxicity to obtain better payoff. The cisplatin-loaded polymeric micelles (CDDP-PMs) based on the complexation between CDDP and copolymer with different mass ratios make differences in vitro and in vivo because of the single- or double-complexation degree. Most importantly, we found the balance at CDDP/copolymer ratio of 1:3, which has relative high therapeutic effect and low toxicity compared with other formulations. CDDP-PM1-3 could improve the antitumor efficacy by increasing the dose within systemic tolerability, but CDDP solution cannot.

Protein-based inverse opals: A novel support for enzyme immobilization.

In this study, protein-based inverse opals were prepared for the first time by using the colloidal crystal templating method. The preparation process involved three steps including filling the templates with protein molecules, crosslinking, and template removal. The obtained inverse opals were used to immobilize Penicillin G acylase (PGA) because of its intrinsic biocompatible property. The immobilization process was optimized and the properties of the immobilized PGA (PGA@IO) were investigated. PGA@IO exhibited improved thermal and pH stability compared with its free counterpart. After reusing nine times, it retained 70% of the initial activity. Besides, the PGA@IO retained high activity during the hydrolysis reactions in continuous catalysis in packed-bed reactor (PBR) after 15 days.

[Effect of 3 saliva collection methods on salivary secretion].

PURPOSE: This study compared the effect of 3 saliva collection methods on salivary secretion, in order to select optimum collection method for follow-up studies. METHODS: Fifty-five young healthy volunteers' saliva samples were collected by EP tube collecting emulated with natural flow (ETC), rotating mouth swab slightly (RMS) and chewing mouth swab (CMS) before and after stimulating with acid. The salivary flow rate, salivary alpha-amylase (sAA) activity of each saliva sample and its ratio before and after stimulating with acid were detected to provide the basis for the preferred method of collecting saliva. SPSS 17 software package was used to compare the results before and after acid stimulation. RESULTS: The salivary flow rate ratio (1.73 ± 1.35 and 1.37 ± 0.82, respectively), sAA activity ratio (1.22 ± 0.38 and 1.10 ± 0.30, respectively) and unit time total sAA activity ratio (2.12 ± 1.57 and 1.56 ± 1.18, respectively) of ETC and RMS increased after acid stimulation with the same tendency, and the detection rate of the indexes were closer between ETC and RMS (salivary flow rates: 80%, 78.2%; sAA activity:67.3%, 60.0%; unit time total sAA activity: 83.6%, 76.4%, respectively). Among them, RMS had the advantage of objective and paralleled to collect sufficient amount of saliva. However, the results of CMS were quite different with the first two methods. The detection rate of each index ratio increased in the CMS (salivary flow rate, sAA activity and unit time total sAA activity were 67.3%, 40%, 61.8%, respectively) was significantly lower than the first two, and did not accurately reflect the status of sAA activity in healthy people after acid stimulation. CONCLUSIONS: RMS is recommended when studying on the variation of salivary secretion before and after salivary gland stimulated by acid.

Dual-responsive mPEG-PLGA-PGlu hybrid-core nanoparticles with a high drug loading to reverse the multidrug resistance of breast cancer: an in vitro and in vivo evaluation.

In this study, monomethoxy (polyethylene glycol)-b-P (d,l-lactic-co-glycolic acid)-b-P (l-glutamic acid) (mPEG-PLGA-PGlu) nanoparticles with the ability to rapidly respond to the endolysosomal pH and hydrolase were prepared and the pH-sensitivity was tuned by adjusting the length of the PGlu segment. The mPEG5k-PLGA20k-PGlu (60) nanoparticles were specifically responsive to an endosomal pH of 5.0-6.0 due to the configuration transition of the PGlu segment and rapidly initiated chemical degradation after incubation with proteinase k for 10 min. Doxorubicin hydrochloride (DOX), used as a model drug, was easily encapsulated into nanoparticles and the DOX-loaded nanoparticles (DOX-NPs) exhibited a pH-dependent and enzyme-sensitive release profile in vitro. The dual sensitivity enabled the rapid escape of DOX-loaded nanoparticles from the endolysosomal system to target cellular nuclei, which resulted in increased cell toxicity against MCF/ADR resistant breast cancer cells and a higher cellular uptake than free DOX. In Vivo Imaging studies indicated that the nanoparticles could continuously accumulate in the tumor tissues through EPR effects and Ex vivo Imaging biodistribution studies indicated that DOX-NPs increased drug penetration into tumors compared with normal tissues. The in vivo antitumor activity demonstrated that DOX-loaded NPs had less body loss and a significant regression of tumor growth, indicating the increased anti-tumor efficacy and lower systemic toxicity. Therefore, this dual sensitive nanoparticle system may be a potential nanocarrier to overcome the multidrug resistance exhibited by breast cancer.

Self-Assembled Monomethoxy (Polyethylene Glycol)-b-P(D,L-Lactic-co-Glycolic Acid)-b-P(L-Glutamic Acid) Hybrid-Core Nanoparticles for Intracellular pH-Triggered Release of Doxorubicin.

Triblock copolymers, Monomethoxy (Polyethylene glycol)-b-P(D,L-lactic-co-glycolic acid)-b-P(L-glutamic acid) (mPEG-PLGA-PGlu) with different molecular weights, were synthesized and mPEG(5k)-PLGA(20.5k)-PGlu(7.9k) were self-assembled into negatively charged nanoparticles with a hybrid core of PLGA and PGlu, and a stealth PEG shell. Because of electrostatic interaction with the negative hybrid-core, the model drug, doxorubicin (DOX), could be easily loaded into the hybrid-core nanoparticles with a high drug loading of ca. 25%. The hydrophobic interaction provided by PLGA could increase the stability of drug-loaded nanoparticles with no change in particle size for at least 3 days and only minor drug leakage (< 0.5%) in pH7.4 physiological media. Due to protonation of PGlu block in pH5.0 medium, the hybrid-core of these nanoparticles was destroyed, as shown by transmission electron microscopy, and this resulted in an increase in the pH-triggered release of DOX from 38.9% in pH7.4 release medium to 71% in pH5.0 release medium at 24 h. In vitro cytotoxicity testing involving MCF-7 and NCI-H460 cells showed that DOX-loaded nanoparticles were more cytotoxic to both types of cells than free DOX. Time-dependent cellular uptake of the drug-loaded nanoparticles was observed and at least 4 hours was required for rapid internalization through caveolinmediated endocytosis and macropinocytosis by MCF-7 cells into the endosomes where pH-trigged release of DOX from the nanoparticles occurred. The hybrid-core nanoparticles represent a potentially useful therapeutic delivery system for cationic drugs due to their high drug loading, high stability in physiological media and intracellular pH-triggered release.

A new graphene oxide/polypyrrole foam material with pipette-tip solid-phase extraction for determination of three auxins in papaya juice.

A new material, graphene oxide/polypyrrole (GO/Ppy), was synthesized by mixing graphene oxide and polypyrrole in a specific proportion. It possesses a unique structure similar to that of foam. A homemade pipette-tip solid-phase extraction (PT-SPE) device, which is more simple and convenient than traditional devices, was used for saving reagents and operation time. When GO/Ppy was used as the adsorbent of PT-SPE for determining three auxins (indole-3-propionic acid, indole-3-butyric acid, and 1-naphthaleneacetic acid) present in trace amounts in papaya juice, it showed high affinity and adsorption capacity for all the three auxins. GO/Ppy-PT-SPE also had a significant capacity for eliminating the interferences from the papaya juice matrix. Under optimized conditions, a good linearity of auxins was obtained in the range 16.3-812.5 ng g(-1); the average recoveries at the three spiked levels of the three auxins ranged from 89.4% to 105.6% with the relative standard deviations ≤ 3.0%. Meanwhile, six papaya juice samples with different growth stages were analyzed under optimum conditions, and trace auxins in the range 18.3-100.6 ng g(-1) were observed. Because of its high selectivity, simplicity, and reliability, the GO/Ppy-PT-SPE method developed herein can be potentially applied for determining trace auxins in complex biological samples.

Water-compatible molecularly imprinted microspheres in pipette tip solid-phase extraction for simultaneous determination of five fluoroquinolones in eggs.

New water-compatible molecularly imprinted microspheres were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using 3-(2-carboxyethylsulfanylthiocarbonyl-sulfanyl) propionic acid as a hydrophilic chain-transfer agent, and employed as the sorbent of pipet tip molecularly imprinted solid-phase extraction (PT-MISPE) for rapid extraction and screening of ofloxacin, pefloxacin, norfloxacin, ciprofloxacin, and enrofloxacin in eggs. In comparison to conventional SPE methods, the presented PT-MISPE showed special selectivity, easy operation, and accessible device without expensive SPE apparatus. The presented PT-MISPE method combined advantages of dummy molecularly imprinted polymers and pipet tip solid-phase extraction. The presented method was linear over a calibration range of 25-2500 µg/kg with the limits of detections of 0.53-1.07 µg/kg. Good recoveries (89.1-102.5%) were achieved with relative standard deviations of 2.6-4.8%.

Generation of tooth-like structures from integration-free human urine induced pluripotent stem cells.

BACKGROUND: Tooth is vital not only for a good smile, but also good health. Yet, we lose tooth regularly due to accidents or diseases. An ideal solution to this problem is to regenerate tooth with patients' own cells. Here we describe the generation of tooth-like structures from integration-free human urine induced pluripotent stem cells (ifhU-iPSCs). RESULTS: We first differentiated ifhU-iPSCs to epithelial sheets, which were then recombined with E14.5 mouse dental mesenchymes. Tooth-like structures were recovered from these recombinants in 3 weeks with success rate up to 30% for 8 different iPSC lines, comparable to H1 hESC. We further detected that ifhU-iPSC derived epithelial sheets differentiated into enamel-secreting ameloblasts in the tooth-like structures, possessing physical properties such as elastic modulus and hardness found in the regular human tooth. CONCLUSION: Our results demonstrate that ifhU-iPSCs can be used to regenerate patient specific dental tissues or even tooth for further drug screening or regenerative therapies.

The efficacy and safety of bufadienolides-loaded nanostructured lipid carriers.

Bufadienolides-loaded nanostructured lipid carriers (BU-NLC) were prepared for parenteral application using glyceryl monostearate as solid core, medium-chain triglyceride and oleic acid as liquid lipid material, and Lipoid E-80, sodium deoxycholate and pluronic F68 as stabilizers. In this study, the in vitro cytotoxicity, pharmacokinetics, biodistribution, antitumor efficacy and safety of BU-NLC were evaluated. Against human astrocytoma cell line (U87-MG) and human gastric carcinoma cell line (HGC-27) BU-NLC exhibited cytotoxicity that was similar to that of the free drug, and superior to that of the commercially available fluorouracil injection. BU-NLC exhibited a linear pharmacokinetic behavior at doses ranging from 0.25 to 1.0 mg/kg. The improved pharmacokinetic profile of bufadienolides when formulated in BU-NLC resulted in a higher plasma concentration and lower clearance after intravenous administration compared with bufadienolides solution (BU-S). A biodistribution study indicated that bufadienolides were mainly distributed in the lung, spleen, brain and kidney, and the longest retention was observed in the brain. A sarcoma-180 tumor model further confirmed the advantages of BU-NLC versus BU-S. Hemolysis and acute toxicity investigations showed that BU-NLC was safe when given by intravenous injection with reduced toxicity. In conclusion, the NLC system is a promising approach for the intravenous delivery of bufadienolides.

Preparation of tri-block copolymer micelles loading novel organoselenium anticancer drug BBSKE and study of tissue distribution of copolymer micelles by imaging in vivo method.

BBSKE (1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)] ethane, PCT: CN02/00412) is a novel organoselenium anticancer drug that plays a role in anticancer through inhibiting TrxR (thioredoxin reductase). In this study, we prepared a tri-block copolymer micelles loading BBSKE utilizing the amphiphilic tri-block copolymers (PEG6000-PLA6000) which we synthesized. And then the characters of the copolymer micelles were investigated. When packaged in polymeric micelles, the water solubility of BBSKE was improved to 0.21 mg/ml. The IC(50) were 7.14 microM, 5.05 microM and 4.23 microM when MCF-7 breast cancer cells were treated with BBSKE after 24h, 48h and 72h. The inhibition effect of polymeric micelles to MCF-7 tumor cells was bettered when folate, whose receptor was highly expressed in various tumors, was coated on the surface of these nanoparticles. Finally, by adopting a new way of imaging in vivo, we studied the distribution of micelles in nude mice with and without MCF-7 tumor. The results demonstrated that this copolymer micelles loading BBSKE can accumulate into tumor efficiently.

[Histomorphological effects of Nd:YAG laser for debonding ceramic brackets on rabbit pulp].

OBJECTIVE: Ceramic brackets debonding by Nd:YAG laser is based on the thermal effect of laser, which may cause injury of the pulp tissue. In this study, the histological changes of pulp tissue that subjected to Nd: YAG laser irradiation with different power and time were observed. METHODS: 20 New Zealand rabbits were included in this study. Ceramic brackets were bonded to the 4 incisors as routine. The ceramic brackets of left upper teeth that debonded mechanically were used as control group, while the brackets of right upper, left lower and right lower incisors were debonded by laser with 3 W 3 s (group A), 2 W 5 s (group B) and 5 W 2 s (group C) energies, respectively. The teeth were pulled out at 5 minutes, 1 day, 3 days, 1 week and 1 month after the debonding operations. Slides prepared from the pulp tissues of the debonded teeth were used to evaluate the injury of laser. RESULTS: In comparison with the control group, pulp tissue of teeth that exposed to laser with different energy for 5 minutes showed mild capillary dilation. One day later, group A, B and C showed moderate capillary dilation, and group C also showed moderate infiltration. At 3 days, inflammation was disappeared in group B, whereas capillary dilation was found in group A. Hemorrhage and inflammation cells infiltration were found in group C. At 1 week, alleviation of capillary dilation was found in group A but not in group C. One month later, inflammation disappeared in group A, while pulp tissue in group C showed mild edema and capillary dilation. CONCLUSION: Nd:YAG laser of high energy may cause injury of the pulp tissue during debonding. Laser energy of 3 W 3 s could effectively debond ceramic brackets without irreversible pulp injury.

Requirement of aurora-A kinase in astral microtubule polymerization and spindle microtubule flux.

Mitotic Aurora-A kinase was found to be required for formation of bipolar spindle, ensuring accurate chromosome segregation in mitosis. Recently, Aurora-A was shown to promote Ran-GTP-induced spindle formation and astral microtubule development. Here, by selective immunodepletion, we showed that Aurora-A was required for centrosome- but not Ran-GTP-induced astral microtubule formation in Xenopus egg extracts. Aurora-A enhanced microtubule polymerization in both centrosome- and Ran-GTP-induced aster assemblies: shortening the timing of aster assembly and increasing the aster size. Indeed, adding of Aurora-A protein alone induced microtubule clustering, which was abrogated by Aurora kinase inhibitory small molecule ZM447439. In addition, we showed that Aurora-A was indispensable for Ran-GTP-induced bipolar spindle formation. Inhibition of Aurora-A activity by adding of kinase inactive dominant mutant led to spindle collapse and formation of monopolar spindle whereas minus-end motor protein dynein/dynactin inhibitor p50/dynamitin rescued the bipolar structure. Lastly, we revealed that Aurora-A was necessary for microtubule poleward flux and this requirement depended on kinase activity. Thus, we showed that Aurora-A promoted microtubule polymerization and maintained microtubule flux in ensuring proper bipolar spindle assembly.