Competitive and cooperative sorption between triclosan and methyl triclosan on microplastics and soil.

The sorption behavior of single contaminant on microplastics (MPs) has been extensively studied; however, little is known about that in the more actual scenario containing multiple contaminants. In this study, the interaction between triclosan (TCS) and its primary metabolite, methyl triclosan (MTCS) on polyethylene (PE), polystyrene (PS), and soil was investigated. Results indicate that the more hydrophobic MTCS had much higher sorption capacity and affinity than TCS. Competitive sorption between them occurred in most cases and appeared to be concentration-dependent (in the range of 0.1-5 mg TCS/L and 0.01-≤0.05 mg MTCS/L of primary solutes, respectively): more pronounced at low concentrations of primary solute, while progressively weaker with the increase of concentrations. Among the sorbents, MTCS exhibited strong antagonistic effect on TCS sorption for MPs, especially PS, while significant suppression of MTCS sorption by TCS took place for soil and PS rather than PE. Additionally, it is interesting to observe that the presence of TCS substantially facilitated the sorption of MTCS exclusively at high concentrations on both PS and soil, presumably attributed to the solute-multilayer formation. Furthermore, the magnitude of the two effects varied with solution pH: TCS sorption at alkaline pH was the most suppressed by MTCS because the less hydrophobic dissociated TCS tended to be displaced, and the highest cooperative sorption of MTCS with TCS occurred at acidic pH because neutral TCS preferentially adsorbed on sorbent surface could provide additional sorption sites for MTCS. Both competitive and cooperative effects between multiple contaminants may affect their fate and transport, thereby these findings are helpful for assessing the environmental risk of MPs and TCS in soil.

Translocation of a looped polymer threading through a nanopore.

Recent experiments reported that the complicated translocation dynamics of a looped DNA chain through a nanopore can be detected by ionic current blockade profiles. Inspired by the experimental results, we systematically study the translocation dynamics of a looped polymer, formed by three building blocks of a loop in the middle and two tails of the same length connected with the loop, by using Langevin dynamics simulations. Based on two entering modes (tail-leading and loop-leading) and three translocation orders (loop-tail-tail, tail-loop-tail, and tail-tail-loop), the translocation of the looped polymer is classified into six translocation pathways, corresponding to different current blockade profiles. The probabilities of the six translocation pathways are dependent on the loop length, polymer length, and pore radius. Moreover, the translocation times of the entire polymer and the loop are investigated. We find that the two translocation times show different dependencies on the translocation pathways and on the lengths of the loop and the entire polymer.

Study of biodegradable occluder of atrial septal defect in a porcine model.

OBJECTIVE: To evaluate the safety and feasibility of a modified poly(l-lactic acid) (PLLA) atrial septal defect (ASD) occluder. METHODS: Forty-five piglets were divided into two groups: an experimental group (n = 27) and a control group (n = 18). The experimental group underwent percutaneous implantation of a modified PLLA ASD device while the control group underwent percutaneous implantation of a widely used metal ASD device. X-ray imaging, transthoracic echocardiography (TTE), electrocardiogram (ECG), histopathology and electron microscopic examination were performed at 7 days, 1, 3, 6, and 12 months after implantation. RESULTS: Twenty-seven experimental piglets and 18 control piglets were all successfully implanted with modified biodegradable and metal ASD devices, respectively. While both devices exhibited very good occluding effects, the modified PLLA ASD devices were completely endothelialized at 3 months after implantation, and the endothelialization appeared to be more complete compared to the control group. Degradation of the PLLA devices was noted at 12 months follow-up with no loss of integrity at the atrial septum. CONCLUSION: This animal model with implanting of the occluders was effective and not associated with complications. The modified PLLA ASD devices are more controllable and practical than our previous devices. The implanted devices demonstrated good endothelialization and degradability in short and moderate term follow-up. Long-term studies are now underway to further evaluate the biodegradability of this novel device.

A Method to Generate and Analyze Modified Myristoylated Proteins.

Covalent lipid modification of proteins is essential to their cellular localizations and functions. Engineered lipid motifs, coupled with bio-orthogonal chemistry, have been utilized to identify myristoylated or palmitoylated proteins in cells. However, whether modified proteins have similar properties as endogenous ones has not been well investigated mainly due to lack of methods to generate and analyze purified proteins. We have developed a method that utilizes metabolic interference and mass spectrometry to produce and analyze modified, myristoylated small GTPase ADP-ribosylation factor 1 (Arf1). The capacities of these recombinant proteins to bind liposomes and load and hydrolyze GTP were measured and compared with the unmodified myristoylated Arf1. The ketone-modified myristoylated Arf1 could be further labeled by fluorophore-coupled hydrazine and subsequently visualized through fluorescence imaging. This methodology provides an effective model system to characterize lipid-modified proteins with additional functions before applying them to cellular systems.

A General Strategy for Ligand Exchange on Upconversion Nanoparticles.

Lanthanide-doped upconversion nanoparticles with a suitable surface coating are appealing for biomedical applications. Because high-quality upconversion nanoparticles are typically prepared in an organic solvent and passivated by hydrophobic oleate ligands, a convenient and reliable method for the surface modification of upconversion nanoparticles is thus highly desired to satisfy downstream biological investigations. In this work, we describe a facile and versatile strategy for displacing native oleate ligands on upconversion nanoparticles with a diversity of hydrophilic molecules. The ligand-exchange procedure involves the removal of original oleate ligands followed by the attachment of new ligands in a separate step. The successful coating of relevant ligands was confirmed by Fourier transform infrared spectroscopy, thermogravimetry analysis, and ζ-potential measurement. The surface-modified nanoparticles display high stability and good biocompatibility, as revealed by electron microscopy, photoluminescence spectroscopy, and cytotoxicity assessment. Our study demonstrates that functional biomolecules such as biotin can be directly immobilized on the nanoparticle surface using this approach for the quick and effective detection of streptavidin.

A Novel-Design Poly-L-Lactic Acid Biodegradable Device for Closure of Atrial Septal Defect: Long-Term Results in Swine.

OBJECTIVES: The aim of this study is to evaluate the long-term effectiveness and safety of a self-expandable, double-disk biodegradable device made of poly-L-lactic acid (PLLA) for closure of atrial septal defects (ASDs) in swine. METHODS: ASDs were created by transseptal needle puncture followed by balloon dilatation in 20 piglets. The experimental group comprised 18 animals, while the remaining 2 animals were used as controls. Effectiveness and safety were evaluated by rectal temperature, leukocyte count, chest radiography, electrocardiogram, transthoracic echocardiography (TTE), intracardiac echocardiography (ICE), and histologic studies. Animals were followed up at 1, 3, 6, and 12 months. RESULTS: An ASD model was successfully created in 19 animals; 1 piglet died during the procedure. The ASD diameters that were created ranged from 5 to 6.4 mm. Devices were successfully implanted in 17 animals. No animal died during the follow-up studies. Rectal temperatures and electrocardiograms were normal at follow-up, while leukocyte counts transiently increased from 1 to 6 months. Radiography, TTE, ICE, and macroscopic studies demonstrated that PLLA occluders were positioned well, with no shifting, mural thrombus formation, or atrioventricular valve insufficiency. Histologic evaluations showed that PLLA devices were partially degraded in the follow-up study. CONCLUSIONS: ASD closure with the novel PLLA biodegradable device is safe and effective. Longer-term studies are needed to evaluate long-term biodegradability.

Characteristics and mechanisms of acrylate polymer damage to maize seedlings.

Superabsorbent acrylate polymers (SAPs) have been widely used to maintain soil moisture in agricultural management, but they may cause damage to plants, and the mechanisms are not well understood. In this study, seed germination, soil pot culture, hydroponic experiments, and SAPs degradation were conducted to investigate damage characteristics and mechanisms associated with SAPs application. The Results showed that SAPs inhibited maize growth and altered root morphology (irregular and loose arrangement of cells and breakage of cortex parenchyma), and the inhibitory effects were enhanced at higher SAPs rates. After 1h SAP hydrogels treatment, root malondialdehyde (MDA) content was significantly increased, while superoxide dismutase (SOD) and catalase (CAT) content were significantly decreased. Hydroponics experiment indicated that root and shoot growth was inhibited at 2.5mgL(-1) acrylic acid (AA), and the inhibition was enhanced with increasing AA rates. This effect was exacerbated by the presence of Na(+) at a high concentration in the hydrogels. Release and degradation of AA were enhanced at higher soil moisture levels. A complete degradation of AA occurred between 15 and 20 days after incubation (DAI), but it took longer for Na(+) concentration to decrease to a safe level. These results indicate that high concentration of both AA and Na(+) present in the SAPs inhibits plant growth. The finding of this study may provide a guideline for appropriate application of SAPs in agriculture.

[Stabilized thiomer PAA-Cys-6MNA].

The aimed of this study was to prepare stabilized thiomers to overcome the poor stability character of traditional thiomers. Poly(acrylic acid)-cysteine (PAA-Cys) was synthesized by conjugating cysteine with poly(acrylic acid) and poly(acrylic acid)-cysteine-6-mercaptonicotinic acid (PAA-Cys-6MNA, stabilized thiomers) was synthesized by grafting a protecting group 6-mercaptonicotinic acid (6MNA) with PAA-Cys. The free thiol of PAA-Cys was determined by Ellmann's reagent method and the ratio of 6MNA coupled was determined by glutathione reduction method. The study of permeation enhancement and stabilized function was conducted by using Franz diffusion cell method, with fluorescein isothiocyanate dextran (FD4) used as model drug. The influence of polymers on tight junctions of Caco-2 cell monolayer was detected with laser scanning confocal fluorescence microscope. The results indicated that both PAA-Cys and PAA-Cys-6MNA could promote the permeation of FD4 across excised rat intestine, and the permeation function of PAA-Cys-6MNA was not influence by the pH of the storage environment and the oxidation of air after the protecting group 6MNA was grafted. The distribution of tight junction protein of Caco-2 cell monolayer F-actin was influenced after incubation with PAA-Cys and PAA-Cys-6MNA. In conclusion, stabilized thiomers (PAA-Cys-6MNA) maintained the permeation function compared with the traditional thiomers (PAA-Cys) and its stability was improved. The mechanism of the permeation enhancement function of the polymers might be related to their influence on tight junction relating proteins of cells.

Efficient direct preparation of antifungal Alteramide B from Lysobacter enzymogenes fermentation broth by macroporous resin adsorption.

Alteramide B (ATB) is an antifungal metabolite produced by Lysobacter enzymogenes. However, its separation method has not been explored. This study attempted to directly adsorb ATB from fermentation broth using macroporous adsorption resins (MARs) NKA resin exhibited better adsorption as well as desorption capacities. The static and dynamic adsorption characteristics were assessed to determine the following optimal separation conditions: initial fermentation broth with a pH of 12.0, 2 BV/h flow rate, 8 BV loading volume, and 6 BV 80% aqueous ethanol for elution. After a single treatment, ATB content in the final product was higher by 4.51-fold (i.e, from 12.72 ± 1.21% to 57.35 ± 3.46%), resulting in a recovery yield of 86.20 ± 4.47%. In addition, NKA resin showed superior reusability within eight cycles of adsorption/desorption. The developed method is thus a simple, efficient, and economical process for ATB separation.

Comparison of adsorption and desorption of triclosan between microplastics and soil particles.

Microplastic (MP) pollution in soil has been becoming an emerging environmental hot spot, but little is known about the interaction between MPs and chemical contaminants in soil. In this study, batch experiments were performed to study adsorption-desorption behavior and mechanism of triclosan (TCS) on MPs, polyethylene (PE) and polystyrene (PS), and soil particles. PE showed the highest adsorption rate (29.3 mg µg-1 h-1) and equilibrium capacity (1248 µg g-1), while the similar profiles between PS (0.27 mg µg-1 h-1 and 1033 µg g-1, respectively) and soil (0.60 mg µg-1 h-1 and 961 µg g-1, respectively). Two adsorption stages, representing liquid-film and intra-particle diffusion were observed obviously for PE. Adsorption isotherm results revealed that the interaction between MPs and TCS was relatively weak. The sorption potential of soil was lower than that of MPs especially at high concentrations. PE addition induced TCS sorption increase in soil, while PS had no significant (P > 0.05) influence. For MP-soil systems, TCS preferred to adsorb on MPs, which was more pronounced for PE than PS. The desorption rate of TCS was the highest for soil, followed by PE and PS, while equilibrium release amount ranked: PE > PS > soil. Moreover, soil solution better facilitated the desorption, with the amount increasing by 38% for PE compared with 0.01 M CaCl2 solution. Therefore, MPs, especially PE with high adsorption and desorption potentials may serve as a source and carrier to TCS, and its amendment can change TCS environmental behavior and further risk in soil.

Cephalometric craniofacial features of patients with Sagliker syndrome: a primary analysis of our experience.

BACKGROUND: Sagliker syndrome (SS) is characterized by a severe uglifying facial appearance resulting from untreated or inadequately treated secondary hyperparathyroidism (SHPT). To date, the craniofacial morphology of patients with SS has yet to be analyzed. The present research sought to cephalometrically evaluate the craniofacial features of patients with SS and to perform an in-depth analysis of their serum biochemical parameters, with the aim of furthering the theoretical basis for the early diagnosis and prevention of SS. METHODS: A retrospective chart review of 9 patients who fulfilled the diagnostic criteria for SS were included in this study, and their serum biochemical parameters were collected. After subjecting standard lateral cephalometric radiographic images to correction for distortions caused by magnification followed by digitization, we conducted a cephalometric analysis. Student's two-tailed t tests or Mann-Whitney U tests were used to analyze the data. Thirty-three patients with patients with SHPT alone were also included as controls. RESULTS: The lower anterior facial height (ANS-ME) and total anterior facial height (N-Me) measurements of patients with SS were significantly increased compared to those of the controls. The angles between the Frankfort horizontal, palatal, and occlusal planes and the mandibular plane, were greater in the SS group than in the control group, as was the gonial angle. Patients with SS also exhibited a significantly larger maxillary protrusion angle and relative position of the maxilla to the mandible. Most patients with SS had class II malocclusion, whereas most of the controls exhibited normal occlusion. Soft tissue largely followed the same pattern as craniofacial changes. Our investigation also showed that among patients with SHPT, female sex, longer duration of dialysis, and higher serum levels of alkaline phosphatase and intact parathyroid hormone were associated with development to SS. CONCLUSIONS: Patients with SS show facial and biochemical differences compared to patients with SHPT. Female sex, long dialysis duration, and high serum levels of intact parathyroid hormone and alkaline phosphatase may be potential risk factors for SS.

Gene therapy for psoriasis in the K14-VEGF transgenic mouse model by topical transdermal delivery of interleukin-4 using ultradeformable cationic liposome.

BACKGROUND: Topical transdermal gene delivery to the skin shows great potential for painless, non-invasive administration of vaccines and therapeutic agents. Interleukin (IL)-4 strategies have shown a good antipsoriatic effect in clinic trials. To date, no information has been acquired on the effectiveness of gene therapy for psoriasis in the K14-VEGF transgenic mouse model by topical transdermal penetration of murine IL-4 (mIL-4) using ultradeformable cationic liposome (UCL). METHODS: In the present study, we synthesized an UCL and determined a suitable formula for transdermally delivering plasmid DNA to mouse skin. We then tested the antipsoriatic efficacy in the K14-VEGF transgenic mouse model by transdermal delivery of mIL-4 using UCL. RESULTS: We found that plasmid DNA was transdermally delivered to vicinal sites of epidermis and hair follicles using this optimized formula. Plasmid DNA expression was detected in ear skin. Twenty-four hours after topical application, plasmid DNA was not detected in blood serum and liver, which may decrease the risk of insertion of promoter from plasmid to genomic DNA. Mice treated with UCL/mIL-4 displayed a mild psoriasis phenotype. Histological analysis of pathological score using the Baker scoring system revealed an antipsoriatic effect. Immunohistochemical analysis revealed that hyperplastic and inflamed vessels were suppressed. CONCLUSIONS: These observations provide evidence of antipsoriatic efficacy by topical transdermal delivery of mIL-4. Therefore, topical transdermal gene transfer is attractive and offers future potential for application in human patients with other dermatogic diseases.

Luminescent dendritic cyclometalated iridium(III) polypyridine complexes: synthesis, emission behavior, and biological properties.

Luminescent dendritic cyclometalated iridium(III) polypyridine complexes [{Ir(N--C)(2)}(n)(bpy-n)](PF(6))(n) (HN--C = 2-phenylpyridine, Hppy, n = 8 (ppy-8), 4 (ppy-4), 3 (ppy-3); HN--C = 2-phenylquinoline, Hpq, n = 8 (pq-8), 4 (pq-4), 3 (pq-3)) have been designed and synthesized. The properties of these dendrimers have been compared to those of their monomeric counterparts [Ir(N--C)(2)(bpy-1)](PF(6)) (HN--C = Hppy (ppy-1), Hpq (pq-1)). Cyclic voltammetric studies revealed that the iridium(IV/III) oxidation and bpy-based reduction occurred at about +1.24 to +1.29 V and -1.21 to -1.27 V versus SCE, respectively, for all the complexes. The molar absorptivity of the dendritic iridium(III) complexes is approximately proportional to the number of [Ir(N--C)(2)(N--N)] moieties in one complex molecule. However, the emission lifetimes and quantum yields are relatively independent of the number of [Ir(N--C)(2)(N--N)] units, suggesting negligible electronic communications between these units. Upon photoexcitation, the complexes displayed triplet metal-to-ligand charge-transfer ((3)MLCT) (dpi(Ir) --> pi*(bpy-n)) emission. The interaction of these complexes with plasmid DNA has been investigated by agarose gel retardation assays. The results showed that the dendritic iridium(III) complexes, unlike their monomeric counterparts, bound to the plasmid, and the interaction was electrostatic in nature. The lipophilicity of all the complexes has been determined by reversed-phase high-performance liquid chromatography (HPLC). Additionally, the cellular uptake of the complexes by the human cervix epithelioid carcinoma (HeLa) cell line has been examined by inductively coupled plasma mass spectrometry (ICP-MS), laser-scanning confocal microscopy, and flow cytometry. Upon internalization, all the complexes were localized in the perinuclear region, forming very sharp luminescent rings surrounding the nuclei. Interestingly, in addition to these rings, HeLa cells treated with the dendritic iridium(III) complexes showed specific labeled compartments, which have been identified to be the Golgi apparatus. Furthermore, the cytotoxicity of these iridium(III) complexes has been evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay.

[Effects of HBsAg pulsed dendritic vaccination on anti-HBs production in immunosuppressed rats after liver transplantation].

OBJECTIVE: To explore the effects of HBsAg pulsed dendritic vaccination on anti-HBs production in immunosuppressed rats after liver transplantation (LT). METHODS: Brown-Norway liver allografts were transplanted into Lewis recipients. The transplanted Lewis rats were injected with EK506 (2 mg/kg) and randomly divided into two groups: rats in HBsAg-DCs group (n = 15) were intraperitoneally injected with HBsAg pulsed DCs at 14 d and 28 d after LT, and rats in the HBsAg group (n = 15) were injected with HBsAg (200 mul) once a week for 12 weeks. Rats without any immunosuppressive treatment after LT served as controls (n = 5). IL-2 and IFN-gamma mRNA expression in spleen were analyzed by RT-PCR, serum IL-2, IFN-gamma and anti-HBs were detected by ELISA. RESULTS: High dose of FK506 resulted in the immunosuppressed in LT rats, as evident by low production of IL-2 and IFN-gamma, and without liver rejection compared to rats in the control group. HBsAg-DCs induced high titer of anti-HBs antibody, however, titer of anti-HBs were seldom detectable in the HBsAg group at 1, 2 and 3 mouth after vaccination. CONCLUSION: The capacity of HBsAg-DCs to induce anti-HBs in immunosuppressed rats suggested that DC vaccine may prevent HBV recurrence in liver transplanted patients.

Ultrasonic/microwave-assisted extraction, simulated digestion, and fermentation in vitro by human intestinal flora of polysaccharides from Porphyra haitanensis.

In this study, we employed a response surface methodology to optimize the ultrasonic/microwave-assisted extraction (UMAE) conditions of Porphyra haitanensis polysaccharides (PHP), and subjected it to a stimulated in vitro digestion and fermentation model in order to investigate the digestion properties of PHP and the effects on human intestinal flora. The optimum extraction conditions consisted of an extraction time of 29.64 min, extraction temperature of 79.94 °C, and solid-liquid ratio of 1:41.79 g/mL. Under these conditions, the maximum yield of PHP predicted was 20.98%. The ζ-potential and thermal properties analysis verified that PHP was a negatively charged polymer, and possessed good thermal stability. Meanwhile, PHP was not digested in vitro by human saliva, simulated gastric and small intestinal juice. Furthermore, PHP modulated the microbiome structure, mainly increasing the relative abundance of Bacteroides and decreasing in the Escherichia_Shigella group. LEfSe analysis illustrated that Bacteroides, Lachnospiraceae_UCG_006 and Bacteroidales_S24_7_group could serve as potential biomarkers for the PHP supplement. This current study proved that the UMAE method was a highly efficient method to extract PHP to the maximum extent, and also provided insight concerning the stability performance of PHP and its prospects for application as a prebiotics candidate in the functional food industries.

A High Barrier and Sustained Release Oxygen-Absorbing Ionic Polymer for Food Packaging Applications.

Development and utilization of oxygen absorbing materials for food and beverage packaging are important to protect the oxygen-sensitive foods. In this study, we developed a kind of ionic polymer with excellent oxygen absorbing ability based on reacting ethylene-acrylic acid copolymer (EAA) and sodium sulfite (Na2 SO3 ). By virtue of the hydrophilicity of the ionic polymer, the sulfite in Na2 SO3 is easily hydrolyzed and ionized. The oxygen inhalation reaction was gradually initiated and started, whereas achieved a slow and controllable oxygen absorption process. The oxygen absorbing agent can be directly added in the form of an auxiliary agent, which greatly simplifies the preparation process of the oxygen absorbing material. Furthermore, the ionic structure of the EAA/Na2 SO3 composites were destroyed and mechanical properties of the material did not decrease after oxygen absorption. More importantly, it can effectively prevent the entry of external oxygen because the ionic polymer itself has better barrier properties. PRACTICAL APPLICATION: Typical oxygen-sensitive objects include: beer, coffee, canned food, meat products, dairy products, and so on. The presence of oxygen in the package can cause microbial growth, odor generation, color change and nutrient loss, resulting in a significant reduction in food shelf life. Therefore, controlling the oxygen content of the food package is important to limit the rate of these spoilage and spoilage reactions in the food. Materials with active oxygen scavenging and good barrier properties and packaging performance are highly economically viable in terms of improving product quality and reducing packaging costs.

Effects of xipayi mouth rinse combined with minocycline on localized aggressive periodontitis' therapeutic effect and the levels of CRP, TNF-α, IL-6 in serum.

BACKGROUND: Localized aggressive periodontitis is rare periodontitis in clinical practice, which often occurs in young adults under 35 years old, seriously affecting patients' quality of life. As a tetracycline antibacterial drug, minocycline is also considered an essential choice to treat periodontal disease. However, few reports focused on the effect of xipayi mouth rinse combined with minocycline on periodontal pathogens. The goal of this study was to investigate the clinical effect of xipayi mouth rinse combined with minocycline in the treatment of localized aggressive periodontitis and its effect on the levels of CRP, TNF-α, and IL-6. METHODS: Ninety-six patients with limited aggressive periodontitis were selected and randomly divided into two groups. Forty-eight patients in the control group were treated with xipayi mouth rinse after primary periodontal treatment. Then, 48 patients in the experimental group were treated with xipayi mouth rinse combined with minocycline after primary periodontal treatment. The periodontal probe was applied to detect periodontal plaque index (PLI), periodontal pocket depth (PD), sulcus bleeding index (SBI), gingival index (GL), and clinical attachment loss (CAL) before and after treatment in both groups of patients. ELISA was used for detecting the expression levels of CRP, TNF-α, and IL-6 in the serum of patients in two groups before and after treatment. We compared the recurrence rates of the two groups after a 1-year follow-up. RESULTS: Compared with the control group, the PLI, PD, SBI, GL, CAL, and total masticatory efficiency of the experimental group were significantly better than those of the control group. The levels of inflammatory factors CRP, TNF-α, and IL-6 were significantly declined, and the total effective rate of treatment was significantly elevated. After follow-up, it was found there was no noticeable difference in the recurrence rate between the two groups. CONCLUSIONS: Xipayi mouth rinse, combined with minocycline in the treatment of localized aggressive periodontitis, can significantly improve the periodontal gingival condition and reduce the level of inflammatory factors. Also, the efficacy of the treatment was significant. This experiment has provided ideas for improving the clinical treatment of patients with localized aggressive periodontitis.

Flexible and fully implantable upconversion device for wireless optogenetic stimulation of the spinal cord in behaving animals.

Wireless optogenetics based on the upconversion technique has recently provided an effective and interference-free alternative for remote brain stimulation and inhibition in behaving animals, which is of great promise for neuroscience research. However, more versatile upconversion devices are yet to be implemented for neural tissues other than the brain. In this study, a flexible and fully implantable upconversion device was developed for epidural spinal cord stimulation. The upconversion device was fabricated via a straightforward, two-step, heat-pulling process using biocompatible thermoplastic polypropylene as a backbone, which is mixed with upconversion nanoparticles (UCNPs) to form a flexible optrode device that converts near-infrared (NIR) irradiation to visible light for the optogenetic manipulation of spinal cord tissues. In this system, the flexible upconversion device is fully implantable within the rigid spine structure, and shows excellent long-term biocompatibility even after a four-month experiment. In anesthetized mice, the UCNP device implanted at the L4 vertebra can be used to reliably evoke hindlimb muscular activity upon NIR triggering. In behaving mice, neural modulation by the same UCNP devices effectively inhibits the animals' movement as a result of remote spinal cord stimulation. We believe that the flexible upconversion device provides new possibilities for wireless neural modulation in spinal cord tissues, and will become a valuable supplement to the current tool sets of upconversion based wireless optogenetics.

Thermally Triggered, Cell-Specific Enzymatic Glyco-Editing: In Situ Regulation of Lectin Recognition and Immune Response on Target Cells.

In situ glyco-editing on the cell surface can endow cellular glycoforms with new structures and properties; however, the lack of cell specificity and dependence on cells' endogenous functions plague the revelation of cellular glycan recognition properties and hamper the application of glyco-editing in complicated authentic biosystems. Herein, we develop a thermally triggered, cell-specific glyco-editing method for regulation of lectin recognition on target live cells in both single- and cocultured settings. The method relies on the aptamer-mediated anchoring of microgel-encapsulated neuraminidase on target cells and subsequent thermally triggered enzyme release for localized sialic acid (Sia) trimming. This temperature-based enzyme accessibility modulation strategy exempts genetic or metabolic engineering operations and, thus for the first time, enables tumor-specific desialylation on complicated tissue slices. The proposed method also provides an unprecedented opportunity to potentiate the innate immune response of natural killer cells toward target tumor cells through thermally triggered cell-specific desialylation, which paves the way for in vivo glycoimmune-checkpoint-targeted cancer therapeutic intervention.

Liposomal honokiol inhibits VEGF-D-induced lymphangiogenesis and metastasis in xenograft tumor model.

Lymph nodes metastasis of tumor could be a crucial early step in the metastatic process. Induction of tumor lymphangiogenesis by vascular endothelial growth factor-D may play an important role in promoting tumor metastasis to regional lymph nodes and these processes can be inhibited by inactivation of the VEGFR-3 signaling pathway. Honokiol has been reported to possess potent antiangiogenesis and antitumor properties in several cell lines and xenograft tumor models. However, its role in tumor-associated lymphangiogenesis and lymphatic metastasis remains unclear. Here, we established lymph node metastasis models by injecting overexpressing VEGF-D Lewis lung carcinoma cells into C57BL/6 mice to explore the effect of honokiol on tumor-associated lymphangiogenesis and related lymph node metastasis. The underlying mechanisms were systematically investigated in vitro and in vivo. In in vivo study, liposomal honokiol significantly inhibited the tumor-associated lymphangiogenesis and metastasis in Lewis lung carcinoma model. A remarkable delay of tumor growth and prolonged life span were also observed. In in vitro study, honokiol inhibited VEGF-D-induced survival, proliferation and tube-formation of both human umbilical vein endothelial cells (HUVECs) and lymphatic vascular endothelial cells (HLECs). Western blotting analysis showed that liposomal honokiol-inhibited Akt and MAPK phosphorylation in 2 endothelial cells, and downregulated expressions of VEGFR-2 of human vascular endothelial cells and VEGFR-3 of lymphatic endothelial cells. Thus, we identified for the first time that honokiol provided therapeutic benefit not only by direct effects on tumor cells and antiangiogenesis but also by inhibiting lymphangiogenesis and metastasis via the VEGFR-3 pathway. The present findings may be of importance to investigate the molecular mechanisms underlying the spread of cancer via the lymphatics and explore the therapeutical strategy of honokiol on antilymphangiogenesis and antimetastasis.