Dendrobium officinale phenolic extract maintains proteostasis by regulating autophagy in a Caenorhabditis elegans model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and accumulating evidence suggested that proteostatic imbalance is a key feature of the disease. Traditional Chinese medicine exhibits a multi-target therapeutic effect, making it highly suitable for addressing protein homeostasis imbalance in AD. Dendrobium officinale is a traditional Chinese herbs commonly used as tonic agent in China. In this study, we investigated protection effects of D. officinale phenolic extract (SH-F) and examined its underlying mechanisms by using transgenic Caenorhabditis elegans models. We found that treatment with SH-F (50 µg/mL) alleviated Aß and tau protein toxicity in worms, and also reduced aggregation of polyglutamine proteins to help maintain proteostasis. RNA sequencing results showed that SH-F treatment significantly affected the proteolytic process and autophagy-lysosomal pathway. Furthermore, we confirmed that SH-F showing maintainance of proteostasis was dependent on bec-1 by qRT-PCR analysis and RNAi methods. Finally, we identified active components of SH-F by LC-MS method, and found the five major compounds including koaburaside, tyramine dihydroferulate, N-p-trans-coumaroyltyramine, naringenin and isolariciresinol are the main bioactive components responsible for the anti-AD activity of SH-F. Our findings provide new insights to develop a treatment strategy for AD by targeting proteostasis, and SH-F could be an alternative drug for the treatment of AD.

Liensinine and neferine exert neuroprotective effects via the autophagy pathway in transgenic Caenorhabditis elegans.

BACKGROUND: Liensinine and neferine are the main bisbenzylisoquinoline alkaloids obtained from the seeds of Nelumbo nucifera, which commonly used as edible food and traditional medicine in Asia. It was reported that liensinine and neferine could inhibit the activities of acetylcholinesterase and cross the blood-brain barriers, suggesting their therapeutic potential for the management of Alzheimer's disease. METHODS: Here, we employed SH-SY5Y human neuroblastoma cells stably transfected with the human Swedish amyloid precursor protein (APP) mutation APP695 (APP695swe SH-SY5Y) as an in vitro model and transgenic Caenorhabditis elegans as an in vivo model to investigate the neuroprotective effects and underlying mechanism of liensinine and neferine. RESULTS: We found that liensinine and neferine could significantly improve the viability and reduce ROS levels in APP695swe SH-SY5Y cells, inhibit ß-amyloid and tau-induced toxicity, and enhance stress resistance in nematodes. Moreover, liensinine and neferine had obviously neuroprotective effects by assaying chemotaxis, 5-hydroxytryptamine sensitivity and the integrity of injured neurons in nematodes. Preliminary mechanism studies revealed that liensinine and neferine could upregulate the expression of autophagy related genes (lgg-1, unc-51, pha-4, atg-9 and ced-9) and reduce the accumulation of ß-amyloid induced autophagosomes, which suggested autophagy pathway played a key role in neuroprotective effects of these two alkaloids. CONCLUSIONS: Altogether, our findings provided a certain working foundation for the use of liensinine and neferine to treat Alzheimer's disease based on neuroprotective effects.

Synthesis and Spatial Order Characterization of Controlled Silica Particle Sizes Organized as Photonic Crystals Arrays.

The natural occurrence of precious opals, consisting of highly organized silica particles, has prompted interest in the synthesis and formation of these structures. Previous research has shown that a highly organized photonic crystal (PhC) array is only possible when it is based on a low polydispersity index (PDI) sample of particles. In this study, a solvent-only variation method is used to synthesize different sizes of silica particles (SiPs) by following the traditional sol-gel Stöber approach. The controlled rate of the addition of the reagents promoted the homogeneity of the nucleation and growth of the spherical silica particles, which in turn yielded a low PDI. The opalescent PhC were obtained via self-assembly of these particles using a solvent evaporation method. Analysis of the spatial statistics, using Voronoi tessellations, pair correlation functions, and bond order analysis showed that the successfully formed arrays showed a high degree of quasi-hexagonal (hexatic) organization, with both global and local order. Highly organized PhC show potential for developing future materials with tunable structural reflective properties, such as solar cells, sensing materials, and coatings, among others.

Mussel-Inspired Adhesive and Self-Healing Hydrogel as an Injectable Wound Dressing.

This study develops a multi-functional hydrogel with a dual injection system based on the adhesive and self-healing properties of the byssus excretion found in mussels. Through precisely controlling the composite cross-linking hydrophobic association (HA) structure composed of A and B solutions, a high-strength, temperature-sensitive injectable hydrogel can be obtained, and it has good self-healing properties. The main composition of A solution contains the surfactant SDS, which can form amphiphilic micelles, the strength increasing component stearyl methacrylate (C18), and NIPAAm, which provides thermo-sensitivity. Solution B contains dopamine acrylate (DAA), which has self-healing properties, and ferric chloride (FeCl3), which is a connecting agent. The rheological behavior shows that when the temperature is increased from 25 °C to 32 °C, the gel can be completed in seven minutes to form a composite hydrogel of NIPAAm-DAA-HA. When NMR identification was conducted on composite DAA, it was found that when comparing DAA and dopamine hydrochloride there were new peaks with specific characteristics, which confirm that this study successfully prepared DAA; swelling tests found that swelling could surpass a rate of 100%, and a higher ratio of crosslinking agent decreased the amount of moisture absorbed; the results of the compression test showed that the addition of hydrophobic micelles C18 effectively enhanced the mechanical properties of hydrogel, allowing it to withstand increased external stress; the adhesiveness results show that an increase in the catechol-Fe3+ concentration of the NIPAAm-DAA-HA hydrogel results in an increased adhesiveness of 0.0081 kg/cm2 on pig skin; the self-healing tests show that after taking damage, NIPAAm-DAA-HA hydrogel can be reactivated with catechol-Fe3+ and self-heal at a rate of up to 70% after 24 h; antibacterial tests show that hydrogel has good bacterial resistance to against E. coli, staphylococcus epidermidis, and bacillus cereus; through in vitro transdermal absorption, it can be seen that the release ability of drugs within the hydrogel can reach up to 8.87 µg/cm2. The NIPAAm-DAA-HA hydrogel prepared by this study performed excellently in both adhesion and self-healing tests. The thermo-sensitive and antibacterial properties can be applied to the treatment of deep wounds and address some of the flaws of traditional wound dressings.

Fabrication and Characterization of an Efficient Inverted Perovskite Solar Cells with POSS Passivating Hole Transport Layer.

Polyhedral oligomeric silsesquioxane (POSS), featuring a hollow-cage or semi-cage structure is a new type of organic-inorganic hybrid nanoparticles. POSS combines the advantages of inorganic components and organic components with a great potential for optoelectronic applications such as in emerging perovskite solar cells. When POSS is well dispersed in the polymer matrix, it can effectively improve the thermal, mechanical, magnetic, acoustic, and surface properties of the polymer. In this study, POSS was spin-coated as an ultra-thin passivation layer over the hole transporting layer of nickel-oxide (NOx) in the structure of a perovskite solar cell. The POSS incorporation led to a more hydrophobic and smoother surface for further perovskite deposition, resulting in the increase in the grain size of perovskite. An appropriate POSS passivation layer could effectively reduce the recombination of the electron and hole at grain boundaries and increase the short-circuit current from 18.0 to 20.5 mA·cm-2. Moreover, the open-circuit voltage of the cell could slightly increase over 1 V.

Role of lateral amygdala calstabin2 in regulation of fear memory.

Calstabin2, also named FK506 binding protein 12.6 (FKBP12.6), is a subunit of ryanodine receptor subtype 2 (RyR2) macromolecular complex, an intracellular calcium channel. Studies from our and other's lab have shown that hippocampal calstabin2 regulates spatial memory. Calstabin2 and RyR2 are widely distributed in the brain, including the amygdala, a key brain area involved in the regulation of emotion including fear. Little is known about the role of calstabin2 in fear memory. Here, we found that genetic deletion of calstabin2 impaired long-term memory in cued fear conditioning test. Knockdown calstabin2 in the lateral amygdala (LA) by viral vector also impaired long-term cued fear memory expression. Furthermore, calstabin2 knockout reduced long-term potentiation (LTP) at both cortical and thalamic inputs to the LA. In conclusion, our present data indicate that calstabin2 in the LA plays a crucial role in the regulating of emotional memory.

Nociceptin impairs acquisition of novel object recognition memory in perirhinal cortex.

Nociceptin/Orphanin FQ (N/OFQ) plays an important role in the regulation of spatial, fear and recognition memories. N/OFQ receptors are highly distributed in the perirhinal cortex, which is a key brain area involved in modulating novel object recognition (NOR) memory. However, the role of N/OFQ in NOR memory in the perirhinal cortex was still unknown. Moreover, the effects of N/OFQ on different stages of NOR memory were still unclear. In NOR task, we found that pre-training intracerebroventricular (icv) injection of N/OFQ (0.3 and 1 nmol) impaired long-term memory in a dose-dependent manner. However, icv infusion of N/OFQ immediately after training did not affect NOR memory consolidation even at a high dose of 3 nmol. Pre-test icv injection of N/OFQ (1 nmol) also did not influence NOR memory retrieval. These data indicate that N/OFQ negatively modulates long-term NOR memory during the acquisition phase. Furthermore, the amnesia effect of N/OFQ (1 nmol, icv) could be antagonist by pre-treatment with the selective N/OFQ receptor antagonist [Nphe1]N/OFQ(1-13)NH2 (10 nmol, icv), indicating pharmacological specificity. Then, we found that pre-training infusion of N/OFQ (0.1 and 0.3 nmol/side) into the bilateral perirhinal cortex impaired long-term NOR memory, suggesting the perirhinal cortex is a critical brain structure in mediating the amnesic effect of N/OFQ in NOR task. In conclusion, our data, for the first time, indicate that N/OFQ in the perirhinal cortex impairs NOR memory acquisition through the NOP receptors.

Sustained release of recombinant thrombomodulin from cross-linked gelatin/hyaluronic acid hydrogels potentiate wound healing in diabetic mice.

Thrombomodulin (TM) is a type-I transmembrane glycoprotein expressed on the surfaces of endothelial cells and epidermal keratinocytes. It is known to regulate blood coagulation, inflammation, and cell-cell adhesion. A recombinant TM, which contains an epidermal growth factor-like domain and serine/threonine-riches domain, has been demonstrated to stimulate cell proliferation and migration of keratinocytes and wound healing. In this study, we developed the biodegradable hydrogels and evaluated the efficacy of sustained release of rhTM from the hydrogel for the treatment of diabetic wounds. The hydrogels were composed of gelatin with or without hyaluronic acid, and fabricated by chemical cross-linking followed by lyophilization. Gelatin-based hydrogels had porous structure, good swelling property, and were biodegradable with characteristics of slow rhTM release in a short term. The once every-3-day rhTM-loaded hydrogel (with hyaluronic acid) markedly promoted wound healing and were superior to rhTM solution, once daily rhTM hydrogel (without hyaluronic acid), hydrogel controls, and once every-3-day rhEGF hydrogel treatment groups. The rhTM hydrogels enhanced granulation tissue formation, re-epithelialization, collagen deposition, and angiogenesis in wound repair. The once every-3-day rhTM hydrogel was stable and drug release was maintained up to 11-month of storage at 4 °C. The developed rhTM hydrogels could meet the needs for clinical practice, and may have future medical applications for wound care in diabetic patients.

RNase A Promotes Proliferation of Neuronal Progenitor Cells via an ERK-Dependent Pathway.

Members of the ribonuclease A (RNase A) superfamily regulate various physiological processes. RNase A, the best-studied member of the RNase A superfamily, is widely expressed in different tissues, including brains. We unexpectedly found that RNase A can trigger proliferation of neuronal progenitor cells (NPC) both in vitro and in vivo. RNase A treatment induced cell proliferation in dissociated neuronal cultures and increased cell mass in neurosphere cultures. BrdU (5-Bromo-2'-Deoxyuridine) labeling confirmed the effect of RNase A on cell proliferation. Those dividing cells were Nestin- and SOX2-positive, suggesting that RNase A triggers NPC proliferation. The proliferation inhibitor Ara-C completely suppressed the effect of RNase A on NPC counts, further supporting that RNase A increases NPC number mainly by promoting proliferation. Moreover, we found that RNase A treatment increased ERK phosphorylation and blockade of the ERK pathway inhibited the effect of RNase A on NPC proliferation. Intracerebroventricular injection of RNase A into mouse brain increased the population of 5-ethynyl-2'-deoxyuridine (EdU) or BrdU-labeled cells in the subventricular zone. Those RNase A-induced NPCs were able to migrate into other brain areas, including hippocampus, amygdala, cortex, striatum, and thalamus. In conclusion, our study shows that RNase A promotes proliferation of NPCs via an ERK-dependent pathway and further diversifies the physiological functions of the RNase A family.

Lonicera japonica extends lifespan and healthspan in Caenorhabditis elegans.

Lonicera japonica (LJ) is widely used as the local medicine to improve body and prevent ills in China, but mechanisms of its healthy beneficial effects remain largely unclear. Here, we evaluated the anti-aging and healthspan promoting activities of 75% ethanol extract of LJ (LJ-E) in the animal model Caenorhabditis elegans. Our results showed that LJ-E (500 µg/mL) treatment enhanced the mean lifespan of worms by over 21.87% and significantly improved age-associated physiological functions in C. elegans. The 500 µg/mL concentration of LJ-E enhanced the survival rates under oxidative and thermal stresses, and decreased reactive oxygen species (ROS) levels and fat accumulation in the worms. Gene-specific mutant studies showed that LJ-E-mediated lifespan extension was dependent on mev-1, daf-2, daf-16, and hsf-1, but not eat-2 genes. LJ-E could upregulate stress-inducible genes, viz., hsp-16.2, sod-3 and mtl-1. Moreover, we found that the D1086.10 protein interacted with superoxide dismutase (SOD)-3 by functional protein association networks analysis according to RNA-sequencing results. It was confirmed that D1086.10 was needed to promote longevity, and positively regulated expression of sod-3 by using D1086.10 mutants. Furthermore, LJ-E significantly delayed amyloid ß-protein induced paralysis in CL4176 strain. Given the important role of autophagy in aging and protein homeostasis, we observed that LJ-E could remarkably increase the mRNA expression of autophagy gene bec-1 in CL4176 strain, and decrease expression of autophagy substrate p62 protein by more than 40.0% in BC12921 strain. Finally, we found that combination composed of three major compounds (54 µg/mL chlorogenic acid, 15 µg/mL 1,5-dicaffeoylquinic acid and 7.5 µg/mL 1,3-dicaffeoylquinic acid) of 500 µg/mL LJ-E could significantly delay paralysis in CL4176 worms caused by Aß toxicity, comparable to that of LJ-E. Overall, our study may have important implications in using Lonicera japonica to promote healthy aging and have a potency to design therapeutics for age-related diseases.

Glycol chitin/PAA hydrogel composite incorporated bio-functionalized PLGA microspheres intended for sustained release of anticancer drug through intratumoral injection.

A novel anti-hepatoma drug release hybrid system is prepared by using poly(acrylic acid) (PAA) and glycol chitin as substrate in combination with Paclitaxel (PTX)-loaded bio-biofunctionalized poly(lactic-co-glycolic acid) (PLGA) micro-particles, which is intended for cancer therapy through intratumoral injection. The rheological behavior of glycol chitin (7 wt%)/PAA illustrates that it has low gelling temperature (i.e. 17 °C at pH 7.56) which ensures that the formulation turns to gel at physiological condition. The gelling time of glycol chitin/PAA is 16 minutes at 25 °C and 3 minutes at 37 °C, which is convenient for doctors to inject the in-situ gel formulations into the tumor location of patient. The drug release behavior reveals that the system can dramatically postpone the drug release. The cell viability test indicates that the micro-particles with drug still have 62% inhibitory effect on hepatoma cells in the fourteenth day after combing with hydrogel. This system is a promising approach for cancer therapy through intratumoral injection of in-situ gel formulations to extend retention time at tumor sites.

Echinacoside, a phenylethanoid glycoside from Cistanche deserticola, extends lifespan of Caenorhabditis elegans and protects from Aß-induced toxicity.

Cistanche deserticola has been found to exert protection against aging and age-related diseases, but mechanisms underlying its longevity effects remain largely unclear. Here, the multicellular model organism Caenorhabditis elegans was employed to identify lifespan extending and protective effects against ß-amyloid (Aß) induced toxicity by echinacoside (ECH), a phenylethanoid glycoside isolated from C. deserticola. Our results showed that ECH extends the mean lifespan of worms and increases their survival under oxidative stress. Levels of intracellular reactive oxygen species and fat accumulation were also significantly suppressed by ECH. Moreover, ECH-mediated lifespan extension was found to be dependent on mev-1, eat-2, daf-2, and daf-16, but not sir-2.1 or hsf-1 genes. Furthermore, ECH triggered DAF-16 nuclear localization and upregulated two of its downstream targets, sod-3 and hsp-16.2. In addition, ECH significantly improved the survival of CL4176 worms in response to proteotoxic stress induced by Aß protein aggregation. Collectively, these findings suggested that reactive oxygen species scavenging, dietary restriction, and insulin/insulin-like growth factor signaling pathways could be partly involved in ECH-mediated lifespan extension. Thus, ECH may target multiple longevity mechanisms to extend lifespan and have a potency to prevent Alzheimer's disease progression.

High strain-rate response of injectable PAA hydrogel.

Hydrogel materials have been widely considered as potential soft tissue replacements because of their high permeability, hydrophilicity, and biocompatibility, as well as their low coefficient of friction. Injectable (thermo-responsive) hydrogels can provide support and cushioning at irregularly shaped disease sites, and are thus suitable for use in treating osteoarthritis or degenerative disc disease. However, while some injectable hydrogels have been proven to sustain human body weight during daily activities, their mechanical properties under harsh dynamic conditions have not been well documented. A specified injectable polyacrylic acid (PAA) hydrogel was prepared for this study. To simulate sudden impacts or unexpected shocks to the PAA hydrogel, the split Hopkinson pressure bar technique was utilized. The dynamic responses of various hydrogels at confined high strain rates (100-2590 s(-1)) were presented. Hydrogel specimens with 3.37, 6.75, and 13.5% acrylic acid (AAc) concentrations were tested in the following three different material conditions: raw, phosphate-buffered saline (PBS) swollen, and PBS swollen with elevated temperature (37 °C). The dynamic bulk moduli of the hydrogels varied from 1.55 to 47.8 MPa depending on the given hydrogel's AAc concentration and swollen condition.

Stimulation of wound healing by PU/hydrogel composites containing fibroblast growth factor-2.

In this study, polyurethane (PU)/hydrogel composites were fabricated for wound healing applications. The hydrogel is a copolymer of thermosensitive N-isopropyl acrylamide (NIPAAm) and acrylic acid (AAc). γ-ray irradiation was employed to simultaneously copolymerize NIPAAm with AAc and graft the hydrogel onto porous PU. Fibroblast growth factor-2 (FGF-2) was incorporated into the composite to facilitate wound healing. The physical properties of the composites were characterized, the in vitro release of FGF-2 was examined, and in vivo tests were conducted. The results indicate that the thermosensitive hydrogel can absorb most of the wound exudates due to its high water uptake ability. Due to its thermosensitive properties, the PU/hydrogel composite is easier to strip off than that of commercial wound dressing, which prevents additional injury to the wound when replacing the wound dressing. In vivo results show that the PU/hydrogel composite incorporating FGF-2 could accelerate wound healing and reduce scar formation.

Poly(acrylic acid)-chitosan-silica hydrogels carrying platelet gels for bone defect repair.

Most hydrogels derived from either natural or synthetic sources suffer from the lack of mechanical strength. In this study, high strength poly(acrylic acid)-chitosan-silica (PAA-Ch-Si) hydrogels were prepared by UV polymerization for tissue engineering applications. Compressive strength up to 42 MPa can be achieved by the formation of an interpenetrating network (IPN) structure between PAA and chitosan with nano-silica as the filler. The preliminary cell culture of osteoblast cells (7F2) on PAA-Ch-Si hydrogels indicates good biological safety. The growth factor (platelet glue) is fast and completely released from PAA-Ch-Si hydrogel scaffolds within 620 min. The scaffold starts to degrade after eight months in vitro. Histological examinations demonstrate that the hydrogel incorporated with growth factors and osteoblast cells can promote cell migration. All these results illustrate that PAA-Ch-Si hydrogels are beneficial for tissue engineering applications and can be used as scaffolds for bone defect repair.

Atg9 interacts with dTRAF2/TRAF6 to regulate oxidative stress-induced JNK activation and autophagy induction.

Autophagy is a highly conserved catabolic process that degrades and recycles intracellular components through the lysosomes. Atg9 is the only integral membrane protein among autophagy-related (Atg) proteins thought to carry the membrane source for forming autophagosomes. Here we show that Drosophila Atg9 interacts with Drosophila tumor necrosis factor receptor-associated factor 2 (dTRAF2) to regulate the c-Jun N-terminal kinase (JNK) signaling pathway. Significantly, depletion of Atg9 and dTRAF2 compromised JNK-mediated intestinal stem cell proliferation and autophagy induction upon bacterial infection and oxidative stress stimulation. In mammalian cells, mAtg9 interacts with TRAF6, the homolog of dTRAF2, and plays an essential role in regulating oxidative stress-induced JNK activation. Moreover, we found that ROS-induced autophagy acts as a negative feedback regulator of JNK activity by dissociating Atg9/mAtg9 from dTRAF2/TRAF6 in Drosophila and mammalian cells, respectively. Our findings indicate a dual role for Atg9 in the regulation of JNK signaling and autophagy under oxidative stress conditions.

Novel pluronic-chitosan micelle as an ocular delivery system.

Pluronic micelles were prepared for ophthalmic delivery by incorporation of ethyl acetate as a dispersion agent and their surfaces were modified by chitosan to improve their bioavailability. The micelles disperse well in the solution and have a core-shell like structure with a particle size ranging from 93 to 181 nm for drug unloaded, 123-232 nm for drug-loaded, and a zeta potential between 6.1 and 9.2 mV, indicating very suitable use as ophthalmic carrier. The in vitro serum stability tests indicate the particle size of the micelles was very stable during the serum absorption. The turbidity test reveals that the prepared micelles were very stable under phosphate buffered saline environment, which can prevent the blurred vision. The loading efficiency of metipranolol in micelles can be as high as 83%. Finally, the in vitro and in vivo studies indicate the pluronic micelles modified by chitosan have sustained release behavior and good pharmacological response. As the results, the pluroic-chitosan micelles system provides a potential opportunity in decreasing frequency of administration and improving patient compliance for ocular drug delivery.

Evaluation of epirubicin in thermogelling and bioadhesive liquid and solid suppository formulations for rectal administration.

Temperature sensitive Pluronic (Plu) and pH-sensitive polyacrylic acid (PAA) were successfully mixed in different ratios to form in situ gelling formulations for colon cancer therapy. The major formulations were prepared as the liquid and solid suppository dosage forms. Epirubicin (Epi) was chosen as a model anticancer drug. In vitro characterization and in vivo pharmacokinetics and therapeutic efficacy of Epi in six Plu/PAA formulations were evaluated. Our in vitro data indicate that Epi in Plu 14%/PAA 0.75% of both solid and liquid suppositories possess significant cytotoxicity, strong bioadhesive force, long-term appropriate suppository base, sustained release, and high accumulation of Epi in rat rectums. These solid and liquid suppositories were retained in the upper rectum of Sprague-Dawley (SD) rats for at least 12 h. An in vivo pharmacokinetic study using SD rats showed that after rectal administration of solid and liquid suppositories, Epi had greater area under the curve and higher relative bioavailability than in a rectal solution. These solid and liquid suppositories exhibited remarkable inhibition on the tumor growth of CT26 bearing Balb/c mice in vivo. Our findings suggest that in situ thermogelling and mucoadhesive suppositories demonstrate a great potential as colon anticancer delivery systems for protracted release of chemotherapeutic agents.

pH-and thermo-sensitive pluronic/poly(acrylic acid) in situ hydrogels for sustained release of an anticancer drug.

In this study, we developed oral in situ gelling formulations composed of pluronic (Plu) and polyacrylic acid (PAA) for the delivery of an anticancer drug, epirubicin (Epi). We investigated various Plu/PAA/Epi formulations for their physicochemical properties and in vitro permeation and accumulation, as well as for in vivo pharmacokinetic and antitumor efficacy. A scanning electron microscopic (SEM) image of Plu 14%/PAA 0.75%/Epi hydrogel showed a sponge-like structure. This formulation has suitable gelation time, water content, bioadhesive force, structural stability, and a high permeation percentage of Epi, with sustained drug release characteristics for 96 h. This hydrogel was retained at the end of the ileum near the colon of Sprague-Dawley (SD) rats for at least 12 h. An in vivo pharmacokinetic study using SD rats showed that after oral administration in this formulation, Epi had prolonged half-life, greater area under the curve, and higher relative bioavailability than in an oral Epi solution. In vivo tumor growth inhibition of Epi in this formulation was more pronounced compared with oral Epi and intravenous Epi solutions in CT-26 mouse colon adenocarcinoma bearing Balb/c mice. This study highlights the advantages of using oral in situ temperature- and pH-sensitive hydrogels for future cancer therapy.

Post treatment of plasma-polymerized SnOx organic-like films with poly ethylene glycol for improving CO gas sensitivity.

In this study, a new room temperature type gas sensor device based on plasma deposition of tetramethyltin (TMT) and O2 organically hybridized film followed by post treatment on the deposited film was developed for improving CO gas sensitivity and distinguishing from methane, butane, and carbon monoxide gases in the test environment. Plasma deposited SnOx thin film was first produced from TMT and O2 gas mixtures at room temperature, and then post treatments on the SnOx thin films were carried out by either spin coating with poly ethylene glycol (PEG) or surface grafting with p-styrenesulfonic acid sodium salt (Nass). It was found that the gas sensor spin coating post treated with PEG exhibits linear response to CO gas with the sensitivity not affected by methane and butane gases. For CO concentrations ranging from 30 to 650 ppm, steep change in the sensor resistance can be detected without warming up the sensor.