Establishment and validation of a nomogram for predicting new fractures after PKP treatment of for osteoporotic vertebral compression fractures in the elderly individuals.

BACKGROUND: To investigate the risk factors for new vertebral compression fractures (NVCFs) after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs) and to create a nomogram to predict the occurrence of new postoperative fractures. METHODS: This was a retrospective analysis of the clinical data of 529 OVCF patients who received PKP treatment in our hospital from June 2017 to June 2020. Based on whether there were new fractures within 2 years after surgery, the patients were divided into a new fracture group and a nonnew fracture group. Univariate and multivariate analyses were used to determine the risk factors for the occurrence of NVCFs after surgery. The data were randomly divided into a training set (75%) and a testing set (25%). Nomograms predicting the risk of NVCF occurrence were created based on the results of the multivariate analysis, and performance was evaluated using receiver operating characteristic curves (ROCs), calibration curves, and decision curve analyses (DCAs). A web calculator was created to give clinicians a more convenient interactive experience. RESULTS: A total of 56 patients (10.6%) had NVCFs after surgery. The univariate analysis showed significant differences in sex and the incidences of cerebrovascular disease, a positive fracture history, and bone cement intervertebral leakage between the two groups (P < 0.05). The multivariate analysis showed that sex [OR = 2.621, 95% CI (1.030-6.673), P = 0.043], cerebrovascular disease [OR = 28.522, 95% CI (8.749-92.989), P = 0.000], fracture history [OR = 12.298, 95% CI (6.250-24.199), P = 0.000], and bone cement intervertebral leakage [OR = 2.501, 95% CI (1.029-6.082), P = 0.043] were independent risk factors that were positively associated with the occurrence of NVCFs. The AUCs of the model were 0.795 (95% CI: 0.716-0.874) and 0.861 (95% CI: 0.749-0.974) in the training and testing sets, respectively, and the calibration curves showed high agreement between the predicted and actual states. The areas under the decision curve were 0.021 and 0.036, respectively. CONCLUSION: Female sex, cerebrovascular disease, fracture history and bone cement intervertebral leakage are risk factors for NVCF after PKP. Based on this, a highly accurate nomogram was developed, and a webpage calculator ( https://new-fracture.shinyapps.io/DynNomapp/ ) was created.

Chromosome engineering of the TCA cycle in Halomonas bluephagenesis for production of copolymers of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV).

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a promising biopolyester with good mechanical properties and biodegradability. Large-scale production of PHBV is still hindered by the high production cost. CRISPR/Cas9 method was used to engineer the TCA cycle in Halomonas bluephagenesis on its chromosome for production of PHBV from glucose as a sole carbon source. Two TCA cycle related genes sdhE and icl encoding succinate dehydrogenase assembly factor 2 and isocitrate lysase were deleted, respectively, in H. bluephagenesis TD08AB containing PHBV synthesis genes on the chromosome, to channel more flux to increase the 3-hydroxyvalerate (3HV) ratio of PHBV. Due to a poor growth behavior of the mutant strains, H. bluephagenesis TY194 equipped with a medium strength Pporin-194 promoter was selected for further studies. The sdhE and/or icl mutant strains of H. bluephagenesis TY194 were constructed to show enhanced cell growth, PHBV synthesis and 3HV molar ratio. Gluconate was used to activate ED pathway and thus TCA cycle to increase 3HV content. H. bluephagenesis TY194 (ΔsdhEΔicl) was found to synthesize 17mol% 3HV in PHBV. Supported by the synergetic function of phosphoenolpyruvate carboxylase and Vitreoscilla hemoglobin encoded by genes ppc and vgb inserted into the chromosome of H. bluephagenesis TY194 (ΔsdhE) serving to enhance TCA cycle activity, a series of strains were generated that could produce PHBV containing 3-18mol% 3HV using glucose as a sole carbon source. Shake flask studies showed that H. bluephagenesis TY194 (ΔsdhE, G7::Pporin-ppc) produced 6.3 g/L cell dry weight (CDW), 65% PHBV in CDW and 25mol% 3HV in PHBV when grown in glucose and gluconate. 25mol% 3HV was the highest reported via chromosomal expression system. PHBV copolymers with different 3HV molar ratios were extracted and characterized. Next-generation industrial biotechnology (NGIB) based on recombinant H. bluephagenesis grown under unsterile and continuous conditions, allows production of P(3HB-0∼25mol% 3HV) in a convenient way with reduced production complexity and cost.

Synthesis and Characterization of Polyhydroxyalkanoate Organo/Hydrogels.

Synthetic organogels/hydrogels are attracting growing interests due to their potential applications in biomedical fields, organic electronics, and photovoltaics. Photogelation methods for synthesis of organogels/hydrogels have been shown particularly promising because of the high efficiency and simple synthetic procedures. This study synthesized new biodegradable polyhydroxyalkanoates (PHA)-based organogels/hydrogels via UV photo-cross-linking using unsaturated PHA copolymer poly[(R)-3-hydroxyundecanoate-co-(R)-3-hydroxy-10-undecenoate] (PHU10U) with polyethylene glycol dithiol (PDT) as a photo-cross-linker. The PHU10U was synthesized by an engineered Pseudomonas entomophila and characterized via Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance (NMR), and 13C NMR. With decreasing the molar ratio of PHU10U to PDT, both the swelling ratio and pore size were decreased. Meanwhile, increasing densities of the gel networks resulted in a higher compressive modulus. Cell cytotoxicity studies based on the CCK-8 assay on both the PHU10U precursor and PHU10U/PDT hydrogels showed that the novel PHA-based biodegradables acting as hydrogels possess good biocompatibility.

Synthesis, Characterization and Application of Thermoresponsive Polyhydroxyalkanoate-graft-Poly(N-isopropylacrylamide).

A thermoresponsive graft copolymer polyhydroxyalkanoate-g-poly(N-isopropylacrylamide) or short as PHA-g-PNIPAm, was successfully synthesized via a three-step reaction. First, PNIPAm oligomer with a trithiocarbonate-based chain transfer agent (CTA), short as PNIPAm-CTA, with designed polymerization degree was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Subsequently, the PNIPAm-CTA was treated with n-butylamine for aminolysis in order to obtain a pendant thiol group at the end of the chain (PNIPAm-SH). Finally, the PNIPAm-SH was grafted onto unsaturated P(3HDD-co-3H10U), a random copolymer of 3-hydroxydodecanoate (3HDD) and 3-hydroxy-10-undecylenate (3H10U), via a thiol-ene click reaction. Enhanced hydrophilicity and thermoresponsive property of the resulted PHA-g-PNIPAm were confirmed by water contact angle studies. The biocompatibility of PHA-g-PNIPAm was comparable to poly-3-hydroxybutyrate (PHB). The graft copolymer PHA-g-PNIPAm based on biopolyester PHA could be a promising material for biomedical applications.

The detrimental effects of micro-and nano-plastics on digestive system: An overview of oxidative stress-related adverse outcome pathway.

With the massive manufacture and use of plastics, plastic pollution-related environmental impacts have raised great concern in recent years. As byproducts of plastic fragmentation and degradation, microplastics (MPs) and nanoplastics (NPs) have been identified as novel pollutants that posed a threat to the ecosystem and humans. Since MPs/NPs could be transported via the food chain and retained in the water, the digestive system should be one of the major targets of MPs/NPs-related toxicity. Although considerable evidence has supported the digestive toxicity of MPs/NPs, the proposed mechanisms remained ambiguous due to the variety of study types, models, and endpoints. This review provided a mechanism-based perspective on MPs/NPs-induced digestive effects by adopting the adverse outcome pathway framework as a promising tool. The overproduction of reactive oxygen species was identified as the molecular initiating event in MPs/NPs-mediated injury to the digestive system. A series of detrimental effects including oxidative stress, apoptosis, inflammation, dysbiosis, and metabolic disorders were summarized as key events. Finally, the occurrence of these effects eventually led to an adverse outcome, suggesting a possible increase in the incidence of digestive morbidity and mortality.

Zwitterionic microgel preservation platform for circulating tumor cells in whole blood specimen.

The immediate processing of whole blood specimen is required in circulating tumor cell-based liquid biopsy. Reliable blood specimen stabilization towards preserving circulating tumor cells can enable more extensive geographic sharing for precise rare-cell technology, but remains challenging due to the fragility and rarity of circulating tumor cells. Herein, we establish a zwitterionic magnetic microgel platform to stabilize whole blood specimen for long-term hypothermic preservation of model circulating tumor cells. We show in a cohort study of 20 cancer patients that blood samples can be preserved for up to 7 days without compromising circulating tumor cell viability and RNA integrity, thereby doubling the viable preservation duration. We demonstrate that the 7-day microgel-preserved blood specimen is able to reliably detect cancer-specific transcripts, similar to fresh blood specimens, while there are up/down expression regulation of 1243 genes in model circulating tumor cells that are preserved by commercial protectant. Mechanistically, we find that the zwitterionic microgel assembly counters the cold-induced excessive reactive oxygen species and platelet activation, as well as extracellular matrix loss-induced cell anoikis, to prevent circulating tumor cell loss in the whole blood sample. The present work could prove useful for the development of blood-based noninvasive diagnostics.

Evaluation of nanoplastics toxicity in the soil nematode Caenorhabditis elegans by iTRAQ-based quantitative proteomics.

Plastic pollution is recognized as a major threat to ecosystems in the 21st century. Large plastic objects undergo biotic and abiotic degradation to generate micro- and nano-sized plastic pieces. Despite tremendous efforts to evaluate the adverse effects of microplastics, a comprehensive understanding of the toxicity of nanoplastics remains elusive, especially at the protein level. To this end, we used isobaric-tag-for-relative-and-absolute-quantitation-based quantitative proteomics to investigate the proteome dynamics of the soil nematode Caenorhabditis elegans in response to exposure to 100 nm polystyrene nanoplastics (PS-NPs). After 48 h of exposure to 0.1, 1, or 10 mg/L PS-NPs, 136 out of 1684 proteins were differentially expressed and 108 of these proteins were upregulated. These proteins were related to ribosome biogenesis, translation, proteolysis, kinases, protein processing in the endoplasmic reticulum, and energy metabolism. Remarkably, changes in proteome dynamics in response to exposure to PS-NPs were consistent with the phenotypic defects of C. elegans. Collectively, our findings demonstrate that disruption of proteome homeostasis is a biological consequence of PS-NPs accumulation in C. elegans, which provides insights into the molecular mechanisms underlying the toxicology of nanoplastics.

A zwitterionic cellulose-based skin sensor for the real-time monitoring and antibacterial sensing wound dressing.

Wound infection can induce inflammation and impede wound healing, being a major challenge in wound care management. A household device that can monitor infection in real time, prevent bacterial, and promote wound healing is highly desired but still rarely investigated. In this work, a novel zwitterionic cellulose-based hydrogel that enables continuously real-time monitoring and pro-healing of infected wound is designed. It is based on interpenetrating polymeric networks, including zwitterionic covalent bond network and physical bond network of carboxymethyl cellulose (CMC) with Ag+via metal-coordination interactions. When used as a sensing dressing, it is developed to exhibit pH-responsive and temperature-responsive properties for assessment of wound infection. Moreover, Ag+ can be released from carboxyl groups of CMC in response to the decrease of pH, killing bacteria and promoting wound healing. This zwitterionic carboxymethyl cellulose-based hydrogel sensor opens new avenues for domestic real-time monitoring and pro-healing of infected wound.

Cardiovascular toxicity assessment of polyethylene nanoplastics on developing zebrafish embryos.

Environmental exposure to nanoplastics is inevitable as the application of nanoplastics in our daily life is more and more extensively. So, the adverse effects of nanoplastics on human health are also gaining greater concerns. However, the subsequent toxicological response to nanoplastics, especially on cardiovascular damage was still largely unknown. In this regard, the evaluation of cardiovascular effects of nanoplastics was performed in zebrafish embryos. The results indicated that the no observed adverse effect level (NOAEL) of nanoplastics is 50 µg/mL. The pericardial toxicity and hemodynamic changes were assessed by Albino (melanin allele) mutant zebrafish line. Severe pericardial edema was observed in zebrafish embryos after exposure to nanoplastics. At the concentration higher than NOAEL, nanoplastics significantly decreased the cardiac output (CO) and blood flow velocity. The fluorescence images manifested that the nanoplastics could inhibit the subintestinal angiogenesis of transgenic zebrafish embryos line Tg (fli-1: EGFP), which might disturb the cardiovascular formation and development. The resulting vascular endothelial dysfunction and hypercoagulable state of circulating blood further accelerated thrombosis. Reactive oxidative stress (ROS) and systemic inflammation were also found in Wild AB and Tg (mpo: GFP) zebrafish embryos, respectively. We also found many neutrophils recruiting in the tail vein where the zebrafish embryo thrombosis occurred. Our data suggested that nanoplastics could trigger the cardiovascular toxicity in zebrafish embryos, which could provide an essential clue for the safety assessment of nanoplastics.

Advanced biomaterials in cell preservation: Hypothermic preservation and cryopreservation.

Cell-based medicine has made great advances in clinical diagnosis and therapy for various refractory diseases, inducing a growing demand for cell preservation as support technology. However, the bottleneck problems in cell preservation include low efficiency and poor biocompatibility of traditional protectants. In this review, cell preservation technologies are categorized according to storage conditions: hypothermic preservation at 1 °C~35 °C to maintain short-term cell viability that is useful in cell diagnosis and transport, while cryopreservation at -196 °C~-80 °C to maintain long-term cell viability that provides opportunities for therapeutic cell product storage. Firstly, the background and developmental history of the protectants used in the two preservation technologies are briefly introduced. Secondly, the progress in different cellular protection mechanisms for advanced biomaterials are discussed in two preservation technologies. In hypothermic preservation, the hypothermia-induced and extracellular matrix-loss injuries to cells are comprehensively summarized, as well as the recent biomaterials dependent on regulation of cellular ATP level, stabilization of cellular membrane, balance of antioxidant defense system, and supply of mimetic ECM to prolong cell longevity are provided. In cryopreservation, cellular injuries and advanced biomaterials that can protect cells from osmotic or ice injury, and alleviate oxidative stress to allow cell survival are concluded. Last, an insight into the perspectives and challenges of this technology is provided. We envision advanced biocompatible materials for highly efficient cell preservation as critical in future developments and trends to support cell-based medicine. STATEMENT OF SIGNIFICANCE: Cell preservation technologies present a critical role in cell-based applications, and more efficient biocompatible protectants are highly required. This review categorizes cell preservation technologies into hypothermic preservation and cryopreservation according to their storage conditions, and comprehensively reviews the recently advanced biomaterials related. The background, development, and cellular protective mechanisms of these two preservation technologies are respectively introduced and summarized. Moreover, the differences, connections, individual demands of these two technologies are also provided and discussed.

Universal Intraductal Surface Antifouling Coating Based on an Amphiphilic Copolymer.

Surface modification on the inner wall of medical or industrial polymeric catheters with a high length/diameter ratio is highly desired. Herein, a universal and facile method based on an amphiphilic copolymer was developed to immobilize an intraductal surface antifouling coating for a variety of polymeric catheters. A fouling-repelled thin layer was formed by swelling-driven adsorption via directly perfusing an amphiphilic copolymer [polyvinylpyrrolidone-polydimethylsiloxane-polyvinylpyrrolidone (PVP-PDMS-PVP)] solution into catheters. In this copolymer, hydrophobic PDMS was embedded into a shrinking cross-linked network of catheters; also, PVP segments migrated to the surface under driving water to form a hydrophilic antifouling coating. Moreover, because of the coordination between I2 and pyrrolidone of PVP, the copolymer-modified intraductal surface was then infused with aqueous I2 to form the PVP-I2 complex, endowing this coating with bactericidal activity. Notably, diverse catheters with arbitrary shapes (circular, rectangular, triangular, and hexagonal) and different components (silicone, polyurethane, and polyethylene) were also verified to work using this interfacial interpenetration strategy. The findings in this work provide a new avenue toward facile and universal fabrication of intraductal surface antifouling catheters, creating a superior option for decreasing the consumable costs in industrial production and alleviating the pain of replacing catheters for patients.

Catalytic conversion of enzymatic hydrolysis lignin into cycloalkanes over a gamma-alumina supported nickel molybdenum alloy catalyst.

The efficient depolymerization and hydrodeoxygenation of enzymatic hydrolysis lignin are achieved in cyclohexane solvents over a gamma-alumina supported nickel molybdenum alloy catalyst in a single step. Under initial 3 MPa hydrogen at 320 °C, the highest overall cycloalkane yield of 104.4 mg/g enzymatic hydrolysis lignin with 44.4 wt% selectivity of ethyl-cyclohexane was obtained. The reaction atmosphere and temperature have significant effects on enzymatic hydrolysis lignin conversion, product type and distribution. The conversion of enzymatic hydrolysis lignin was also investigated over different nickel and molybdenum-based catalysts, and the gamma-alumina supported nickel molybdenum alloy catalyst exhibited the highest activity among those catalysts. To reveal the reaction pathways of alkylphenol hydrodeoxygenation, 4-ethylphenol was tested as a model compound. Complete conversion of 4-ethylphenol into cycloalkanes was achieved. A two-step mechanism of 4-ethylphenol dihydroxylation - hydrogenation is proposed, in which the benzene ring saturation is deemed as the rate-determining step.

A Zwitterionic-Aromatic Motif-Based ionic skin for highly biocompatible and Glucose-Responsive sensor.

Electronic skins that can sense external stimuli have been of great significance in artificial intelligence and smart wearable devices in recent years. However, most of current skin materials are unable to achieve high biocompatibility and anti-bacterial activity, which are particularly critical to wearable sensors for neonatal/premature monitoring or tissue-interfaced biosensors (such as electronic wound dressing and smart contact lens). Herein, a zwitterionic-aromatic motif-based conductive hydrogel with electrostatic and π-π interactions is designed for the development of ionic skin sensors. The hydrogel possesses high biocompatibility, anti-bacterial activity, especially glucose-responsive property which has not been achieved by previous ionic skins. Due to its unique molecular design, the zwitterionic-aromatic skin sensor exhibits excellent mechanical properties (robust elasticity and large stretchability) and high-sensitive pressure detection (including a gentle finger touch, small water droplets, and vocal cord vibration). More importantly, aromatic motives in phenylboronic acid segments endow the skin with glucose-responsive property. This skin sensor not only shows great potential in wearable e-skins, but also possesses a promising property for the tissue-interfaced and implantable continuous-glucose-monitor biosensors such as smart wound dressing with a high demand of biocompatibility.

Self-Powered and Self-Functional Cotton Sock Using Piezoelectric and Triboelectric Hybrid Mechanism for Healthcare and Sports Monitoring.

Wearable devices rely on hybrid mechanisms that possess the advantages of establishing a smarter system for healthcare, sports monitoring, and smart home applications. Socks with sensing capabilities can reveal more direct sensory information on the body for longer duration in daily life. However, the limitation of suitable materials for smart textile makes the development of multifunctional socks a major challenge. In this paper, we have developed a self-powered and self-functional sock (S2-sock) to realize diversified functions including energy harvesting and sensing various physiological signals, i.e., gait, contact force, sweat level, etc., by hybrid integrating poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS)-coated fabric triboelectric nanogenerator (TENG) and lead zirconate titanate (PZT) piezoelectric chips. An output power of 1.71 mW is collected from a PEDOT:PSS-coated sock with mild jumping at 2 Hz and load resistance of 59.7 MΩ. The study shows that cotton socks worn daily can potentially be a power source for enabling self-sustained socks comprising wireless transmission modules and integrated circuits in the future. We also investigate the influences of environmental humidity, temperature, and weight variations and verify that our S2-sock can successfully achieve walking pattern recognition and motion tracking for smart home applications. On the basis of the sensor fusion concept, the outputs from TENG and PZT sensors under exercise activities are effectively merged together for quick detection of the sweat level. By leveraging the hybrid S2-sock, we can achieve more functionality in the applications of foot-based energy harvesting and monitoring the diversified physiological signals for healthcare, smart homes, etc.

Microbial Poly-3-Hydroxybutyrate (PHB) as a Feed Additive for Fishes and Piglets.

The large-scale use of petrochemical-based plastics is damaging our environment. Discarded plastics are harmful to both marine and land animals, sometimes causing death when ingested. Biodegradable plastics have gained attentions from the public and the academia to reduce environmental burdens. Poly-3-hydroxybutyrate (PHB), the simplest and the best-studied bioplastic member of the polyhydroxyalkanoate (PHA) family synthesized by many bacteria, has been studied as a feed additive for large yellow croaker fish and weaned piglets. The fish grow faster and gain more weight when 1% and 2% PHB is added as a feed additive, accompanied by increased survival rates. Weaned piglets are found to grow normally and showed no significant change in average daily weight gains, average daily feed intakes, feed efficiency, and organ developments when 0.5% PHB is added to the feed. It can therefore be concluded that biodegradable and biocompatible PHB is not harmful as a feed additive for marine large yellow croakers and sensitive weaned piglets. PHB therefore holds great promise as a plastic that combines biodegradability and biocompatibility with good tolerability as a feed supplement for animals.

Hydrolysis of cellulose using cellulase physically immobilized on highly stable zirconium based metal-organic frameworks.

Developing a new cellulase-MOF composite system with enhanced stability and reusability for cellulose hydrolysis was aimed. Physical adsorption strategy was employed to fabricate two cellulase composites, and the activity of composite was characterized by hydrolysis of carboxymethyl cellulose. The NH2 functionalized UiO-66-NH2 MOF exhibited higher protein loading than the precursor UiO-66, due to the extra anchor sites of NH2 groups. The immobilized cellulase showed enhanced thermostability, pH tolerance and lifetime. The maximum activity attained at 55 °C could be kept 85% when used at 80 °C, and the residual activities were 72% after ten cycles and 65% after 30 days storage. The abundant NH2 and COOH groups of MOF adsorb cellulase and enhance its stability, and the resulted heterogeneity offered the opportunity of recovering composite via mild centrifuge. The findings suggest the promising future of developing cellulase-MOF composite with ultrahigh activities and stabilities for practical application.

Engineering Halomonas bluephagenesis TD01 for non-sterile production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate).

Poly(3-hydroxybutyrate-co-4-hydroxybutyrate), short as P(3HB-co-4HB), was successfully produced by engineered Halomonas bluephagenesis TD01 grown in glucose and γ-butyrolactone under open non-sterile conditions. Gene orfZ encoding 4HB-CoA transferase of Clostridium kluyveri was integrated into the genome to achieve P(3HB-co-4HB) accumulation comparable to that of strains encoding orfZ on plasmids. Fed-batch cultivations conducted in 1-L and 7-L fermentors, respectively, resulted in over 70g/L cell dry weight (CDW) containing 63% P(3HB-co-12mol% 4HB) after 48h under non-sterile conditions. The processes were further scaled up in a 1000-L pilot fermentor to reach 83g/L CDW containing 61% P(3HB-co-16mol% 4HB) in 48h, with a productivity of 1.04g/L/h, again, under non-sterile conditions. The elastic P(3HB-co-16mol% 4HB) shows an elongation at break of 1022±43%. Results demonstrate that the engineered Halomonas bluephagenesis TD01 is a suitable industrial strain for large scale production under open non-sterile conditions.

Irgm1 is required for the inflammatory function of M1 macrophage in early experimental autoimmune encephalomyelitis.

The classically activated (M1) macrophage has been shown to play an indispensable role in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). However, most studies focus on the effect of macrophage on CNS demyelination of EAE; whether the M1 macrophage participates in early EAE and the molecular mechanism underlying remains unclear. Here, we showed that the immunity-related GTPase family member 1 (Irgm1), also known as LRG-47, was expressed in M1 macrophages of draining lymph nodes (dLNs) from C57BL/6 mice with early EAE, and the IRGM1 heterozygote substantially reduced M1 macrophage accumulation in dLNs and spleen of the primary EAE stage. In vitro silence of IRGM1 in M1 macrophages impaired NOS2 expression and inflammatory cytokine release. We also found that IRGM1 knockout (Irgm1-/-) in M1 macrophages increased Akt activation but attenuated NF-κB p65 activation, which may reveal Irgm1-mediated mechanisms of action. Interestingly, macrophage depletion in vivo inhibited Th1/Th17 differentiation in the spleen and promoted regulatory T cell (Treg) polarization in dLNs at 7 d postimmunization (dpi). Moreover, we observed that M1 macrophages in vitro promoted Th1/Th17 differentiation, which was reversed by treatment with IRGM1 small interfering RNA (siRNA), anti-TNF-α, or anti-IL-1ß mAb. These results suggest that the M1 macrophage may promote Th1/Th17 cell differentiation during the early EAE, and the proinflammatory function of M1 cells requires Irgm1.

Designing colon-specific delivery systems for anticancer drug-loaded nanoparticles: an evaluation of alginate carriers.

Incorporation of drug-loaded nanoparticles (NPs) in colon-specific delivery systems shows potential for raising local drug concentrations, tumor targeting and improving chemotherapy. Alginate microcapsules (15-80 µm diameter) containing insoluble Eudragit(®) RS NPs as models were characterized precisely in terms of NP loading and release kinetics. High NP loading (22%, w/w of the dried microcapsules) combined with negligible release in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) suggested that high concentrations of NPs could be transported to the colon. However, NP aggregation was confirmed at extremely low concentration (0.0003%, w/v) in alginate solution (0.007%, w/v) and after release from alginate microcapsules. Indomethacin, a model anticolorectal cancer drug, was encapsulated in pH-responsive Eudragit(®) S100 NPs (116 nm, 5%, w/w drug loading) using the nanoprecipitation method. Approximately 90% of the drug load was released from the NPs in SGF and SIF before transfer to simulated colon fluid (SCF). However, incorporation of NPs in 2 mm alginate pellets resulted in a significantly higher fraction of the drug load (around 60%) being available for release in SCF. Delivery of isolated NPs to the colon for interaction with and uptake by cancer cells requires elimination of NP-excipient interactions that promote NP aggregation. NP-loaded alginate carriers, meanwhile, offer a promising strategy for delivery of anticancer drugs to tumor sites in the colon and reducing systemic side effects.