PEDOT-Integrated Fish Swim Bladders as Conductive Nerve Conduits.

Advanced artificial nerve conduits offer a promising alternative for nerve injury repair. Current research focuses on improving the therapeutic effectiveness of nerve conduits by optimizing scaffold materials and functional components. In this study, a novel poly(3,4-ethylenedioxythiophene) (PEDOT)-integrated fish swim bladder (FSB) is presented as a conductive nerve conduit with ordered topology and electrical stimulation to promote nerve regeneration. PEDOT nanomaterials and adhesive peptides (IKVAV) are successfully incorporated onto the decellularized FSB substrate through pre-coating with polydopamine. The obtained PEDOT/IKVAV-integrated FSB substrate exhibits outstanding mechanical properties, high electrical conductivity, stability, as well as excellent biocompatibility and bioadhesive properties. In vitro studies confirm that the PEDOT/IKVAV-integrated FSB can effectively facilitate the growth and directional extension of pheochromocytoma 12 cells and dorsal root ganglion neurites. In addition, in vivo experiments demonstrate that the proposed PEDOT/IKVAV-integrated FSB conduit can accelerate defective nerve repair and functional restoration. The findings indicate that the FSB-derived conductive nerve conduits with multiple regenerative inducing signals integration provide a conducive milieu for nerve regeneration, exhibiting great potential for repairing long-segment neural defects.

Association Between Different Types of Physical Activity and Hepatic Steatosis and Liver Fibrosis: A Cross-Sectional Study Based on NHANES.

BACKGROUND AND AIMS: Many studies have shown a link between physical activity (PA) and nonalcoholic fatty liver disease (NAFLD). However, more research is needed to investigate the relationship between different types of PA and NAFLD. This study aimed to explore the potential link between different types of PA, hepatic steatosis, and liver fibrosis. STUDY: A cross-sectional study was conducted using the data set from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. A multiple linear regression model was used to examine the linear relationship between different types of PA, the controlled attenuation parameter (CAP), and liver stiffness measurement (LSM). In addition, smoothing curve fitting and threshold effect analysis were used to depict their nonlinear relationship. RESULTS: This study involved 5933 adults. Multiple linear regression analysis revealed a significantly negative correlation between leisure-time PA and CAP, while the relationship between occupation-related PA, transportation-related PA, and CAP was not significant. Subgroup analysis further revealed that leisure-time PA was significantly negatively correlated with CAP in women and younger age groups (under 60 y old), while the relationship was not significant in men and older age groups. In addition, there was a significant negative correlation between leisure-time PA and liver fibrosis in men. CONCLUSIONS: Leisure-time PA can prevent hepatic steatosis, and women and young people benefit more. Occupation-related PA is not associated with hepatic steatosis and cannot replace leisure-time PA. In men, increasing leisure-time PA is more effective in preventing liver fibrosis.

Camellia oil exhibits anti-fatigue property by modulating antioxidant capacity, muscle fiber, and gut microbial composition in mice.

Camellia seed oil (CO) has high nutritional value and multiple bioactivities. However, the specific anti-fatigue characteristics and the implied mechanism of CO have not yet been fully elucidated. Throughout this investigation, male C57BL/6J mice, aged 8 weeks, underwent exhaustive exercise with or without CO pretreatment (2, 4, and 6 mL/kg BW) for 28 days. CO could extend the rota-rod and running time, reduce blood urea nitrogen levels and serum lactic acid, and increase muscle and hepatic glycogen, adenosine triphosphate, and anti-oxidative indicators. Additionally, CO could upregulate the mRNA and Nrf2 protein expression levels, as well as enhance the levels of its downstream antioxidant enzymes and induce the myofiber-type transformation from fast to slow and attenuate the gut mechanical barrier. Moreover, CO could ameliorate gut dysbiosis by reducing Firmicutes to Bacteroidetes ratio at the phylum level, increasing the percentage of Alistipes, Alloprevotella, Lactobacillus, and Muribaculaceae, and decreasing the proportion of Dubosiella at the genus level. In addition, specific bacterial taxa, which were altered by CO, showed a significant correlation with partial fatigue-related parameters. These findings suggest that CO may alleviate fatigue by regulating antioxidant capacity, muscle fiber transformation, gut mechanical barrier, and gut microbial composition in mice. PRACTICAL APPLICATION: Our study revealed that camellia seed oil (CO) could ameliorate exercise-induced fatigue in mice by modulating antioxidant capacity, muscle fiber, and gut microbial composition in mice. Our results promote the application of CO as an anti-fatigue functional food that targets oxidative stress, myofiber-type transformation, and microbial community.

Unveiling the intricate causal nexus between pancreatic cancer and peripheral metabolites through a comprehensive bidirectional two-sample Mendelian randomization analysis.

Aim: Pancreatic cancer (PC) is a devastating malignancy characterized by its aggressive nature and poor prognosis. However, the relationship of PC with peripheral metabolites remains not fully investigated. The study aimed to explore the causal linkage between PC and peripheral metabolite profiles. Methods: Employing publicly accessible genome-wide association studies (GWAS) data, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis. The primary analysis employed the inverse-variance weighted (IVW) method. To address potential concerns about horizontal pleiotropy, we also employed supplementary methods such as maximum likelihood, weighted median, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO). Results: We ascertained 20 genetically determined peripheral metabolites with causal linkages to PC while high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL) particles accounted for the vast majority. Specifically, HDL particles exhibited an elevated PC risk while VLDL particles displayed an opposing pattern. The converse MR analysis underscored a notable alteration in 17 peripheral metabolites due to PC, including branch chain amino acids and derivatives of glycerophospholipid. Cross-referencing the bidirectional MR results revealed a reciprocal causation of PC and X-02269 which might form a self-perpetuating loop in PC development. Additionally, 1-arachidonoylglycerophosphocholine indicated a reduced PC risk and an increase under PC influence, possibly serving as a negative feedback regulator. Conclusion: Our findings suggest a complex interplay between pancreatic cancer and peripheral metabolites, with potential implications for understanding the etiology of pancreatic cancer and identifying novel early diagnosis and therapeutic targets. Moreover, X-02269 may hold a pivotal role in PC onset and progression.

Maternal Vitamin A deficiency during pregnancy and lactation induced damaged intestinal structure and intestinal flora homeostasis in offspring mice.

The small intestine serves as the first channel of dietary Vitamin A (VA) and the unique organ of VA absorption and metabolism. However, there have not been extensive investigations on the exact mechanisms within VA-related changes in intestinal metabolic disorders. This research is designed to analyze whether and how VA affects intestinal metabolic phenotypes. Male C57BL/6 mice after weaning were randomly fed a VA control diet (VAC) or a VA-deficient diet (VAD) during the entire pregnancy and lactation process. After a total of 11 weeks, cohorts of VA deprived were next fed to a VA control diet (VAD-C) for another 8 weeks. The concentration of retinol was measured by a high-performance liquid chromatography system. The 16S gene sequencing was used to evaluate the intestinal microbiota changes. Through the use of histological staining, western blots, quantitative PCR, and enzyme-linked immunosorbent assays, the intestinal morphology, inflammatory factors, and intestinal permeability were all evaluated. Following the decrease of the tissue VA levels, VAD mice show a decrease in tissue VA levels, community differences, and the richness and diversity of intestinal microbiota. VAD diet-driven changes occur in intestinal microbiota, accompanied by a higher mRNA expression of intestinal inflammatory cytokines and an increase in intestinal permeability. As dietary VA is reintroduced into VAD diet-fed mice, the tissue VA levels, inflammatory response, and intestinal homeostasis profiles are all restored, which are similar to those found after the occurrence of VA-controlled changes within intestinal microbiota. VA deficiency caused the imbalance of intestinal metabolic phenotypes through a mechanism involving changes in intestinal microbiota. It is thought that intestinal microbiota metabolic influences represent a new salient and additional mechanism, which can be used as a new method to achieve the onset and treatment of the effect of VAD on intestinal homeostasis impairment.

The association between character strengths and job crafting among nurses in tertiary hospitals: A cross-sectional survey.

AIM: This study was to investigate the association between character strengths and job crafting among nurses in tertiary hospitals in China. DESIGN: A cross-sectional survey was conducted. METHODS: From February 2021 to April 2021, 1006 nurses from four tertiary hospitals in China were recruited to complete a series of online questionnaires assessing their job crafting and character strengths. The analysis was conducted using structural equation modelling (SEM). RESULTS: The mean scores for task crafting, cognitive crafting and relationship crafting were 3.19 ± 0.58, 3.50 ± 0.55 and 3.58 ± 0.51. There is a moderate level of job crafting and character strengths among Chinese nurses working at tertiary hospitals. Additionally, it was revealed by the SEM that character strengths contributed to 81% of the variance of job crafting and job crafting was positively correlated with nurses' character strengths. The study shows the need to develop nurses' character strengths to enhance job crafting behaviours.

Scalable Production of Biomedical Microparticles via High-Throughput Microfluidic Step Emulsification.

Drug microcarriers are widely used in disease treatment, and microfluidics is well established in the preparation of microcarrier particles. A proper design of the microfluidic platform toward scalable production of drug microcarriers can extend its application values in wound healing, where large numbers of microcarriers are required. Here, a microfluidic step emulsification method for the preparation of monodisperse droplets is presented. The droplet size depends primarily on the microchannel depth rather than flow rate, making the system robust for high-throughput production of droplets and hydrogel microparticles. Based on this platform, basic fibroblast growth factor (bFGF) is uniformly encapsulated in the microparticles, and black phosphorus (BP) is incorporated for controllable release via near-infrared (NIR) stimulation. The microparticles serve as drug carriers to be applied to the wound site, inducing angiogenesis and collagen deposition, thereby accelerating wound repair. These results indicate that the step emulsification technique provides a promising solution to scalable production of drug microcarriers for wound healing as well as tissue regeneration.

The CLOCK protein regulates insulin secretion related with L-type calcium channels in rat pancreatic beta cells.

BACKGROUND: Circadian locomotor output cycles kaput protein (CLOCK) plays a crucial role in glucose homeostasis and controlling insulin secretion. However, the mechanism of the CLOCK regulating rhythmic insulin secretion has not been fully understood. METHODS: Rhythmic expression of the CLOCK in rat pancreatic beta cell was detected. INS-1 cells were transfected with siRNAs to knockdown the CLOCK before the cells were incubated with different concentrations of glucose. Insulin secretion was analyzed by ELISA method. Expression of the L-type calcium channel protein (Cav1.2, Cacna1c) was determined both in the CLOCK-knockdown cells and the control cells. Calcium influx was probed by fluorescent. Chromatin immunoprecipitation (ChIP) test and dual-luciferase reporter gene experiments were applied to verify the relationship between the CLOCK and Cav1.2. RESULTS: The CLOCK is abundantly expressed in rat pancreatic beta cells. Transcription level of the CLOCK showed rhythmicity in the beta cells. Compared to the control group, insulin release was significantly impaired with 25 mM glucose incubation in the CLOCK-knockdown group, but not showed with 2.5 mM glucose incubation. The expression of Cav1.2 and the influx of calcium were significantly decreased in the CLOCK-knockdown group with 25 mM glucose incubation. ChIP test indicted that the CLOCK bound to -444∼-454 region of the Cacna1c promoter of the INS-1 cells, but the binding was significantly reduced following the CLOCK-knockdown. Luciferase experiment was in accordance with the finding of ChIP. CONCLUSIONS: The CLOCK mediating Cav1.2 expression may point out a potential pathway of circadian rhythm affecting insulin secretion.

Plasma Metabolomics Profiling of Metabolic Pathways Affected by Major Depressive Disorder.

Background: Major depressive disorder (MDD) is a common disease which is complicated by metabolic disorder. Although MDD has been studied relatively intensively, its metabolism is yet to be elucidated. Methods: To profile the global pathophysiological processes of MDD patients, we used metabolomics to identify differential metabolites and applied a new database Metabolite set enrichment analysis (MSEA) to discover dysfunctions of metabolic pathways of this disease. Hydrophilic metabolomics were applied to identify metabolites by profiling the plasma from 55 MDD patients and 100 sex-, gender-, BMI-matched healthy controls. The metabolites were then analyzed in MSEA in an attempt to discover different metabolic pathways. To investigate dysregulated pathways, we further divided MDD patients into two cohorts: (1) MDD patients with anxiety symptoms and (2) MDD patients without anxiety symptoms. Results: Metabolites which were hit in those pathways correlated with depressive and anxiety symptoms. Altogether, 17 metabolic pathways were enriched in MDD patients, and 23 metabolites were hit in those pathways. Three metabolic pathways were enriched in MDD patients without anxiety, including glycine and serine metabolism, arginine and proline metabolism, and phenylalanine and tyrosine metabolism. In addition, L-glutamic acid was positively correlated with the severity of depression and retardation if hit in MDD patients without anxiety symptoms. Conclusions: Different kinds of metabolic pathophysiological processes were found in MDD patients. Disorder of glycine and serine metabolism was observed in both MDD patients with anxiety and those without.

Plasma metabolites were associated with spatial working memory in major depressive disorder.

ABSTRACT: Major depressive disorder (MDD) is a common disease with both affective and cognitive disorders. Alterations in metabolic systems of MDD patients have been reported, but the underlying mechanisms still remains unclear. We sought to identify abnormal metabolites in MDD by metabolomics and to explore the association between differential metabolites and neurocognitive dysfunction.Plasma samples from 53 MDD patients and 83 sex-, gender-, BMI-matched healthy controls (HCs) were collected. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was then used to detect metabolites in those samples. Two different algorithms were applied to identify differential metabolites in 2 groups. Of the 136 participants, 35 MDD patients and 48 HCs had completed spatial working memory test. Spearman rank correlation coefficient was applied to explore the relationship between differential metabolites and working memory in these 2 groups.The top 5 metabolites which were found in sparse partial least squares-discriminant analysis (sPLS-DA) model and random forest (RF) model were the same, and significant difference was found in 3 metabolites between MDD and HCs, namely, gamma-glutamyl leucine, leucine-enkephalin, and valeric acid. In addition, MDD patients had higher scores in spatial working memory (SWM) between errors and total errors than HCs. Valeric acid was positively correlated with working memory in MDD group.Gamma-glutamyl leucine, leucine-enkephalin, and valeric acid were preliminarily proven to be decreased in MDD patients. In addition, MDD patients performed worse in working memory than HCs. Dysfunction in working memory of MDD individuals was associated with valeric acid.

Isoacteoside attenuates acute kidney injury induced by severe acute pancreatitis.

Severe acute pancreatitis (SAP) is a common acute abdominal disease accompanied by systemic inflammatory response syndrome, which may be complicated by acute kidney injury (AKI). Isoacteoside (ISO) is the active ingredient of Monochasma savatieri Franch. ex Maxim and has been reported to have anti­inflammatory activities. The present study detected the effects of ISO on AKI induced by SAP in rat models, and the underlying mechanism. The optimum dose of ISO for treatment of AKI induced by SAP was determined. The serum levels of TNF­α and IL­6 were estimated using an ELISA. Kidney injury was evaluated by histopathological examination, and the expression levels of nitric oxide were also detected. The expression levels of Toll­like receptor 4 (TLR4) and NF­κB p65 were measured by immunohistochemistry and western blotting. The results revealed that ISO may serve a critical role in ameliorating AKI induced by SAP. These effects may be associated with the TLR4/NF­κB signaling pathway.

An Expanded Gene Catalog of Mouse Gut Metagenomes.

High-quality and comprehensive reference gene catalogs are essential for metagenomic research. The rather low diversity of samples used to construct existing catalogs of the mouse gut metagenome limits the numbers of identified genes in existing catalogs. We therefore established an expanded catalog of genes in the mouse gut metagenome (EMGC) containing >5.8 million genes by integrating 88 newly sequenced samples, 86 mouse gut-related bacterial genomes, and 3 existing gene catalogs. EMGC increases the number of nonredundant genes by more than 1 million genes compared to the so-far most extensive catalog. More than 60% of the genes in EMGC were assigned to Bacteria, with 54.20% being assigned to a phylum and 35.33% to a genus, while 30.39% were annotated at the KEGG orthology level. Nine hundred two metagenomic species (MGS) assigned to 122 taxa are identified based on the EMGC. The EMGC-based analysis of samples from groups of mice originating from different animal providers, housing laboratories, and genetic strains substantiated that diet is a major contributor to differences in composition and functional potential of the gut microbiota irrespective of differences in environment and genetic background. We envisage that EMGC will serve as a valuable reference data set for future metagenomic studies in mice.IMPORTANCE We established an expanded gene catalog of the mouse gut metagenome not only to increase the sample size compared to that in existing catalogs but also to provide a more comprehensive reference data set of the mouse gut microbiome for bioinformatic analysis. The expanded gene catalog comprises more than 5.8 million unique genes, as well as a wide range of taxonomic and functional information. Particularly, the analysis of metagenomic species with the expanded gene catalog reveals a great novelty of mouse gut-inhabiting microbial species. We envisage that the expanded gene catalog of the mouse gut metagenome will serve as a valuable bioinformatic resource for future gut metagenomic studies in mice.

Single symbiotic cell transcriptome sequencing of coral.

Zooxanthellae and coral can form an intracellular symbiotic system. Yet, little is known about the molecular mechanism underlying this symbiosis. In this study, we characterized the symbiosis based on analyses of gene expression at the single-cell level. Among 9110 single coral cells, we identified 4871 symbiotic cells based on the detection of both coral and zooxanthellae gene transcripts within a single cell. Using the bioinformatics tool Seurat, symbiotic cells were further clustered into five groups, 52 genes exhibited differential expression between groups. We proposed an index called the "symbiosis index", to indicate the degree of gene expression of both species in a single symbiotic cell. Interestingly, the index differed distinctly among the five groups. The symbiosis index was highly correlated with the expression of the coral gene gfas1.m1.6761 (ANKRD40), which encodes ankyrin repeat domain-containing protein 40 and is involved in DNA replication (r = 0.76). Two metabolism-related genes, DAGLA and betaGlu, were highly expressed in cells with a high symbiosis index. Four zooxanthellae genes, PRPF19, ATRN, aAA-ATPases and AK812-SmicGene44833, exhibited substantial changes in expression levels when zooxanthellae lived within coral. A trajectory analysis suggested that cells with a higher symbiosis index may be derived from those with a lower index during coral colony development. Taken together, our results provide evidence for zooxanthellae residing within coral, forming a symbiotic system. The symbiosis index is an effective indicator of different cell groups, with lineage relationships among groups. Additionally, we identified specific genes that exhibit expression changes in the symbiotic system.

Immunotherapeutic silk inverse opal particles for post-surgical tumor treatment.

Recurrence of malignant tumor after surgical resection is the main reason of cancer treatment failure. Here, a novel kind of silk inverse opal particles (SIOPs) for post-surgical tumor treatment is presented, and it is derived from colloid crystal bead templates by negatively replicating. Because of their abundant uniform nanopores, interconnected nanochannels and excellent biocompatibility, SIOPs could not only carry great amount of anti-tumor drugs for tumor therapy, but also could provide support for cell adhesion, proliferation and differentiation as the 3D spherical scaffolds which is beneficial to the tissue repair at resection sites. It is demonstrated that the antibody drugs could maintain their high biological activity without any influences during the preparation of SIOPs and these particles were able to enhance the therapeutic efficacy and promote tissue regeneration after surgical resection with their multifunctional features. These prominent properties indicate the great potentials of SIOPs as a promising strategy for efficient postoperative cancer therapy.

Biocompatible Self-Healing Coating Based on Schiff Base for Promoting Adhesion of Coral Cells.

Layer-by-layer self-assembly (LBL) technique is a very efficient and convenient method to modify the substrate surface. In this study, we report a self-repairing surface coating that can promote cell adhesion, especially for enhancing the adhesion of coral cells on the basal surface. The results confirmed that the modified chitosan-dialdehyde starch film based on Schiff base has good biocompatibility for common mammalian cells, such as normal human dermal fibroblasts (NHDFs) and relatively special cells (coral cells). The cytotoxicity test indicated that the optical density values of the experimental group films at 490 nm were higher than those of the control group in this study. In addition, the self-repairing coating modified by phase transition lysozyme can maintain its adhesion ability underwater for a period of time. Therefore, they have great application on substrates requiring underwater adhesion. Our results confirmed that the modified chitosan-dialdehyde starch self-healing films could provide a biocompatible coating material to promote the adhesion of normal human epidermal fibroblasts or coral cells.

Hypothermic Oxygenated Machine Perfusion Alleviates Donation After Circulatory Death Liver Injury Through Regulating P-selectin-dependent and -independent Pathways in Mice.

BACKGROUND: Hypothermic oxygenated machine perfusion (HOPE) has been shown to improve the quality of liver donation after circulatory death (DCD) compared to cold storage (CS). However, the mechanism by which HOPE works is unclear. In this study, a mouse liver HOPE system was developed to characterize the role of P-selectin in the protective effect of HOPE on DCD livers. METHODS: A warm ischemia model of the liver and an isolated perfused liver system were established to determine a suitable flow rate for HOPE. Perfusate and tissue samples from wild-type and P-selectin knockout (KO) mice were used to determine liver function, apoptosis and necrosis rates, deoxyribonucleic acid injury and oxidative stress levels, leukocyte and endothelial cell activation, and inflammatory reactions. RESULTS: A mouse liver HOPE system was successfully established. HOPE at flow rates between 0.1 and 0.5 mL/min · g were shown to have a protective effect on the DCD liver. P-selectin KO improved the quality of the DCD liver in the CS group, and reduction of P-selectin expression in the wild-type HOPE group had similar protective effects. Moreover, there was a reduction in the degree of oxidative stress and deoxyribonucleic acid injury in the P-selectin KO HOPE group compared with the P-selectin KO CS group. CONCLUSIONS: We established a mouse HOPE system and determined its suitable flow. We also proved that P-selectin deficiency alleviated DCD liver injury. HOPE protected the DCD liver through regulating P-selectin-dependent and -independent pathways.

Porous scaffolds from droplet microfluidics for prevention of intrauterine adhesion.

Severe intrauterine adhesions (IUAs) have a great negative impact on women's psychological and reproductive health. It remains a significant challenge to prevent postoperative IUAs because of the complications of various clinical preventive measures and incompatibility of uterine cavity morphology. Herein, we present a new drug-loadedporous scaffold based on a microfluidic droplet template, which combines the characteristics of the artificial biocompatible material GelMA and the natural polysaccharide material Na-alginate. By changing the containers that collect the microfluidic droplets, the porous scaffold conforming to the shape of the uterine cavity could be obtained. The porous structure, mechanical property, and flexibility impart the scaffold with compressibility and send it to the uterus through the vagina. In addition, the external-internal connected open structures could load and control the release of drugs to repair the damaged region continuously in vivo. To verify the antiadhesion and repair of drug-loaded porous scaffolds, we tested the system in the rat model of IUAs, and it was demonstrated that the system had the ability to improve neovascularization, cellularize the damaged tissue, and repair the endometrium. These features provide the drug-loaded porous scaffolds with new options for the improvement of postoperative IUAs. STATEMENT OF SIGNIFICANCE: Intrauterine adhesions are caused by various causes of damage to the endometrial basal layer, thus leading to part or entire adhesions in the cervical or uterine cavity. Clinically, various preventive measures reach the barrier effect through the physical barrier, which are difficult to further promote the repair of the damaged endometrium, and most of them have apparent side effects. This study aims to prepare compressible and biodegradable three-dimensional porous drug-loading biological scaffolds. GelMA and Na-alginate have desirable biocompatibility. The interconnect porous scaffolds, which were prepared through the combination of biomaterials and single emulsion microfluidics, not only have compressibility but also provide space for drug delivery and release. This system can further promote the repair of the endometrium while preventing adhesion.

Effect of JAK2/STAT3 signaling pathway on liver injury associated with severe acute pancreatitis in rats.

Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling constitutes one of the major pathways for cytokine signal transduction. However, the role of the JAK2/STAT3 pathway in liver injury during severe acute pancreatitis (SAP) remains unclear. The aim of this study was to investigate the role of the JAK2/STAT3 signaling pathway in liver injury after SAP. In the present study 64 male Sprague-Dawley rats were randomly divided into four groups: Control, AG490 (inhibition of JAK2), SAP and SAP with AG490. SAP was induced by retrograde infusion of 4% sodium taurocholate into the biliopancreatic duct. The activities of amylase (AMY) and liver enzymes were measured in serum. Livers and pancreas were isolated for measurements of histological damage. Blood and liver samples were taken for the measurement of TNF-α, IL-6 and IL-18 concentrations. The expression levels of JAK2 and STAT3 in liver tissue were detected by immunohistochemical staining and western blotting. The results demonstrated that amylase and liver enzymes were higher in the SAP groups compared with the control, AG490 and AG490-treated groups. The serum levels of TNF-α, IL-6 and IL-18 were effectively increased in the SAP groups, whereas they were reduced by AG490. Interestingly, JAK2 and STAT3 protein expression levels were significantly increased following induction of SAP and were significantly decreased in the AG490-pretreated groups. Administration of AG490 decreased the activity of pro-inflammatory cytokines and significantly attenuated SAP associated-liver injury in the rats. These results suggested that the mechanism may relate to the inhibition of TNF-α, IL-6 and IL-18, and inhibiting excessive JAK2 and STAT3 activation, and may play a crucial role in the liver injury associated with SAP.

Folic Acid-Functionalized Hybrid Photonic Barcodes for Capture and Release of Circulating Tumor Cells.

Recovery of circulating tumor cells (CTCs) from cancer patients by an efficient CTCs capture and release method can greatly increase their application in diagnostics and treatment of cancers. In this paper, we presented a folic acid (FA)-functionalized hybrid photonic barcode for capture and release of CTCs. The hybrid photonic barcodes were formed by two nano-ordered parts, poly(ethylene glycol) diacrylate (PEGDA) inverse opal structure for sustaining integrity and methacrylated gelatin (GelMA) gel filler for conjugating FA molecules to mediate cell capture. The nano-ordered structures of the hybrid photonic barcodes not only increased contact area, but also decreased steric hindrance among FA molecules. Thus, the topographic interaction between the barcodes and CTCs was greatly enhanced. In addition, GelMA gel was soft and extracellular matrix (ECM) alike, which was beneficial to decrease impairment to CTCs during the CTCs-barcode interaction as well as preserving their viability. Demonstrated by four CTCs types, Hela (epithelial tissue, folate receptor positive, FR+), A02 (bone marrow, FR+), Raji (lymphoid tissue, FR+), and A549 (epithelial tissue, folate receptor negative, FR-), FR+ CTCs could be captured efficiently with reliability and specificity. The captured cells could be controllably released with high viability just by quick trypsinization. The whole processes were simple and efficient. These features indicated that the FA-functionalized hybrid photonic barcodes were promising for full recovery of CTCs from cancer patients, which was important for diagnosis and treatment of cancer.