Spatiotemporally and Sequentially-Controlled Drug Release from Polymer Gatekeeper-Hollow Silica Nanoparticles

Combination chemotherapy has become the primary strategy against cancer multidrug resistance; however, accomplishing optimal pharmacokinetic delivery of multiple drugs is still challenging. Herein, we report a sequential combination drug delivery strategy exploiting a pH-triggerable and redox switch to release cargos from hollow silica nanoparticles in a spatiotemporal manner. This versatile system further enables a large loading efficiency for both hydrophobic and hydrophilic drugs inside the nanoparticles, followed by self-crosslinking with disulfide and diisopropylamine-functionalized polymers. In acidic tumour environments, the positive charge generated by the protonation of the diisopropylamine moiety facilitated the cellular uptake of the particles. Upon internalization, the acidic endosomal pH condition and intracellular glutathione regulated the sequential release of the drugs in a time-dependent manner, providing a promising therapeutic approach to overcoming drug resistance during cancer treatment.ope

Mechanism and treatment for learning and memory deficits in mouse models of Noonan syndrome.

In Noonan syndrome (NS) 30-50% of subjects show cognitive deficits of unknown etiology and with no known treatment. Here, we report that knock-in mice expressing either of two NS-associated mutations in Ptpn11, which encodes the nonreceptor protein tyrosine phosphatase Shp2, show hippocampal-dependent impairments in spatial learning and deficits in hippocampal long-term potentiation (LTP). In addition, viral overexpression of an NS-associated allele PTPN11(D61G) in adult mouse hippocampus results in increased baseline excitatory synaptic function and deficits in LTP and spatial learning, which can be reversed by a mitogen-activated protein kinase kinase (MEK) inhibitor. Furthermore, brief treatment with lovastatin reduces activation of the GTPase Ras-extracellular signal-related kinase (Erk) pathway in the brain and normalizes deficits in LTP and learning in adult Ptpn11(D61G/+) mice. Our results demonstrate that increased basal Erk activity and corresponding baseline increases in excitatory synaptic function are responsible for the LTP impairments and, consequently, the learning deficits in mouse models of NS. These data also suggest that lovastatin or MEK inhibitors may be useful for treating the cognitive deficits in NS

In Vitro inhibitory activity of Alpinia katsumadai extracts against influenza virus infection and hemagglutination

<p>Abstract</p> <p>Background</p> <p><it>Alpinia katsumadai </it>(AK) extracts and fractions were tested for <it>in vitro </it>antiviral activities against influenza virus type A, specially human A/PR/8/34 (H1N1) and avian A/Chicken/Korea/MS96/96 (H9N2), by means of time-of-addition experiments; pre-treatment, simultaneous treatment, and post treatment.</p> <p>Results</p> <p>In pre-treatment assay, the AK extracts and AK fractions did not show significant antiviral activity. During the simultaneous treatment assay, one AK extract and five AK fractions designated as AK-1 to AK-3, AK-5, AK-10, and AK-11 showed complete inhibition of virus infectivity against A/PR/8/34 (H1N1) and A/Chicken/Korea/MS96/96 (H9N2). The 50% effective inhibitory concentrations (EC₅₀) of these one AK extracts and five AK fractions with exception of the AK-9 were from 0.8 ± 1.4 to 16.4 ± 4.5 <it>μ</it>g/mL against A/PR/8/34 (H1N1). The two AK extracts and three AK fractions had EC₅₀values ranging from <0.39 ± 0.4 to 2.3 ± 3.6 <it>μ</it>g/mL against A/Chicken/Korea/MS96/96 (H9N2). By the hemagglutination inhibition (HI) assay, the two AK extracts and five AK fractions completely inhibited viral adsorption onto chicken RBCs at less than 100 <it>μ</it>g/mL against both A/PR/8/34 (H1N1) and A/Chicken/Korea/MS96/96 (H9N2). Interestingly, only AK-3 was found with inhibition for both viral attachment and viral replication after showing extended antiviral activity during the post treatment assay and quantitative real-time PCR.</p> <p>Conclusions</p> <p>These results suggest that AK extracts and fractions had strong anti-influenza virus activity that can inhibit viral attachment and/or viral replication, and may be used as viral prophylaxis.</p

Anticancer Activity of Ferulic Acid-Inorganic Nanohybrids Synthesized via Two Different Hybridization Routes, Reconstruction and Exfoliation-Reassembly

We have successfully prepared nanohybrids of biofunctional ferulic acid and layered double hydroxide nanomaterials through reconstruction and exfoliation-reassembly routes. From X-ray diffraction and infrared spectroscopy, both nanohybrids were determined to incorporate ferulic acid molecules in anionic form. Micrsocopic results showed that the nanohybrids had average particle size of 150 nm with plate-like morphology. As the two nanohybridization routes involved crystal disorder and random stacking of layers, the nanohybrids showed slight alteration in z-axis crystallinity and particle size. The zeta potential values of pristine and nanohybrids in deionized water were determined to be positive, while those in cell culture media shifted to negative values. According to the in vitro anticancer activity test on human cervical cancer HeLa cells, it was revealed that nanohybrids showed twice anticancer activity compared with ferulic acid itself. Therefore we could conclude that the nanohybrids of ferulic acid and layered double hydroxide had cellular delivery property of intercalated molecules on cancer cell lines

A Wearable Wrist Band-Type System for Multimodal Biometrics Integrated with Multispectral Skin Photomatrix and Electrocardiogram Sensors

Multimodal biometrics are promising for providing a strong security level for personal authentication, yet the implementation of a multimodal biometric system for practical usage need to meet such criteria that multimodal biometric signals should be easy to acquire but not easily compromised. We developed a wearable wrist band integrated with multispectral skin photomatrix (MSP) and electrocardiogram (ECG) sensors to improve the issues of collectability, performance and circumvention of multimodal biometric authentication. The band was designed to ensure collectability by sensing both MSP and ECG easily and to achieve high authentication performance with low computation, efficient memory usage, and relatively fast response. Acquisition of MSP and ECG using contact-based sensors could also prevent remote access to personal data. Personal authentication with multimodal biometrics using the integrated wearable wrist band was evaluated in 150 subjects and resulted in 0.2% equal error rate ( EER ) and 100% detection probability at 1% FAR (false acceptance rate) ( PD.1 ), which is comparable to other state-of-the-art multimodal biometrics. An additional investigation with a separate MSP sensor, which enhanced contact with the skin, along with ECG reached 0.1% EER and 100% PD.1 , showing a great potential of our in-house wearable band for practical applications. The results of this study demonstrate that our newly developed wearable wrist band may provide a reliable and easy-to-use multimodal biometric solution for personal authentication

Airway obstruction by extrinsic tracheal compression during spinal surgery under prone position -A case report-

Tracheal compression by vascular anomalies in adults is uncommon and most related reports are of children. A 79-year-old woman without any respiratory history underwent a lumbar spine surgery under general anesthesia. She suddenly developed airway obstruction after a position change from supine to prone. A fiberoptic bronchoscopy showed the obstruction of endotracheal tube. The obstruction was relieved after we changed the depth of endotracheal tube and supported the patient's neck with a cotton roll. The surgery ended without any other event and the patient recovered safely. A computed tomography revealed the rightward tracheal deviation and tortuous innominate artery contact with trachea. The patient didn't manifest any respiratory related symptoms during postoperative period, and she was discharged without any treatment

Modular Flow Reactors for Valorization of Kraft Lignin and Low???Voltage Hydrogen Production

Recent studies have found that green hydrogen production and biomass utilization technologies can be combined to efficiently produce both hydrogen and value-added chemicals using biomass as an electron and proton source. However, the majority of them have been limited to proof-of-concept demonstrations based on batch systems. Here the authors report the design of modular flow systems for the continuous depolymerization and valorization of lignin and low-voltage hydrogen production. A redox-active phosphomolybdic acid is used as a catalyst to depolymerize lignin with the production of aromatic compounds and extraction of electrons for hydrogen production. Individual processes for lignin depolymerization, byproduct separation, and hydrogen production with catalyst reactivation are modularized and integrated to perform the entire process in the serial flow. Consequently, this work enabled a one-flow process from biomass conversion to hydrogen gas generation under a cyclic loop. In addition, the unique advantages of the fluidic system (i.e., effective mass and heat transfer) substantially improved the yield and efficiency, leading to hydrogen production at a higher current density (20.5 mA cm???2) at a lower voltage (1.5 V) without oxygen evolution. This sustainable eco-chemical platform envisages scalable co-production of valuable chemicals and green hydrogen for industrial purposes in an energy-saving and safe manner