Sustained release of 5-aminosalicylic acid from azoreductase-responsive polymeric prodrugs for prolonged colon-targeted colitis therapy.

Ulcerative colitis (UC) is a challenging inflammatory gastrointestinal disorder, whose therapies encounter limitations in overcoming insufficient colonic retention and rapid systemic clearance. In this study, we report an innovative polymeric prodrug nanoformulation for targeted UC treatment through sustained 5-aminosalicylic acid (5-ASA) delivery. Amphiphilic polymer-based 13.5 nm micelles were engineered to incorporate azo-linked 5-ASA prodrug motifs, enabling cleavage via colonic azoreductases. In vitro, micelles exhibited excellent stability under gastric/intestinal conditions while demonstrating controlled 5-ASA release over 24 h in colonic fluids. Orally administered micelles revealed prolonged 24-h retention and a high accumulation within inflamed murine colonic tissue. At an approximately 60% dose reduction from those most advanced recent studies, the platform halted DSS colitis progression and outperformed standard 5-ASA therapy through a 77-97% suppression of inflammatory markers. Histological analysis confirmed intact colon morphology and restored barrier protein expression. This integrated prodrug nanoformulation addresses limitations in colon-targeted UC therapy through localized bioactivation and tailored pharmacokinetics, suggesting the potential of nanotechnology-guided precision delivery to transform disease management.

The effect and mechanism of variable particle size microplastics and levofloxacin on the neurotoxicity of Rana nigromaculata based on the microorganism-intestine-brain axis.

Microplastics (MPs) usually appear in the aquatic environment as complex pollutants in combination with other environmental pollutants, such as levofloxacin (LVFX). After a 45-day exposure to LVFX and MPs with different particle sizes at environmental levels, LVFX was neurotoxic to Rana nigromaculata tadpoles. The order of the effects of the exposure treatment on tadpole behavior was: LVFX-MP3>LVFX-MP1>LVFX-MP2 ≥ LVFX. Results of transcriptome analysis of tadpole brain tissue showed that LVFX in combination with 0.10 and 10.00 µm MP interferes with the nervous system through the cell adhesion molecules pathway. Interestingly, the order of effects of the co-exposure on oxidative stress in the intestine was inconsistent with that of tadpole behavior. We found that Paraacteroides might be a microplastic indicator species for the gut microbiota of aquatic organisms. The results of the targeted metabolism of neurotransmitters in the intestine suggest that in the LVFX-MP2 treatment, LVFX alleviated the intestinal microbiota disorder caused by 1.00 µm MP, by regulating intestinal microbiota participating in the TCA cycle VI and gluconeogenesis and tetrapyrrole biosynthesis I, while downregulating Met and Orn, and upregulating 5HIAA, thereby easing the neurotoxicity to tadpoles exposed to LVFX-MP2. This work is of great significance for the comprehensive assessment of the aquatic ecological risks of microplastics-antibiotic compound pollutants.

The adsorption and its mechanism of venlafaxine by original and aged polypropylene microplastic and the changes of joint toxicity.

Conjugation with the increment of consumption of polypropylene (PP) masks and antidepressants during pandemic, PP microplastics (MPs) and Venlafaxine (VEN) widely co-existed in surface waters. However, their environmental fate and the combined toxicity were unclear. Hence, we investigated the adsorption behaviors, and associated mechanisms of PP MPs for VEN. The impact factors including pH, salinity, and MPs aging were estimated. The results indicated PP MPs could adsorb amount of VEN within 24 h. The pseudo second-order kinetic model (R2 = 0.97) and Dubinin-Radushkevich model (R2 = 0.89) fitted well with the adsorption capacity of PP MPs for VEN, implying that chemical adsorption accompanied by electrostatic interaction might be the predominant mode for the interactions between PP MPs and VEN. Meanwhile, the adsorption capacity of PP MPs declined from pH of 2.5-4.5 and then increased from 4.5 to 9.5. The increased salinity (5-35 ppt) significantly suppressed the adsorption capacity. Aging by sunlight and UV triggered the formation of new functional group (carbonyl) on MPs, and then enhanced the adsorption capacity for VEN. Gaussian Model analysis further evidenced the electrostatic adsorption occurring in PP MPs and VEN. The combined exposure to PP MPs and VEN showed significantly antagonistic toxicity on Daphnia magna. The adsorption of VEN by PP MPs mitigated the lethal effects and behavioral function impairment posed by VEN on animals, implying the potential protective effects on zooplankton by PP MPs. This study for the first time provides perspective for assessing the environmental fate of MPs and antidepressants in aquatic system.

Influences of ultrasound osteotome on wound infection and wound complications following removal of mandibular wisdom teeth.

We conducted this study to assess the effect of ultrasound osteotome on surgical site wound infection and pain following removal of mandibular wisdom teeth. A computerised search of Embase, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure databases for publicly available randomised controlled trials (RCTs) on the clinical effects of applying ultrasound osteotome to extract mandibular wisdom teeth was conducted from the inception of the databases to September 2023. Two researchers independently screened the retrieved results for literature screening, quality assessment and data extraction. RevMan 5.4 software was applied for data analysis. A total of 17 RCTs were included in this study, including 848 cases in the ultrasound osteotome group and 842 cases in the control group. The analysis revealed, compared with the control group, the ultrasound osteotome group showed a significantly lower incidence of postoperative wound infection (1.42% vs. 5.46%, odds ratio [OR]: 0.30, 95% confidence intervals [CI]: 0.17-0.53, p < 0.0001), fewer postoperative complications (6.35% vs. 22.12%, OR: 0.23, 95% CI: 0.17-0.32, p < 0.00001), shorter operative time (standardised mean differences [SMD]: -1.30, 95% CI: -1.97 to -0.64, p = 0.0001) and lower wound pain scores (SMD: -2.26 95% CI -2.80 to -1.73, p < 0.00001). Strong evidence suggests that ultrasound osteotome applied to extract mandibular wisdom teeth is more advantageous in terms of lower postoperative wound infection, less wound pain, fewer postoperative complications and shorter operative time compared with conventional treatment methods, but large-scale, multicentre RCTs are still needed to obtain more accurate results.

SHOU4/4L link cell wall cellulose synthesis to pattern-triggered immunity.

Pattern recognition receptors (PRRs) are plasma membrane-localised proteins that sense molecular patterns to initiate pattern-triggered immunity (PTI). Receptor-like cytoplasmic kinases (RLCKs) function downstream of PRRs to propagate signal transduction via the phosphorylation of substrate proteins. The identification and characterisation of RLCK-regulated substrate proteins are critical for our understanding of plant immunity. We showed that SHOU4 and SHOU4L are rapidly phosphorylated upon various patterns elicitation and are indispensable for plant resistance to bacterial and fungal pathogens. Protein-protein interaction and phosphoproteomic analysis revealed that BOTRYTIS-INDUCED KINASE 1, a prominent protein kinase of RLCK subfamily VII (RLCK-VII), interacted with SHOU4/4L and phosphorylated multiple serine residues on SHOU4L N-terminus upon pattern flg22 treatment. Neither phospho-dead nor phospho-mimic SHOU4L variants complemented pathogen resistance and plant development defect of the loss-of-function mutant, suggesting that reversible phosphorylation of SHOU4L is critical to plant immunity and plant development. Co-immunoprecipitation data revealed that flg22 induced SHOU4L dissociation from cellulose synthase 1 (CESA1) and that a phospho-mimic SHOU4L variant inhibited the interaction between SHOU4L and CESA1, indicating the link between SHOU4L-mediated cellulose synthesis and plant immunity. This study thus identified SHOU4/4L as new components of PTI and preliminarily revealed the mechanism governing SHOU4L regulation by RLCKs.

A high molecular weight silk fibroin scaffold that resists degradation and promotes cell proliferation.

The regulation of the biodegradation rate of 3D-regenerated silk fibroin scaffolds and the avoidance of premature collapse are important concerns for their effective applications in tissue engineering. In this study, bromelain, which is specific to sericin, was used to remove sericin from silk, and high molecular weight silk fibroin was obtained after the fibroin fibers were dissolved. Afterwards, a 3D scaffold was prepared via freeze-drying. The Sodium dodecyl sulfate-polyacrylamide gel electrophoresis results showed that the average molecular weight of the regenerated silk fibroin prepared by using the bromelain-degumming method was approximately 142.2 kDa, which was significantly higher than that of the control groups prepared by using the urea- and Na2 CO3 -degumming methods. The results of enzyme degradation in vitro showed that the biodegradation rate and internal three-dimensional structure collapse of the bromelain-degumming fibroin scaffolds were significantly slower than those of the two control scaffolds. The proliferation activity of human umbilical vein vascular endothelial cells inoculated in bromelain-degumming fibroin scaffolds was significantly higher than that of the control scaffolds. This study provides a novel preparation method for 3D-regenerated silk fibroin scaffolds that can effectively resist biodegradation, continuously guide cell growth, have good biocompatibility, and have the potential to be used for the regeneration of various connective tissues.

Simultaneous Imaging and Photodynamic-Enhanced Photothermal Inhibition of Cancer Cells Using a Multifunctional System Combining Indocyanine Green and Polydopamine-Preloaded Upconversion Luminescent Nanoparticles.

This work introduces a novel multifunctional system called UPIPF (upconversion-polydopamine-indocyanine-polyethylene-folic) for upconversion luminescent (UCL) imaging of cancer cells using near-infrared (NIR) illumination. The system demonstrates efficient inhibition of human hepatoma (HepG2) cancer cells through a combination of NIR-triggered photodynamic therapy (PDT) and enhanced photothermal therapy (PTT). Initially, upconversion nanoparticles (UCNP) are synthesized using a simple thermal decomposition method. To improve their biocompatibility and aqueous dispersibility, polydopamine (PDA) is introduced to the UCNP via a ligand exchange technique. Indocyanine green (ICG) molecules are electrostatically attached to the surface of the UCNP-polydopamine (UCNP@PDAs) complex to enhance the PDT and PTT effects. Moreover, polyethylene glycol (PEG)-modified folic acid (FA) is incorporated into the UCNP-polydopamine-indocyanine-green (UCNP@PDA-ICGs) nanoparticles to enhance their targeting capability against cancer cells. The excellent UCL properties of these UCNP enable the final UCNP@PDA-ICG-PEG-FA nanoparticles (referred to as UPIPF) to serve as a potential candidate for efficient anticancer drug delivery, real-time imaging, and early diagnosis of cancer cells. Furthermore, the UPIPF system exhibits PDT-assisted PTT effects, providing a convenient approach for efficient cancer cell inhibition (more than 99% of cells are killed). The prepared UPIPF system shows promise for early diagnosis and simultaneous treatment of malignant cancers.

Effects of Microplastic (MP) Exposure at Environmentally Relevant Doses on the Structure, Function, and Transcriptome of the Kidney in Mice.

As a common emerging environmental pollutant, microplastics (MPs) have been detected in a variety of environmental media and human bodies. The potential toxic effects and mechanisms of MPs need to be revealed urgently. MPs can be deposited in the kidney, and exposure to high doses of MPs can cause nephrotoxicity in experimental animals. In this study, we investigated the effects of exposure to polystyrene microplastics (PS-MPs) at environmentally relevant doses (0.1 and 1 mg/L) on kidney structure, function, and transcriptome in mice. We found that mice exposed to PS-MPs in drinking water for eight weeks had no change in body weight or kidney coefficient. PS-MPs administration decreased the levels of blood urea nitrogen (BUN) in mice, while serum creatinine (CRE) and uric acid (UA) concentrations were unaffected. Through using periodic acid-Schiff (PAS) and Masson staining, we discovered that the glomerular tuft area increased in the PS-MP-treated mice, while the degree of renal fibrosis remained unchanged. Furthermore, renal cortex transcriptomic analysis identified 388 and 303 differentially expressed genes (DEGs) in the 0.1 and 1 mg/L dose groups, respectively. The DEGs were highly enriched in mitochondrial-related terms and pathways of thermogenesis and oxidative phosphorylation. Moreover, protein-protein interaction (PPI) network analysis revealed that cytochrome b-c1 complex subunit 10 (UQCR11) and cytochrome c oxidase subunit 3 (MT-CO3) were important node proteins. These findings suggest that environmental exposure to MPs can cause abnormalities in renal structure and filtration function and that long-term exposure to MPs may be a risk factor for renal disease.

Identification of WxL and S-Layer Proteins from Lactobacillus brevis with the Ability to Bind Cellulose and Xylan.

Xylanase releases xylo-oligosaccharides from dietary xylan, which stimulate the growth of the gut bacteria lactobacilli. Many lactobacilli adhere to dietary fibers, which may facilitate the assimilation of xylo-oligosaccharides and help them gain competence in the gut, but the underlying mechanisms remain elusive. Herein we report, from the highly abundant transcripts of Lactobacillus brevis cultured in wheat arabinoxylan supplemented with a xylanase, the identification of genes encoding four putative cell-surface WxL proteins (Lb630, Lb631, Lb632, and Lb635) and one S-layer protein (Lb1325) with either cellulose- or xylan-binding ability. The repetitively occurring WxL proteins were encoded by a gene cluster, among which Lb630 was chosen for further mutational studies. The analysis revealed three aromatic residues (F30, W61, and W156) that might be involved in the interaction of the protein with cellulose. A homology search in the genome of Enterococcus faecium identified three WxL proteins with conserved counterparts of these three aromatic residues, and they were also found to be able to bind cellulose and xylan. The findings suggested a role of the cell-surface WxL and S-layer proteins in assisting the cellular adhesion of L. brevis to plant cell wall polysaccharides.

Construction and Biological Evaluation of Multiple Modification Hollow Mesoporous Silicone Doxorubicin Nanodrug Delivery System.

The combination of functionalized nanoparticles and chemotherapy drugs can effectively target tumor tissue, which can improve efficacy and reduce toxicity. In this article, pPeptide-PDA@HMONs-DOX nanoparticles (phosphopeptide-modified polydopamine encapsulates doxorubicin-loaded hollow mesoporous organosilica nanoparticles) were constructed that based on multiple modification hollow mesoporous organosilica nanoparticles (HMONs). The pPeptide-PDA@HMONs-DOX nanoparticles retain the biological functions of phosphorylated peptide while exhibiting biological safety that are suitable for effective drug delivery and stimulus responsive release. The degradation behaviors showed that pPeptide-PDA@HMONs-DOX has dual-responsive to drug release characteristics of pH and glutathione (GSH). In addition, the prepared pPeptide-PDA@HMONs-DOX nanoparticles have good biological safety, and their anti-tumor efficacy was significantly better than doxorubicin (DOX). This provided new research ideas for the construction of targeted nanodrug delivery systems based on mesoporous silicon. Scheme 1 The preparation of pPeptide-PDA@HMONs-DOX and the process of drug release under multiple responses. (A) Schematic diagram of the synthesis process of pPeptide-PDA@HMONs-DOX. (B) The process in which nanoparticles enter the cell and decompose and release DOX in response to pH and GSH.

Analyses of key mRNAs and lncRNAs for different osteo-differentiation potentials of periodontal ligament stem cell and gingival mesenchymal stem cell.

Both human periodontal ligament stem cells (hPDLSCs) and human gingival mesenchymal stem cells (hGMSCs) are candidate seed cells for bone tissue engineering, but the osteo-differentiation ability of the latter is weaker than the former, and the mechanisms are unknown. To explore the potential regulation of mRNAs and long non-coding RNAs (lncRNAs), this study obtained the gene expression profiles of hPDLSCs and hGMSCs in both undifferentiated and osteo-differentiated conditions by microarray assay and then analysed the common and specific differentially expressed mRNAs and lncRNAs in hPDLSCs and hGMSCs through bioinformatics method. The results showed that 275 mRNAs and 126 lncRNAs displayed similar changing patterns in hPDLSCs and hGMSCs after osteogenic induction, which may regulate the osteo-differentiation in both types of cells. In addition, the expression of 223 mRNAs and 238 lncRNAs altered only in hPDLSCs after osteogenic induction, and 177 mRNAs and 170 lncRNAs changed only in hGMSCs. These cell-specific differentially expressed mRNAs and lncRNAs could underlie the different osteo-differentiation potentials of hPDLSCs and hGMSCs. Finally, dickkopf Wnt signalling pathway inhibitor 1 (DKK1) was proved to be one regulator for the weaker osteo-differentiation ability of hGMSCs through validation experiments. We hope these results help to reveal new mRNAs-lncRNAs-based molecular mechanism for osteo-differentiation of hPDLSCs and hGMSCs and provide clues on strategies for improving stem cell-mediated bone regeneration.

Microplastic Pollution in Nearshore Sediment from the Bohai Sea Coastline.

Microplastics are recognized as an emerging global issue in marine environments. In this study, microplastic pollution in subtidal sediments from nine typical stations in the Bohai Sea was investigated. The mean concentration was 458.6 ± 150.0 items/kg of dry weight, varying from 280.0 to 773.4 items/kg. All of the microplastics were categorized according to shape, color and size. Among these microplastics, fiber (77.1%), white/blue/black (85.0%) and small microplastics (< 1500 µm) (82.9%) were the most abundant types. Seven polymer types were identified and were, in decreasing order of abundance, rayon > PE > PS > PP > PET > ABS > PA. The microplastics abundance was of the same order of magnitude as that of other similar areas. The microplastic characteristics suggest that tourism, maritime activities and sewage discharge are possible sources. Our results provide useful information for performing an environmental risk assessment of microplastic pollution in this area.

Dimeric small molecule agonists of EphA2 receptor inhibit glioblastoma cell growth.

EphA2 receptor kinase could become a novel target for anti-glioblastoma treatment. Doxazosin previously identified acts like the endogenous ligand of EphA2 and induces cell apoptosis. Through lead structure modification a derivative of Doxazosin possessing unique dimeric structure showed an improvement in the activity. In the current study, we expanded the dimeric scaffold by lead optimization to explore the chemical space of the conjoining moieties and a slight variation to the core structure. 27 new derivatives were synthesized and examined with EphA2 overexpressed and wild type glioblastoma cell lines for cell proliferation and EphA2 activation. Three new compounds 3d, 3e, and 7bg showed potent and selective activities against the growth of EphA2 overexpressed glioblastoma cells. Dimer 3d modification replaces the long alkyl chain with a short polyethylene glycol chain. Dimer 7bg has a relatively longer polyethylene glycol chain in comparison to compound 3d and the length is more similar to the lead compound. Whereas dimer 3e has a rigid aromatic linker exploring the chemical space. The diversity of the linkers in the active suggest additional hydrogen binding sites has a positive correlation to the activity. All three dimers showed selective activity in EphA2 overexpressed cells, indicating the activity is correlated to the EphA2 targeting effect.

Pathologic evaluation of the solid variant of aneurysmal bone cysts with USP6 rearrangement with an emphasis on the frequent diagnostic pitfalls.

The solid variant of aneurysmal bone cyst (SVABC) is very uncommon and frequently misdiagnosed. We reevaluated and summarized the clinicopathologic features of 17 SVABCs and further discussed the use of this nomenclature to differ SVABCs from extragnathic giant cell reparative granuloma (GCRG) in the setting of the USP6 rearrangement era. The immunohistochemical markers included α-SMA, SATB2, AE1/AE3, Ki67, S100, CD68 and P63. USP-6 status was detected by fluorescence in situ hybridization using a break-apart probe. The 17 patients with SVABCs comprised 10 males and 7 females ranging in age from 4 to 70 years. The involved locations included the long bone (n = 11), hand (n = 4), rib (n = 1) and vertebra (n = 1). The lesions were characterized by proliferated spindle cells with scattered giant cells and hemorrhages with variable positive α-SMA, SATB2, CD68 and Ki-67 expression. All patients had USP6 rearrangements without H3F3A glycine 34 mutations. Our study reveals that SVABC shares similar clinical and histologic features with other bone lesions, which may lead to an erroneous diagnosis. The presence of an USP-6 rearrangement contributes to the diagnosis SVABC; SVABC and most of the previously documented extragnathic GCRGs may be considered within the umbrella of primary aneurysmal bone cysts.

Evaluation of the Genotoxic and Oxidative Damage Potential of Silver Nanoparticles in Human NCM460 and HCT116 Cells.

Nano Ag has excellent antibacterial properties and is widely used in various antibacterial materials, such as antibacterial medicine and medical devices, food packaging materials and antibacterial textiles. Despite the many benefits of nano-Ag, more and more research indicates that it may have potential biotoxic effects. Studies have shown that people who ingest nanoparticles by mouth have the highest uptake in the intestinal tract, and that the colon area is the most vulnerable to damage and causes the disease. In this study, we examined the toxic effects of different concentrations of Ag-NPs on normal human colon cells (NCM460) and human colon cancer cells (HCT116). As the concentration of nanoparticles increased, the activity of the two colon cells decreased and intracellular reactive oxygen species (ROS) increased. RT-qPCR and Western-blot analyses showed that Ag NPs can promote the increase in P38 protein phosphorylation levels in two colon cells and promote the expression of P53 and Bax. The analysis also showed that Ag NPs can promote the down-regulation of Bcl-2, leading to an increased Bax / Bcl-2 ratio and activation of P21, further accelerating cell death .This study showed that a low concentration of nano Ag has no obvious toxic effect on colon cells, while nano Ag with concentrations higher than 15 µg/mL will cause oxidative damage to colon cells.

Impact of Antifouling PEG Layer on the Performance of Functional Peptides in Regulating Cell Behaviors.

Cell adhesive and other functional peptides (such as RGD, KRSR, YIGSR, VAPG, and BMP-2 peptides) are extensively studied and utilized in tissue engineering scaffolds and biomedical devices to modulate cell functions. Though PEG is frequently used as the antifouling layer, it is unclear how it affects the performance of functional peptides. By analyzing the impact of PEG at short (OEG4), medium (OEG8), and long chain length (PEG2K), we reveal that PEG chain length is critical and a medium-length PEG enables functional peptides to display their optimal and genuine functions in cell adhesion, migration, and differentiation by providing excellent antifouling to minimize background noise of unwanted cell adhesion and high enough surface density of functional peptides. Our result provides new avenues for maximizing the genuine functions of peptides. This study also provides a solution to prevent the heterogeneous and even divergent results caused by inappropriate choice of antifouling PEG and provides a general guidance in identifying new functional peptides.

Drag-reducing polymers increase exercise tolerance in an ischemic hind-limb rat model.

OBJECTIVE: Drag-reducing polymers are long-chain, blood soluble macromolecules that can improve microcirculation in vivo. This study aimed to examine the effects of drag-reducing polymers on exercise tolerance in a rat model of hind-limb ischemia. METHODS: After adaptive running training, bilateral femoral artery ligation models were established in 64 Wistar rats. During an exhaustive exercise, polyethylene oxide or normal saline was intravenously injected to each group (n = 32) at 4 mL/h for 10 min. The exhaustive exercise time was recorded, and lactic acid levels in gastrocnemius muscle and serum were measured. Serum levels of nitric oxide, creatine kinase and lactate dehydrogenase were measured as biomarkers of physical fatigue. RESULTS: Compared with saline-treated control group, rats in polyethylene oxide-treated group had longer exhaustive exercise time (774.7 ± 171.5 s vs. 687.6 ± 166.1 s, p = 0.043), and lower lactic acid level in gastrocnemius muscle (p < 0.01) but no significant difference in serum lactic acid level between two groups was observed (p > 0.05). Nitric oxide level was higher in polyethylene oxide group than in controls (p < 0.05), but no significant differences in serum creatine kinase and lactate dehydrogenase levels between two groups were observed (p > 0.05). CONCLUSION: Drag-reducing polymers contribute to the enhancement of exercise endurance and exert anti-fatigue effect.

Self-Assembled Cubic Liquid Crystalline Nanoparticles for Transdermal Delivery of Paeonol.

BACKGROUND: The aim of this study was to optimize the preparation method for self-assembled glyceryl monoolein-based cubosomes containing paeonol and to characterize the properties of this transdermal delivery system to improve the drug penetration ability in the skin. MATERIAL AND METHODS: In this study, the cubic liquid crystalline nanoparticles loaded with paeonol were prepared by fragmentation of glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel by high-pressure homogenization. We evaluated the Zeta potential of these promising skin-targeting drug-delivery systems using the Malvern Zeta sizer examination, and various microscopies and differential scanning calorimetry were also used for property investigation. Stimulating studies were evaluated based on the skin irritation reaction score standard and the skin stimulus intensity evaluation standard for paeonol cubosomes when compared with commercial paeonol ointment. In vitro tests were performed on excised rat skins in an improved Franz diffusion apparatus. The amount of paeonol over time in the in vitro penetration and retention experiments both was determined quantitatively by HPLC. RESULTS: Stimulating studies were compared with the commercial ointment which indicated that the paeonol cubic liquid crystalline nanoparticles could reduce the irritation in the skin stimulating test. Thus, based on the attractive characteristics of the cubic crystal system of paeonol, we will further exploit the cosmetic features in the future studies. CONCLUSIONS: The transdermal delivery system of paeonol with low-irritation based on the self-assembled cubic liquid crystalline nanoparticles prepared in this study might be a promising system of good tropical preparation for skin application.

Antiviral effects of two Ganoderma lucidum triterpenoids against enterovirus 71 infection.

Enterovirus 71 (EV71) is a major causative agent for hand, foot and mouth disease (HFMD), and fatal neurological and systemic complications in children. However, there is currently no clinical approved antiviral drug available for the prevention and treatment of the viral infection. Here, we evaluated the antiviral activities of two Ganoderma lucidum triterpenoids (GLTs), Lanosta-7,9(11),24-trien-3-one,15;26-dihydroxy (GLTA) and Ganoderic acid Y (GLTB), against EV71 infection. The results showed that the two natural compounds display significant anti-EV71 activities without cytotoxicity in human rhabdomyosarcoma (RD) cells as evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay. The mechanisms by which the two compounds affect EV71 infection were further elucidated by three action modes using Ribavirin, a common antiviral drug, as a positive control. The results suggested that GLTA and GLTB prevent EV71 infection through interacting with the viral particle to block the adsorption of virus to the cells. In addition, the interactions between EV71 virion and the compounds were predicated by computer molecular docking, which illustrated that GLTA and GLTB may bind to the viral capsid protein at a hydrophobic pocket (F site), and thus may block uncoating of EV71. Moreover, we demonstrated that GLTA and GLTB significantly inhibit the replication of the viral RNA (vRNA) of EV71 replication through blocking EV71 uncoating. Thus, GLTA and GLTB may represent two potential therapeutic agents to control and treat EV71 infection.

Preparation and application of the thermo-/pH-/ ion-sensitive semi-IPN hydrogel based on chitosan.

Chitosan based hydrogels with multiple stimulus responses have broad application prospects in many fields. Considering the advantages of semi interpenetrating network (IPN) technology and the special temperature and ion responsiveness of polymers containing zwitterionic groups, a semi-IPN hydrogel was prepared through in situ free radical polymerization of N,N-dimethyl acrylamide and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide with polyethylene glycol dimethacrylate as a crosslinker and carboxymethyl chitosan as filler. The gel mass fraction and swelling ratio were measured, and the preparation conditions were optimized. The result indicated that the hydrogel possessed a unique thermo-/pH-/ ion-sensitive behavior. The swelling ratio increased with the increase of temperature and ion concentration, and showed a decreasing trend with the increase in pH. In addition, the hydrogel was stable when the stimuli changed. Adsorption behavior of the hydrogel to Eosin Y (EY) was systematically investigated. The adsorption process can be described well by the pseudo-second-order kinetic model and Langmuir isotherm model, indicating that it was a chemical adsorption. The experiments indicated that the hydrogel exhibited good antifouling and reusability features. Therefore, the semi-IPN hydrogel with antifouling properties and thermo-/pH-/ion-sensitivity can be easily manufactured is expected to find applications in water treatment fields.