Development of a bone targeted thermosensitive liposomal doxorubicin formulation based on a bisphosphonate modified non-ionic surfactant.

Bone is among the most common sites of metastasis in cancer patients, so it is an urgent need to develop drug delivery systems targeting tumor bone metastasis with the feature of controlled release. This study aimed to delivery of thermosensitive liposomal doxorubicin to bone for tumor metastasis treatment. First, Brij78 (polyoxyethylene stearyl ether) was conjugated with Pamidronate (Pa). By incorporating Pa-Brij78 to DPPC/Chol liposomes, we developed Pa surface functionalized liposomes. The Pa-Brij78/DPPC/Chol liposomes (PB-liposomes) exhibited a stronger binding affinity to hydroxyapatite (HA), a major component of bone, than Brij78/DPPC/Chol liposomes (B-liposomes). Doxorubicin (Dox) was then encapsulated in PB-liposomes and the results demonstrated complete release of Dox from PB-liposomes or the complex of HA/PB-liposomes within 10 min at 42 °C. Next, human lung cancer A549 cells were treated with the thermosensitive complex of HA/PB-liposomes/Dox to mimic tumor bone metastasis treatment through bone targeted delivery of therapeutic agents. Pre-incubation of HA/PB-liposomes/Dox with mild heat at 42 °C induced subsequent higher cytotoxicity to A549 cells than incubation of the same complex at 37 °C, suggesting more active drug release triggered by heat. In conclusion, we synthesized a novel surfactant Pa-Brij78 and it has the potential to be used for development of a bone targeted thermosensitive liposome formulation for treatment of tumor bone metastasis.

Power-efficient neural network with artificial dendrites.

In the nervous system, dendrites, branches of neurons that transmit signals between synapses and soma, play a critical role in processing functions, such as nonlinear integration of postsynaptic signals. The lack of these critical functions in artificial neural networks compromises their performance, for example in terms of flexibility, energy efficiency and the ability to handle complex tasks. Here, by developing artificial dendrites, we experimentally demonstrate a complete neural network fully integrated with synapses, dendrites and soma, implemented using scalable memristor devices. We perform a digit recognition task and simulate a multilayer network using experimentally derived device characteristics. The power consumption is more than three orders of magnitude lower than that of a central processing unit and 70 times lower than that of a typical application-specific integrated circuit chip. This network, equipped with functional dendrites, shows the potential of substantial overall performance improvement, for example by extracting critical information from a noisy background with significantly reduced power consumption and enhanced accuracy.

The Non-Specific Binding of Fluorescent-Labeled MiRNAs on Cell Surface by Hydrophobic Interaction.

BACKGROUND: MicroRNAs are small noncoding RNAs about 22 nt long that play key roles in almost all biological processes and diseases. The fluorescent labeling and lipofection are two common methods for changing the levels and locating the position of cellular miRNAs. Despite many studies about the mechanism of DNA/RNA lipofection, little is known about the characteristics, mechanisms and specificity of lipofection of fluorescent-labeled miRNAs. METHODS AND RESULTS: Therefore, miRNAs labeled with different fluorescent dyes were transfected into adherent and suspension cells using lipofection reagent. Then, the non-specific binding and its mechanism were investigated by flow cytometer and laser confocal microscopy. The results showed that miRNAs labeled with Cy5 (cyanine fluorescent dye) could firmly bind to the surface of adherent cells (Hela) and suspended cells (K562) even without lipofection reagent. The binding of miRNAs labeled with FAM (carboxyl fluorescein) to K562 cells was obvious, but it was not significant in Hela cells. After lipofectamine reagent was added, most of the fluorescently labeled miRNAs binding to the surface of Hela cells were transfected into intra-cell because of the high transfection efficiency, however, most of them were still binding to the surface of K562 cells. Moreover, the high-salt buffer which could destroy the electrostatic interactions did not affect the above-mentioned non-specific binding, but the organic solvent which could destroy the hydrophobic interactions eliminated it. CONCLUSIONS: These results implied that the fluorescent-labeled miRNAs could non-specifically bind to the cell surface by hydrophobic interaction. It would lead to significant errors in the estimation of transfection efficiency only according to the cellular fluorescence intensity. Therefore, other methods to evaluate the transfection efficiency and more appropriate fluorescent dyes should be used according to the cell types for the accuracy of results.

Radiofrequency thermocoagulation for V2/V3 idiopathic trigeminal neuralgia: effect of treatment temperatures on long-term clinical outcomes: A Cohort Study.

Radiofrequency thermocoagulation (RFT) is widely used to treat trigeminal neuralgia (TN); however, the optimal temperature at which RFT is most efficacious remains under much debate. Thus, the aim of the present study was to determine the lowest temperature at which morbidity could be minimized and patient outcomes maximized.A multivariate analysis was used to study 1354 patients who underwent computed tomography (CT)-guided RFT for V2/V3 idiopathic trigeminal neuralgia (ITN) during from June 2006 to May 2015. RFT was carried out at 62, 65, and 68°C, while keeping all other RF parameters the same. This was a prospective cohort study, in which we assessed intra- and postoperative complications, pain relief, and long-term health-related quality of life (HRQoL).The intraoperative and in-hospital complications of patients were mainly facial hematoma, mouth and external auditory meatus penetration, nausea, vomiting, dizziness, and headache, which were all treated symptomatically. In long-term follow-up, patients with pain relief (defined as no pain and no required drug intervention) at 62, 65, and 68°C accounted for 94.2%, 98.3%, and 98.8% (at discharge); 83.8%, 90.1%, and 91.4% (at 1 year); 66.7%, 80.5%, and 88.2% (at 3 years); 59.0%, 64.3%, and 77.2% (at 5 years); 48.7%, 57.8%, and 72.3% (at 7 years); 40.6%, 53.7%, and 60.3% (at 9 years), respectively. The number of patients with facial numbness, masticatory atonia, or corneal hypoesthesia was increased with the elevation of temperature, but these complications were all mild. No blindness, deafness, intracranial hemorrhage, or death as a result of the surgical intervention occurred in any patients. SF-36 scores showed highest HRQoL in the group treated at 68°C, followed by the 65 and 62°C groups, respectively.Our results demonstrate that 68°C is a good choice for RFT of V2/V3 ITN. The alternative option is 65 or 62°C for RFT to minimize the occurrence of complications including facial numbness, yet which often yields a higher recurrence rate.

Treatment of bilateral idiopathic trigeminal neuralgia by radiofrequency thermocoagulation at different temperatures.

Radiofrequency thermocoagulation (RFT) is an effective treatment for trigeminal neuralgia, but consensus regarding an optimal treatment temperature is lacking. While treatment temperatures ranging from 60°C to 95°C have been reported, RFT at too high a temperature is often followed by serious complications, and comparative evaluations of RFT at different temperatures in a single study are rare.This current prospective cohort study was to compare immediate and long-term outcomes of RFT at varying temperatures in patients with bilateral idiopathic trigeminal neuralgia (ITN) of maxillary division of trigeminal nerve (V2), mandibular division of trigeminal nerve (V3), and V2+V3, including pain relief, complications, recurrence rate, and patient satisfaction. From May 2011 to April 2016, 62 consecutive patients with bilateral ITN of V2, V3, and V2+V3 were enrolled in the study. These patients underwent bilateral RFT at 68°C and 75°C, respectively, using the same RF parameters. Side-to-side results, including pain relief, complications, and patient satisfaction, were compared during a 5-year follow-up period.Overall pain relief was satisfactory after RFT. The rate of pain relief after treatment at 75°C was slightly higher than at 68°C (P > 0.05). The pain-free rate was 95.1% at 75°C and 93.5% at 68°C at 1 year, 84.3% and 78.1% at 3 years, and 80.7% and 74.4% at 5 years. There were 10 and 13 cases of recurrence, respectively, and 6 cases of bilateral recurrence. The incidence and severity of complications were greater at 75°C (P < 0.05) than at 68°C, and therefore the patient satisfaction at the higher temperature was lower (P < 0.05).Patients with bilateral ITN who underwent RFT at different temperatures had consistent pain relief after RFT at both 75°C and 68°C, but there were fewer and less severe complications at 68°C, which was accompanied by greater patient satisfaction. This suggests that RFT at lower temperatures may be preferable, and that a temperature of 68°C can be recommended.

[Distribution Characteristics of Sedimentary Pigments in the Changjiang Estuary and Zhe-Min Coast and its Implications].

Compositions and contents of sedimentary pigments were examined using high performance liquid chromatography in order to discuss the spatial distributions of phytoplankton primary production, phytoplankton functional type and the preservation efficiency of phytoplankton pigments and their influencing factors. The results showed that: chloropigments [Chlorins, including chlorophyll-a (Chl-a) and pheopigments (Pheo-a), such as pheophytin-a (PHtin-a), pheophorbide-a (PHide-a), pPheophytin-a (pPHtin-a), sterol chlorin esters (SCEs) and carotenol chlorin esters (CCEs)] were the major type of sedimentary pigments. The nutrients inputs from Changjiang Diluted Water and upwelling in the Zhe-Min coastal mud area were the major cause for the patchy distribution with high sedimentary chloropigment contents. Carotenoid contents showed no trending changes and exhibited high values in the Changjiang Estuary and Zhe-Min Coasts. Based on the relative proportions of each diagnostic carotenoid to the total diagnostic carotenoids in the sediments, the relative contributions of diatoms, dinoflagellates, prymnesiophytes, prasinophytes, cryptophytes and cyanobacterias in the phytoplankton fuctional types were 48.8% +/- 17.4%, 10.7% +/- 11.5%, 8.1% +/- 7.2%, 18.6% +/- 8.2%, 9.4% +/- 6.4% and 4.3% +/- 3.2%, respectively. The preference for external environmental conditions (e.g., nutrient level and water salinity) was the main cause for the decreasing trends of diatoms and dinoflagellates proportions and the increasing trends of prasinophytes, cryptophytes and cyanobacterias seawards. Based on the spatial distribution of Chl-a/Pheo-a ratios, the higher preservation efficiencies of sedimentary pigments in the coastal regions (e.g., outer edge of maximum turbidity zone in the Changjiang Estuary, mouth of the Hangzhou Bay and upwelling region in the Zhe-Min Coast) were mainly due to the higher sedimentation rate and seasonal occurrences of hypoxia in bottom water, and these regions with higher sedimentary pigment preservation efficiencies were probably ideal areas for the marine eco-environmental evolutions. The bad sedimentary environment caused by the water exchange inside and outside of Hangzhou Bay was the dominant reason for the low sedimentary pigment contents and preservation efficiencies in this region.

[Finite element contact stress analysis of simulating teeth with wedge-shaped defects in the cervical region].

PURPOSE: To study the distribution of stress of simulating teeth with wedge-shaped defects in the cervical region. METHODS: The models of anisotropic enamel of the mandibular first premolar and the opposite maxillary first premolar crown were created. A defect was introduced into the model of mandibular premolar in the buccal cervical region along the enamelo-dentinal junction. The stress distribution in the cervical region of the mandibular premolar was investigated with regard to different loading conditions simulating working, nonworking and vertical micromotions. In each case, the stroke was applied to the mandibular premolars in a stepping procedure using nonlinear contact analysis. RESULTS: The stresses were concentrated in the defect of the enamel and dentin at the enamelo-dentinal junction(EDJ) in the condition of different loading, especially in the condition of simulating lateral excursion on one contact. CONCLUSION: Undermined cervical EDJ had a significant effect on the stress distribution in the buccal cervical region.