Stable and permeable polyion complex vesicles designed as enzymatic nanoreactors.

Polymeric vesicles are perspective vehicles for fabricating enzymatic nanoreactors towards diverse biomedical and catalytic applications, yet the design of stable and permeable vesicles remains challenging. Herein, we developed polyion complex (PIC) vesicles featuring high stability and a permeable membrane for adequate enzyme loading and activation. Our design relies on co-assembly of an anionic diblock copolymer (PSS96-b-PEO113) with cationic branched poly(ethylenimine) (PEI). The polymer combination endows strong electrostatic interaction between the PSS and PEI building blocks, so their assembly can be implemented at a high salt concentration (500 mM NaCl), under which the charge interaction of the enzyme-polymer is inhibited. This control realizes the successful and safe loading of enzymes associated with the formation of stable PIC vesicles with an intrinsic permeable membrane that is favourable for enhancing enzymatic activity. The control factors for vesicle formation and enzyme loading were investigated, and the general application of loading different enzymes for cascade reaction was validated as well. Our study reveals that proper design and combination of polyelectrolytes is a facile strategy for fabricating stable and permeable polymeric PIC vesicles, which exhibit clear advantages for loading and activating enzymes, consequently boosting their diverse applications as enzymatic nanoreactors.

Sulfur-Containing Persistent Free Radicals and Reactive Species on Photoaged Microplastics: Identification and the Formation Mechanism.

The elemental composition may affect the persistent free radical (PFR) and reactive species (RS) formation associated with photoaging microplastics; however, a relevant study is still lacking. This study systematically investigated the formation, evolution, and types of PFRs and RS on sulfur-containing microplastics (S-MPs) under simulated sunlight. Electron paramagnetic resonance detection and power saturation curve analysis isolated three different PFRs on each photoaging poly(phenylene sulfide) (PPS) and polysulfone (PSF). Combining the results of characterization and density functional theory calculation, these observed PFRs on the irradiated S-MPs were classified as oxygen-centered radicals with an adjacent S atom (namely, thio-oxygen radicals), oxygen-centered and sulfur-centered radicals, where the thio-oxygen radicals on PPS were benzenethiol-like radicals, and oxygen-centered radicals and sulfur-centered radicals on PSF that were identified as benzenesulfonic-like radicals and phenyl sulfonyl-like radicals, respectively. Moreover, potential precursor molecule fragments of PFRs on the photoaging S-MPs, including p-toluenesulfinic acid and benzenesulfonic acid, were detected by pyrolysis-gas chromatography/mass spectrometry and liquid chromatography-mass spectrometry. Interestingly, reactive sulfur species (SO3•-) was also observed on irradiated S-MPs in addition to reactive oxygen species, which was mainly derived from the reaction of •OH and sulfonyl radicals. These results have implications for assessing the potential risks of atmospheric S-MPs.

Key Factors of Mechanical Strength and Toughness in Oriented Poly(l-lactic acid) Monofilaments for a Bioresorbable Self-Expanding Stent.

The investigation of the strength and toughness of poly(l-lactic acid) (PLLA) monofilaments is essential as the fundamental element of a biodegradable braided stent. However, the determining factor remains poorly addressed with respect to influencing the mechanical behavior of PLLA monofilaments. In this work, the electron beam (EB) with different radiation doses was utilized to sterilize PLLA monofilaments. Properties of the monofilaments, including the breaking strength, elongation at break, molecular weight, orientation, and microstructure of the fracture, were characterized. Results showed that a random chain scission of PLLA resulting from EB during this process could cause the decrease in molecular weight, which led to the decline in breaking strength. Meanwhile, the irradiated monofilaments were found to have almost the same elongation at break below a dose of 30 kGy and declined by 71.41% up to a dose of 48 kGy. It was also found that the ductile fracture connection of the monofilament translated to the brittle fracture by comparing the microstructure without and with sterilization. These phenomena could originate from the destruction of the long molecular chains connecting the crystal plates into shorter ones by radiation. PLLA monofilaments with 0, 30, and 48 kGy were used to braid carotid stents. Compared with a carotid Wallstent, the PLLA stent can better provide radial supporting to the carotid lesion. This study provides preliminary experimental references to evaluate and predict the mechanical performance of PLLA braided stents.

Decoding Macrophage Subtypes to Engineer Modulating Hydrogels for the Alleviation of Intervertebral Disk Degeneration.

A major pathological basis for low back pain is intervertebral disk degeneration, which is primarily caused by the degeneration of nucleus pulposus cells due to imbalances in extracellular matrix (ECM) anabolism and catabolism. The phenotype of macrophages in the local immune microenvironment greatly influences the balance of ECM metabolism. Therefore, the control over the macrophage phenotype of the ECM is promising to repair intervertebral disk degeneration. Herein, the preparation of an injectable nanocomposite hydrogel is reported by embedding epigallocatechin-3-gallate-coated hydroxyapatite nanorods in O-carboxymethyl chitosan cross-linked with aldehyde hyaluronic acid that is capable of modulating the phenotype of macrophages. The bioactive components play a primary role in repairing the nucleus pulposus, where the hydroxyapatite nanorods can promote anabolism in the ECM through the nucleopulpogenic differentiation of mesenchymal stem cells. In addition, epigallocatechin-3-gallate can decrease catabolism in the ECM in nucleus pulposus by inducing M2 macrophage polarization, which exists in normal intervertebral disks and can alleviate degeneration. The nanocomposite hydrogel system shows promise for the minimally invasive and effective treatment of intervertebral disk degeneration by controlling anabolism and catabolism in the ECM and inhibiting the IL17 signaling pathway (M1-related pathway) in vitro and in vivo.

Focus on the crucial deformation region to adjust the comprehensive performance of poly (L-lactic acid) stent.

The fully biodegradable polymer stent is considered as the fourth-generation vascular implant with good biocompatibility and long-term therapeutic potential. It has attracted much attention because it overcomes the disadvantage of the permanently implanted metal stent. However, compared with the metal stent, its mechanical properties are slightly inferior, which is an urgent problem. Based on previous studies, fully biodegradable polymer stents are prone to experience cracks and damage in large deformation region during the crimping and expansion process. The large deformation region is mainly located at the ring bend of the stent. We supposed that these damages are the leading causes of weakening the mechanical performance of polymer stents and are mainly affected by the crucial deformation region. For this purpose, this work studies the relationship between different crucial deformation regions and the mechanical performance of the polymer stent. Firstly, the volume of the crucial deformation region is improved by increasing the ring width. Although the radial strength of the stent is enhanced with the increase in ring width, the radial stiffness also increases, and correspondingly, the flexibility of the stent decreases. To obtain acceptable comprehensive mechanical performance, two types of slotting design in critical deformation region were proposed. The proposed slotted stent with a bulge has sufficient radial strength and low radial stiffness, having a good radial support capacity and flexibility. In other words, the proposed stent has improved the radial support without sacrificing flexibility. Overall, different crucial deformation regions cause different degrees of damage to the stent during crimping and expansion, which affects the mechanical properties of the stent. Reasonable structural design of the crucial deformation region is the key to adjust the comprehensive performance of the stent.

Protein separation by sequential selective complex coacervation.

In food manufacturing and particular biomedical products selected proteins are often required. Obtaining the desired proteins in a pure form from natural resources is therefore important, but often very challenging. Herein, we design a sequential coacervation process that allows to efficiently isolate and purify proteins with different isoelectric points (pIs) from a mixed solution, namely Bovine Serum Albumin (BSA, pI = 4.9) and Peroxidase from Horseradish (HRP, pI = 7.2). The key to separation is introducing a suitable polyelectrolyte that causes selective complex coacervation at appropriate pH and ionic strength. Specifically, polyethyleneimine (PEI), when added into the mixture at pH 6.0, produces a coacervation which exclusively contains BSA, leading to a supernatant solution containing 100 % HRP with a purity of 91 %. After separating the dilute and dense phases, BSA is recovered by adding poly(acrylic acid) (PAA) to the concentrated phase, which displaces BSA from the complex because it interacts more strongly with PEI. The supernatant phase after this step contains approximately 75 % of the initial amount of BSA with a purity of 99 %. Our results confirm that coacervation under well-defined conditions can be selective, enabling separation of proteins with adequate purity. Therefore, the established approach demonstrates a facile and sustainable strategy with potential for protein separation at industrial scale.

Regulating mechanical performance of poly (l-lactide acid) stent by the combined effects of heat and aqueous media.

Annealing process has been applied to the development of thermoforming polymer braided stent and treating its basic constitute monofilaments, especially for Poly (l-lactide acid) (PLLA) condensed by lactic acid monomer made from the plant starch. In this work, high performance monofilaments were produced by melting spun and solid-state drawing methods. Inspired by the effects of water plasticization on semi-crystal polymer, PLLA monofilaments were annealed with and without constraint in vacuum and aqueous media. Then, the co-effects of water infestation and heat on the micro-structure and mechanical properties of these filaments were characterized. Furtherly, mechanical performance of PLLA braided stents shaped by different annealing methods was also compared. Results showed that annealing in aqueous media generated more obvious structure change of PLLA filaments. Interestingly, the combined effects of aqueous phase and thermal effectively increased the crystallinity, and decreased the molecular weight and orientation of PLLA filaments. Therefore, higher modulus, smaller strength, and elongation at the break for filaments could be obtained, which could furtherly realize better radial compression resistance of the braided stent. This annealing strategy could provide new perspectives between anneal and material properties of PLLA monofilaments, and provide more suitable manufacturing technics for polymer braided stent.

The protective layer formed by soil particles on plastics decreases the toxicity of polystyrene microplastics to earthworms (Eisenia fetida).

The recent discovery of microplastics contaminants in most ecosystems has raised major health issues, yet knowledge on their impact on soil organisms is limited, especially their toxicity evolution with aging. Herein, the toxicity of polystyrene microplastic (PS-MP) to earthworm (Eisenia fetida) along with aging was investigated. Results showed that the 28 d-LC50 (50% lethal concentration) of PS-MP was 25.67 g kg-1, whereas that increased to 96.47 g kg-1 after PS-MP initially aged in soil for 28 days, indicating the toxicity of PS-MP decreased with aging. Laser scanning confocal microscope and scanning electron microscope (SEM) found that the toxicity of PS-MP to earthworm may be due to the ingestion of PS-MP by earthworms and the physical damage (e.g., epidermis abrasion and setae loss) of PS-MP to earthworms. Similarly, the levels of reactive oxygen species, antioxidant enzyme activities and malondialdehyde content increased with PS-MP concentrations from 0.1 to 1.5 g kg-1, but decreased with aging from 7 to 28 days. The integrated biomarker response index also confirmed that the toxicity of PS-MP decreased with aging. SEM found that PS-MP were progressively covered by soil particles during soil aging, inducing the formation of protective layer and increasing the particle size of PS-MP, which prevented direct contact with earthworms and decreased the ingestion of PS-MP, in turn decreased PS-MP toxicity. Overall, our study provides valuable insights for elucidating the effect of aging on the toxicity of microplastics.

Novel PIK3R1 mutation of SHORT syndrome: A case report with a 6-month follow up.

SHORT syndrome (short stature, hyperextensibility, ocular depression [deeply set eyes], Rieger anomaly and teething delay) is very rare, with a few cases reported in the literature. We report a case of SHORT syndrome with a novel PIK3R1 mutation (c.2008delT) and complicated with severe insulin resistance. Although no treatment guidelines are available to relieve insulin resistance in SHORT syndrome, our treatment plans, including lifestyle intervention combined with metformin and pioglitazone, were carried out for this patient. After the intervention, insulin resistance and hyperinsulinemia in this patient were significantly decreased during a 6-month follow up, which showed the effect of our therapeutic strategies.

Identification of Candidate Genes Associated with Charcot-Marie-Tooth Disease by Network and Pathway Analysis.

Charcot-Marie-Tooth Disease (CMT) is the most common clinical genetic disease of the peripheral nervous system. Although many studies have focused on elucidating the pathogenesis of CMT, few focuses on achieving a systematic analysis of biology to decode the underlying pathological molecular mechanisms and the mechanism of its disease remains to be elucidated. So our study may provide further useful insights into the molecular mechanisms of CMT based on a systematic bioinformatics analysis. In the current study, by reviewing the literatures deposited in PUBMED, we identified 100 genes genetically related to CMT. Then, the functional features of the CMT-related genes were examined by R software and KOBAS, and the selected biological process crosstalk was visualized with the software Cytoscape. Moreover, CMT specific molecular network analysis was conducted by the Molecular Complex Detection (MCODE) Algorithm. The biological function enrichment analysis suggested that myelin sheath, axon, peripheral nervous system, mitochondrial function, various metabolic processes, and autophagy played important roles in CMT development. Aminoacyl-tRNA biosynthesis, metabolic pathways, and vasopressin-regulated water reabsorption were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway network, suggesting that these pathways may play key roles in CMT occurrence and development. According to the crosstalk, the biological processes could be roughly divided into a correlative module and two separate modules. MCODE clusters showed that in top 3 clusters, 13 of CMT-related genes were included in the network and 30 candidate genes were discovered which might be potentially related to CMT. The study may help to update the new understanding of the pathogenesis of CMT and expand the potential genes of CMT for further exploration.

Drug-coated balloons used in peripheral artery disease: experience from a single center.

OBJECTIVE: This retrospective single-center study aimed to analyze immediate and follow-up results of using drug-coated balloons (DCBs) for treating peripheral arterial disease. METHODS: In this study, we identified a total of 75 patients who underwent DCB therapy at our institution. The ankle-brachial index (ABI) was measured before and after intervention. Intermittent claudication and whether there was healing of ulcers were determined by telephone. RESULTS: The cohort consisted of 56 men and 19 women aged 38 to 87 years (68 ± 12 years). Twenty-three patients had Rutherford grade III, 15 had Rutherford grade IV, and 37 had Rutherford grade V. Seventeen patients had stents and 18 had the Rotarex system used. The postoperative ABI was significantly greater than the preoperative ABI (0.911 ± 0.173 vs 0.686 ± 0.249). Good results for treatment were obtained. Intermittent claudication and rest pain did not occur in subjects with Rutherford grades III and IV during follow-up. The amputation rate was 4.1% among all patients using DCB therapy during follow-up. CONCLUSIONS: DCB therapy is safe and effective for treating peripheral arterial disease in real-world patients. Future prospective studies on this issue are recommended.

Preliminary results for the treatment of a pain-causing osteoporotic vertebral compression fracture with a Sky Bone Expander.

OBJECTIVE: Vertebral compression fractures (VCFs) are common complications of osteoporosis. The expansion of VCFs with a Sky Bone Expander is a new procedure which improves kyphotic deformities and decreases pain associated with VCFs. The purpose of this study was to investigate the preliminary results for the treatment of painful osteoporotic VCFs with a Sky Bone Expander. MATERIALS AND METHODS: Twenty-six patients with pain-causing VCFs were treated with a Sky Bone Expander. This operation involved the percutaneous insertion of the Sky Bone Expander into a fractured vertebral body transpedicularly. Following the expansion, the Sky Bone Expander was contracted and removed, resulting in a cavity to be filled with bone cement. All fractures were analyzed for improvement in sagittal alignment. Clinical complications, pain relief and ambulation status were evaluated 1 day, 1 week, 1 month, and 3 months after the operation. RESULTS: Twenty-four hours after the operation, all the patients treated experienced some degree of pain relief. In addition, no postoperative neurologic complications were noted. The average operative time was 42.4 +/- 15.5 min per vertebra. Moreover, an average cement volume of 3.5 mL (range, 2.5 +/- 5.0 mL) was injected per vertebra. The average anterior height was 18.4 +/- 5.1 mm preoperatively and 20.5 +/- 5.3 mm postoperatively (p < 0.01). Furthermore, the average midline height was 15.5 +/- 5.2 mm preoperatively and 18.9 +/- 4.0 mm postoperatively (p < 0.01). The Cobb angle improved from 18.5 +/- 8.2 degrees preoperatively to 9.2 +/- 4.0 degrees postoperatively (p < 0.01). The Visual Anabog Scale scores decreased from 7.7 +/- 1.8 points preoperatively to 3.1 +/- 2.0, 2.9 +/- 1.7, 2.6 +/- 1.5 and 2.9 +/- 11.3 after 1 day, 1 week, 1 month and 3 months after the operation, respectively. Cement extrusion was observed in four patients without any neurologic symptoms. CONCLUSION: As a result of this study, we can postulate that the expansion of compressed vetrebra with a Sky Bone Expander is a safe and minimally invasive procedure resulting in the restoration of vertebral body height and the relief of pain associated with VCFs.