The relationship between human blood metabolites and preeclampsia-eclampsia: A Mendelian randomization study.

Preeclampsia and eclampsia are serious complications of pregnancy, leading to high rates of maternal and neonatal mortality. During pregnancy, there are changes in relevant serum metabolites in women. However, it remains unclear if these serum metabolites contribute to the development of associated disorders during pregnancy. Therefore, we conducted a Mendelian randomization study to explore the causal relationship between serum metabolites and preeclampsia and eclampsia. We utilized the inverse variance weighted model as our primary analysis approach. We complemented this with sensitivity analyses, including the heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis, to ensure the robustness of our findings. Furthermore, we conducted linkage disequilibrium score regression, multivariable Mendelian randomization, and metabolic pathway analysis to further explore the genetic data. The Mendelian randomization analysis has identified γ-glutamylglutamine, inosine, and isoleucine 10 metabolites that are significantly associated with preeclampsia, and γ-glutamylglutamine and phenylacetate 8 metabolites that may potentially contribute to the development of eclampsia. Notably, γ-glutamylglutamine has been found to have a causal relationship with both preeclampsia and eclampsia. In the multivariable Mendelian randomization analysis, our research findings suggest that both isoleucine and X-14304-leucylalanine directly impact preeclampsia within the context of amino acids and peptides. Moreover, our observations reveal that carbohydrates can also have a direct effect on preeclampsia. Importantly, it should be emphasized that only 3-lactate in amino acids has been shown to have a direct influence on eclampsia. This research has the potential to enhance our understanding of the biological variances related to disease status, providing a foundation for future investigations.

Establishment of a CaCC-based Cell Model and Method for High-throughput Screening of M3 Receptor Drugs.

Muscarinic acetylcholine receptor subtype 3 (M3 receptor) is a G Protein-Coupled Receptor (GPCR) that mediates many important physiological functions. Currently, most M3 receptor drugs also have high affinity for other subtypes of muscarinic acetylcholine receptors (mAChRs) and produce the risk of side effects. Therefore, in order to find M3 receptor drugs with high specificity, high activity and low side effects, we established a cell model and method for efficient and sensitive screening of M3 receptor based on calcium-activated chloride channels (CaCCs), and this method is also suitable for the screening of other GPCR drugs. This screening model consists of Fischer rat thyroid follicular epithelial (FRT) cells that endogenously express M3 receptors, CaCCs, and the indicator YFP-H148Q/I152L. We verified that the model can sensitively detect changes in intracellular Ca2+ concentration using fluorescence quenching kinetics experiments, confirmed the screening function of the model by applying available M3 receptor drugs, and also evaluated the good performance of the model in high-throughput screening.

[Establishment of a CFTR-based detection method for the second messenger cAMP in the cytoplasm].

Objective: To establish a detection method based on Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) that can sensitively detect the second messenger cyclic AMP (cAMP) in the cytoplasm. Methods: The eukaryotic expression vectors of CFTR and YFP-H148Q / I152L were constructed respectively. FRT cells co-expressing CFTR and YFP-H148Q / I152L were obtained by liposome transfection. The expression of CFTR and YFP-H148Q / I152L in FRT cells was observed by an inverted fluorescence microscopy, and flow cytometry was used to detect the purity of cells; The cell model was identified by the fluorescence quenching kinetics test. The validation of the cell model which could screen CFTR modulators was verified by the fluorescence quenching kinetics experiments. The radioimmunoassay was used to detect the cAMP concentration in cytoplasm after adding CFTR activator. Results: The results of the inverted fluorescence microscope showed that CFTR was expressed in the cell membrane and YFP-H148Q / I152L was expressed in the cytoplasm of FRT cells. The FRT cell model stably co-expressing ANO1 and YFP-H148Q / I152L was successfully constructed. The model could screen CFTR modulators, and the slope of fluorescence change and the concentration of CFTR modulators were in a dose-dependent manner. The slope of the fluorescence could reflect the cAMP concentration in the cytoplasm. The cell model could sensitively detect the intracellular cAMP concentration. Conclusion: The cell model could efficiently and sensitively detect the second messenger cAMP concentration in the cytoplasm, and it provided a simple and efficient method for the study of other targets associated cAMP signal.

Establishment of a Cell Model for Dynamic Monitoring of Intracellular Calcium Concentration and High-Throughput Screening of P2Y2 Regulators.

P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular nucleotides. The P2Y2 receptor subtype is expressed in a variety of cell types and plays an important role in physiological and pathophysiological processes such as inflammatory responses and neuropathic pain. Based on this, the P2Y2 has been identified as an important drug target. The specificity of current P2Y2 receptor modulators is relatively poor, and currently, specific and efficient P2Y2 receptor modulators and efficient screening strategies are lacking. In this study, a cell model based on calcium-activated chloride channels (CaCCs) was established that can detect changes in intracellular calcium concentrations and can be used to high-throughput screen for P2Y2 receptor-specific regulators. This screening strategy is suitable for screening of most G-protein-coupled receptor regulators that mediate increases in intracellular calcium signals. The cell model consists of three components that include the endogenously expressed P2Y2 receptor protein, the exogenously expressed calcium-activated chloride channel Anoctamin-1 (Ano1), and a yellow fluorescent protein mutant expressed within the cell that is highly sensitive to iodine ions. This model will allow for high-throughput screening of GPCR regulators that mediate increased intracellular calcium signaling using the calcium-activated transport of iodide ions by Ano1. We verified the ability of the model to detect intracellular calcium ion concentration using fluorescence quenching kinetic experiments by applying existing P2Y2 agonists and inhibitors to validate the screening function of the model, and we also evaluated the performance of the model in the context of high-throughput screening studies. The experimental results revealed that the model could sensitively detect intracellular calcium ion concentration changes and that the model was accurate in regard to detecting P2Y2 modulators. The resultant value of the Z-factor was 0.69, thus indicating that the model possesses good sensitivity and specificity.

Removal of Cd2+ from water containing Ca2+ and Mg2+ using titanate nanotubes modified by carbon.

Calcium and magnesium ions usually exist in natural water. When Cd2+ is removed from water by adsorption, it will be inhibited by these two ions. Titanate nanotubes (TNTs) have an effective adsorption capacity for Cd2+ due to extraordinary ion exchange property. However, TNTs also adsorb Ca2+ and Mg2+ in water. In this study, carbon-modified TNT (TNT/C) and TNT/C further treated with acid (TNT/HC) were synthesized by hydrothermal synthesis. The transmission electron microscope (TEM) images show that TNT/C or TNT/HC still keep nanotube morphology. The experimental results show the order of adsorption amount to Cd2+ is TNT (171.56 mg/g) > TNT/C (166 mg/g) > TNT/HC (159.88 mg/g) when there is no Ca2+ or Mg2+. But when there is 0.1 M Ca2+ or Mg2+ in the water, the order of Cd2+ adsorption capacity becomes TNT/HC (44.28, 49.04 mg/g) > TNT/C (58.84, 69.32 mg/g) > TNT (65.52, 70.6 mg/g). It indicates that the surface carbon modification can alleviate the hindrance of Ca2+ or Mg2+ to Cd2+ removal. This is because the carbon on the surface of TNT captured part of Ca2+ or Mg2+; it made more Cd2+ be successfully absorbed by TNT through ion exchange. This mechanism was confirmed by the X-ray photoelectron spectroscopy (XPS) spectra analysis. The results of this paper can provide ideas for the adsorption and removal of Cd2+ in water in the presence of Ca2+ or Mg2+.

Suite of Organoplatinum(II) Triangular Metallaprism: Aggregation-Induced Emission and Coordination Sequence Induced Emission Tuning.

A series of triangular metallaprisms with a kinetically inert Pt-N bond have been synthesized from the stepwise assembly of a Pt-corner, linear linker 4,4'-bipy (4,4'-bipy = 4,4'-bipyridine) and triangular ligand [tpb or tpt, tpb = tris(4-pyridyl)benzene, tpt = tris(4-pyridyl)triazine]. The use of an unsymmetrical [Pt(HL)]-corner (H2L = 2,6-diphenylpyridine) leads to novel isostructural products. Phenyl rotation at the metal-corners endows these complexes with good aggregation-induced emission (AIE) function, with varied activities across the isostructural complexes. The coordination sequence of electron-deficient ligand tpt also imparts significant influence on the complex emission. These organoplatinum triangular metallaprisms thus provide a good model to study the influence of building blocks and coordination sequence on the luminescence of supramolecules.

Sub-5 nm Ultra-Fine FeP Nanodots as Efficient Co-Catalysts Modified Porous g-C3N4 for Precious-Metal-Free Photocatalytic Hydrogen Evolution under Visible Light.

Sub-5 nm ultra-fine iron phosphide (FeP) nano-dots-modified porous graphitic carbon nitride (g-C3N4) heterojunction nanostructures are successfully prepared through the gas-phase phosphorization of Fe3O4/g-C3N4 nanocomposites. The incorporation of zero-dimensional (0D) ultra-small FeP nanodots co-catalysts not only effectively facilitate charge separation but also serve as reaction active sites for hydrogen (H2) evolution. Herein, the strongly coupled FeP/g-C3N4 hybrid systems are employed as precious-metal-free photocatalysts for H2 production under visible-light irradiation. The optimized FeP/g-C3N4 sample displays a maximum H2 evolution rate of 177.9 µmol h-1 g-1 with the apparent quantum yield of 1.57% at 420 nm. Furthermore, the mechanism of photocatalytic H2 evolution using 0D/2D FeP/g-C3N4 heterojunction interfaces is systematically corroborated by steady-state photoluminescence (PL), time-resolved PL spectroscopy, and photoelectrochemical results. Additionally, an increased donor density in FeP/g-C3N4 is evidenced from the Mott-Schottky analysis in comparison with that of parent g-C3N4, signifying the enhancement of electrical conductivity and charge transport owing to the emerging role of FeP. The density functional theory calculations reveal that the FeP/g-C3N4 hybrids could act as a promising catalyst for the H2 evolution reaction. Overall, this work not only paves a new path in the engineering of monodispersed FeP-decorated g-C3N4 0D/2D robust nanoarchitectures but also elucidates potential insights for the utilization of noble-metal-free FeP nanodots as remarkable co-catalysts for superior photocatalytic H2 evolution.

Morphological Growth and Theoretical Understanding of Gold and Other Noble Metal Nanoplates.

For the last decades, the chemical reduction of Au3+ to Au0 has been widely employed to produce various gold nanostructures. In comparison with the fast reduction, the slow reduction is systematically investigated in this research to provide more insights to reveal intermediary process and further disclose the underlying mechanism for growing gold nanostructures by using a series of simple ligands with aldehyde groups as weak reducing agents. The different binding energies of ligands to Aun+ (n=3, 1 and 0) exhibit variable binding affinities in starting, intermediate, and final gold species. For example, formic acid has much stronger binding affinity to Au+ than Au3+ , and thus Au+ intermediate is able to be stabilized/captured during slow reduction of Au3+ . Upon the disproportionation of Au+ to Au0 and Au3+ , formic acid has much stronger binding affinity to the newly formed Au0 than other ligands for the controlled formation of gold nanostructures. Meanwhile, the adsorption of ligands causes substantially decreased surface energies on different gold planes. There are much higher energies on {110} planes compared to the other two {111} and {100} planes with certain ratios in these energies, leading to morphological growth of gold nanosheets. In this paper, we experimentally demonstrate anisotropic growth of gold nanosheets by using various ligands with weak reducing and appropriate coordination capabilities, and further provide insights to understand their morphological growth mechanism behind. This synthetic strategy is successfully extended to prepare silver, palladium, and platinum nanoplates.

Processing Preference Toward Object-Extracted Relative Clauses in Mandarin Chinese by L1 and L2 Speakers: An Eye-Tracking Study.

The current study employed an eye-movement technique with an attempt to explore the reading patterns for the two types of Chinese relative clauses, subject-extracted relative clauses (SRCs) and object-extracted relative clauses (ORCs), by native speakers (L1), and Japanese learners (L2) of Chinese. The data were analyzed in terms of gaze duration, regression path duration, and regression rate on the two critical regions, head noun, and embedded verb. The results indicated that both the L1 and L2 participants spent less time on the head nouns in ORCs than in SRCs. Also, the L2 participants spent less time on the embedded verbs in ORCs than in SRCs and their regression rate for embedded verbs was generally lower in ORCs than in SRC. The findings showed that the participants experienced less processing difficulty in ORCs than SRCs. These results suggest an ORC preference in L1 and L2 speakers of Chinese, which provides evidence in support of linear distance hypothesis and implies that the syntactic nature of Chinese is at play in the RC processing.

The effect of total hip arthroplasty on sagittal spinal-pelvic-leg alignment and low back pain in patients with severe hip osteoarthritis.

PURPOSE: Sagittal spinopelvic malalignment has been reported in spinal disorders such as low back pain (LBP), and restoration of normal alignment is targeted when treating these disorders. Abnormal sagittal spinal-pelvic-leg alignment has been reported in patients with severe hip osteoarthritis (OA), who have a high prevalence of associated LBP. This prospective longitudinal study aimed to investigate changes in sagittal spinal-pelvic-leg alignment after total hip arthroplasty (THA) in patients with severe hip OA, and whether these changes contribute to LBP relief. METHODS: Patients undergoing primary THA due to severe unilateral hip OA were recruited. Physical examination and X-ray films were taken to rule out any spinal disorder. Sagittal alignment of pelvis, hip, and spine was analyzed on lateral radiographs taken before (baseline) and 1 year after (follow-up) THA. Functional instruments were completed by patients including: visual analog scale (VAS) for LBP, Roland-Morris Disability Questionnaire (RMDQ), and Harris Hip Score (HHS). Comparisons were carried out at baseline and follow-up, and between patients with and without LBP. RESULTS: The recruited 69 patients showed significantly reduced hip flexion and improved global spinal balance at follow-up compared with baseline. LBP was reported by 39 patients (56.5 %) before surgery; at follow-up, 17 reported complete resolution, while 22 reported significant relief. Significant decreases in VAS and RMDQ scores in lumbar spine and increase in hip HHS were observed. CONCLUSIONS: THA in patients with severe hip OA could help correct abnormal sagittal spinal-pelvic-leg alignment and relieve comorbid LBP. Improvements in hip flexion and global spinal balance might be involved in the mechanism of LBP relief.

Investigating the Processing of Relative Clauses in Mandarin Chinese: Evidence from Eye-Movement Data.

A number of previous studies on Chinese relative clauses (RC) have reported conflicting results on processing asymmetry. This study aims to revisit the prevalent debate on whether subject-extracted RCs (SRC) or object-extracted RCs (ORC) are easier to process by using the eye-movement technique. In the current study, the data are analyzed in terms of the gaze duration and regression of eye-movement in three critical areas: head noun, embedded verb, and RC-modifying noun phrase as subject. The results show an ORC preference for the processing of RC structures, which supports the word-order account and the Dependency Locality Theory, and a better cross-clausal integration for SRC, which supports the perspective-shift account. The processing asymmetry in Chinese RCs are discussed under relevant theoretical accounts, such as structure-based, memory-based, and perspective shift accounts. We argue that the findings are associated with the syntactic nature of Chinese (a head-initial language with pre-nominal RCs).

Layer-by-layer-assembled healable antifouling films.

Healable antifouling films are fabricated by the exponential layer-by-layer assembly of PEGylated branched poly(ethylenimine) and hyaluronic acid followed by post-crosslinking. The antifouling function originates from the grafted PEG and the extremely soft nature of the films. The rapid and multiple healing of damaged antifouling functions caused by cuts and scratches can be readily achieved by immersing the films in normal saline solution.

Rapid Copper Metallization of Textile Materials: a Controlled Two-Step Route to Achieve User-Defined Patterns under Ambient Conditions.

Throughout history earth-abundant copper has been incorporated into textiles and it still caters to various needs in modern society. In this paper, we present a two-step copper metallization strategy to realize sequentially nondiffusive copper(II) patterning and rapid copper deposition on various textile materials, including cotton, polyester, nylon, and their mixtures. A new, cost-effective formulation is designed to minimize the copper pattern migration on textiles and to achieve user-defined copper patterns. The metallized copper is found to be very adhesive and stable against washing and oxidation. Furthermore, the copper-metallized textile exhibits excellent electrical conductivity that is ~3 times better than that of stainless steel and also inhibits the growth of bacteria effectively. This new copper metallization approach holds great promise as a commercially viable method to metallize an insulating textile, opening up research avenues for wearable electronics and functional garments.

Examining the online reading behavior and performance of fifth-graders: evidence from eye-movement data.

Online reading is developing at an increasingly rapid rate, but the debate concerning whether learning is more effective when using hypertexts than when using traditional linear texts is still persistent. In addition, several researchers stated that online reading comprehension always starts with a question, but little empirical evidence has been gathered to investigate this claim. This study used eye-tracking technology and retrospective think aloud technique to examine online reading behaviors of fifth-graders (N = 50). The participants were asked to read four texts on the website. The present study employed a three-way mixed design: 2 (reading ability: high vs. low) × 2 (reading goals: with vs. without) × 2 (text types: hypertext vs. linear text). The dependent variables were eye-movement indices and the frequencies of using online reading strategy. The results show that fifth-graders, irrespective of their reading ability, found it difficult to navigate the non-linear structure of hypertexts when searching for and integrating information. When they read with goals, they adjusted their reading speed and the focus of their attention. Their offline reading ability also influenced their online reading performance. These results suggest that online reading skills and strategies have to be taught in order to enhance the online reading abilities of elementary-school students.

Characteristics of sagittal spine-pelvis-leg alignment in patients with severe hip osteoarthritis.

PURPOSE: The interaction between the sagittal alignment of the spine and pelvis and the compensatory mechanism in patients suffering from spinal disorders has been well documented. However, in patients with hip osteoarthritis (HOA), few studies have explored how the hip joint pathology could affect the sagittal alignment of the hip, pelvis and spine, and no reports have investigated whether these changes are involved in the pathogenesis of low back pain in these patients. The aims of this case-control study were to investigate the sagittal spine-pelvis-leg alignment in patients suffering from severe HOA and to understand whether the alignment was related to the occurrence of low back pain and the health-related quality of life in these patients. METHODS: Fifty-eight patients with severe HOA and 64 asymptomatic controls were studied. Digital lateral X-rays of the spine, pelvis and proximal femur were obtained with the patients placed in upright positions. The following radiographic parameters were measured to examine the sagittal alignment of the pelvis, hip and spine: pelvic incidence (PI), pelvic tilting (PT), sacral slope (SS), pelvic femoral angle (PFA), femoral inclination (FI), lumbar lordosis (LL), spino-sacral angle (SSA), C7 tilt (C7T) and T1 spinal-pelvic inclination (T1-SPI). The global balance patterns of spinal-pelvic alignment were classified as normal balance, slight unbalance and severe unbalance according to the relative position of the C7 plumb line to the sacrum and femoral heads. Short Form-36 questionnaire was carried out in the patients. Comparisons were carried out between the patients with HOA and the controls and between the HOA patients with or without low back pain. Correlation analysis was used to measure relationships between the HOA patients' parameters. RESULTS: There were no significant differences in the age and gender distribution between the HOA patients and control. Compared with the controls, the patients with HOA showed significantly higher SS and lower PT, similar PI in the pelvis, significantly smaller C7T, larger T1-SPI but comparable LL and SSA in the spine, and significantly smaller PFA but larger FI in the hip joint. In addition, the patients with HOA had a significantly greater incidence of severe unbalanced spinal-pelvic alignment than did the controls (22.4 vs 3.1 %, respectively). In patients with HOA, the PFA was significantly correlated with SS, SSA and FI but not with PI, LL or C7T; while the physical component score of short form-36 was significantly correlated with T1-SPI, C7T and FI. A comparison between the HOA patients with or without low back pain, however, showed no significant differences in the radiographic parameters, global sagittal balance patterns and Short Form-36. CONCLUSIONS: The sagittal morphology of the pelvis in patients with severe HOA was normal and might not be involved in the development and progression of this disorder. Although the whole spine was involved in compensating for the flexed hip joint, the poor ability resulted in severely unbalanced spinal-pelvic alignment in these patients. The forward inclined spine and retroverted femur would contribute to the poor physical activities in these patients. However, the abnormal sagittal spine-pelvis-leg alignment in patients with severe HOA might not be involved in the pathogenesis of low back pain.

Robust, flexible, and bioadhesive free-standing films for the co-delivery of antibiotics and growth factors.

Free-standing polymer films that adhere strongly to tissue and can codeliver multiple therapeutic agents in a controlled manner are useful as medical plasters. In this study, a bilayer polymer film comprising a drug reservoir layer and a supporting layer is fabricated by spin-coating poly(lactic-co-glycolic acid) (PLGA) on top of a layer-by-layer assembled film of poly(ß-amino esters) (PAE), alginate sodium (ALG), and recombinant human basic fibroblast growth factor (bFGF). Apart from bFGF, the bilayer film can also load antibiotic drug ceftriaxone sodium (CTX) by a postdiffusion process. The PLGA supporting layer facilitates the direct peeling of the bilayer film from substrate to produce a robust and flexible free-standing film with excellent adhesion onto the human skin and porcine liver. The excellent adhesion of the bilayer film originates from the ALG component in the drug reservoir layer. CTX is quickly released by easily breaking its electrostatic interaction with the drug reservoir layer, whereas the sustained release of bFGF is due to the slow degradation of PAE component in the drug reservoir layer. Wounds can be synergetically treated by fast release of CTX to effectively eradicate invasive bacteria and by sustained release of bFGF to accelerate wound healing. Our results serve as a basis for designing multifunctional free-standing films with combination therapy for biomedical applications.

Sacrum pubic incidence and sacrum pubic posterior angle: two morphologic radiological parameters in assessing pelvic sagittal alignment in human adults.

PURPOSE: The morphology and position of pelvis are critical in regulating the biomechanical organization of spine-pelvis-leg in the sagittal plane. Several radiological parameters have been developed to present the sagittal morphology of the pelvis such as pelvic incidence (PI) and Jackson's angle (PRS1). In addition, the femoral sacral posterior angle (FSPA) was developed for patients with a dome-shaped deformity in the upper plate of the sacrum. The identification of hip axis, which was represented by the line connecting the centers of femoral heads in normal subjects, was important for these parameters measurement. However, in subjects with fused hip joint or deformed femoral heads, the accurate localization of hip axis become imprecise. Herein, the upper edge of the pubic symphysis, which is easy to identify on the lateral X-ray film, was selected as an alternative landmark of the hip axis, and two morphologic parameters, the sacrum pubic incidence (SPI) and sacrum pubic posterior angle (SPPA), were proposed accordingly. The present study aimed to understand the reliability of these two parameters and their value in predicting PI, PRS1 and FSPA. METHODS: Upright standing spine and pelvis radiographs of 60 normal adults (30 male and 30 female) with an average age of 38.5 years were obtained. Two independent observers then measured the following radiological parameters on the films: PI, PRS1, FSPA, SPI, SPPA, sacral slope, pelvic tilt and lumbar lordosis. The SPI is the angle between the line perpendicular to the superior plate of the first sacral vertebra at its midpoint and the line connecting this point to the upper edge of the pubic symphysis, while the SPPA is the angle between the line extending from the posterior upper edge of the sacrum to the upper edge of the pubic symphysis and the posterior side of the first sacral vertebral body. The intra-observer and inter-observer reliabilities of the parameters were analyzed using intraclass correlations. The correlations between parameters were analyzed by Pearson's correlation coefficients. Regression analysis was carried out to establish formulas to predict the values of PI, PRS1 and FSPA using the SPI and SPPA. A p < 0.05 was considered statistically significant. RESULTS: The SPI was 64.4° ± 9.5° and 68.3° ± 9.4°, and the SPPA was 77.7° ± 7.5° and 78.7° ± 9.4° in males and females, respectively. These radiological parameters showed excellent intra- and inter-observer reliabilities, with an intraclass correlation >0.8. No gender differences were identified in these morphologic and positional radiological parameters. The SPI demonstrated strong correlation with PI and PRS1 (R (2) > 0.9, p < 0.001). In addition, strong correlation was also found between SPPA and FSPA (R (2) > 0.9, p < 0.001). Furthermore, both SPPA and FSPA showed close correlations with the other morphologic and positional parameters. Linear regression analysis established equations to predict PI and PRS1 using SPI and to predict FSPA by SPPA with significantly high reliability. CONCLUSIONS: Both SPI and SPPA are reliable parameters for determining the morphology of the pelvis. The SPI is precise in predicting PI and PRS1, while SPPA is reliable in predicting FSPA. The SPI and SPPA will allow further study on lateral spinal-pelvic alignment in patients with hip joint abnormalities.

Robust and flexible free-standing films for unidirectional drug delivery.

Robust and flexible free-standing polymer films for unidirectional drug delivery are fabricated by sandwiching drug-containing polyelectrolyte multilayer films between poly(lactic-co-glycolic acid) (PLGA) barrier and capping layers. The drug-containing films are fabricated by layer-by-layer (LbL) assembly of chemically cross-linked poly(allylamine hydrochloride)-dextran (PAH-D) microgel and hyaluronic acid (HA), which can load negatively charged cancer-inhibiting drug, methotrexate (MTX). Because the PLGA barrier layer effectively blocks MTX release, MTX can be predominantly released from the PLGA capping layer of the free-standing film. This increases the efficacy of released MTX to cancer cells while minimizing its side effects on the normal tissues. We believe that the unidirectional drug delivery free-standing films can open a new avenue to design of highly efficient drug delivery systems for biomedical application.