A modified orthotopic left lung transplantation model in rats.

To enhance the operability of the rat orthotopic left lung transplantation model, we implemented several improvements and meticulously detailed the procedure. One hundred and thirty-one healthy male Sprague Dawley rats, weighing between 250 and 300 g, were utilized, with 64 serving as donors, 64 as recipients, and 3 as sham controls. We employed a modified three-cuff technique for the orthotopic left lung transplantation. Notably, our modified perfusion method could prevent donor lung edema, while waist-shaped cuffs minimized suture slippage during anastomosis. Additionally, positioning the recipient rat in a slightly left-elevated supine position during anastomosis reduced tension on the lung hilum, thus mitigating the risk of vascular laceration. The introduction of a unique two-person anastomosis technique significantly reduced operation time and substantially improved success rates. Furthermore, maximizing inflation of donor lungs both during preservation and surgery minimized the occurrence of postoperative atelectasis. Various other procedural refinements contributed to the enhanced operability of our model. Sixty-four rat orthotopic left lung transplantations were performed with only one surgical failure observed. The acquisition time for donor lungs averaged (19 ± 4) minutes, while (11 ± 1) minutes were allocated for donor lung hilum anatomy and cuff installation. Recipient thoracotomy and left lung hilar anatomy before anastomosis required (24 ± 8) minutes, with anastomosis itself taking (31 ± 6) minutes. Remarkably, the survival rate at the 4-h postoperative mark stood at 96.7 %. Even six months post-operation, transplanted left rat lungs continued to exhibit proper inflation and contraction rhythms, displaying signs of chronic pathological changes. In summary, our modified rat model of orthotopic left lung transplantation demonstrates robust operability, significantly reducing surgical duration, improving operation success rates, and enhancing postoperative survival rates. Furthermore, its long-term survival capacity enables the simulation of acute and chronic disease processes following lung transplantation.

Quercetin attenuates inflammation in rosacea by directly targeting p65 and ICAM-1.

AIMS: Rosacea is an inflammatory skin disease with immune and vascular dysfunction. Although there are multiple treatment strategies for rosacea, the clinical outcomes are unsatisfactory. MAIN METHODS: Combining transcriptome data and the Connectivity Map database quercetin was identified as a novel candidate for rosacea. Next, the therapeutic efficacy of quercetin was substantiated through proteomic analyses, in vivo experiments, and in vitro assays. Additionally, the utilization of DARTS, molecular docking and experimental verification revealed the therapeutic mechanisms of quercetin. KEY FINDINGS: Treatment with quercetin resulted in the following effects: (i) it effectively ameliorated rosacea-like features by reducing immune infiltration and angiogenesis; (ii) it suppressed the expression of inflammatory mediators in HaCaT cells and HDMECs; (iii) it interacted with p65 and ICAM-1 directly, and this interaction resulted in the repression of NF-κB signal and ICAM-1 expression in rosacea. SIGNIFICANCE: We show for the first time that quercetin interacted with p65 and ICAM-1 directly to alleviated inflammatory and vascular dysfunction, suggesting quercetin is a novel, promising therapeutic candidate for rosacea.

Implementation and external validation of the Cambridge Multimorbidity Score in the UK Biobank cohort.

BACKGROUND: Patients with multiple conditions present a growing challenge for healthcare provision. Measures of multimorbidity may support clinical management, healthcare resource allocation and accounting for the health of participants in purpose-designed cohorts. The recently developed Cambridge Multimorbidity scores (CMS) have the potential to achieve these aims using primary care records, however, they have not yet been validated outside of their development cohort. METHODS: The CMS, developed in the Clinical Research Practice Dataset (CPRD), were validated in UK Biobank participants whose data is not available in CPRD (the cohort used for CMS development) with available primary care records (n = 111,898). This required mapping of the 37 pre-existing conditions used in the CMS to the coding frameworks used by UK Biobank data providers. We used calibration plots and measures of discrimination to validate the CMS for two of the three outcomes used in the development study (death and primary care consultation rate) and explored variation by age and sex. We also examined the predictive ability of the CMS for the outcome of cancer diagnosis. The results were compared to an unweighted count score of the 37 pre-existing conditions. RESULTS: For all three outcomes considered, the CMS were poorly calibrated in UK Biobank. We observed a similar discriminative ability for the outcome of primary care consultation rate to that reported in the development study (C-index: 0.67 (95%CI:0.66-0.68) for both, 5-year follow-up); however, we report lower discrimination for the outcome of death than the development study (0.69 (0.68-0.70) and 0.89 (0.88-0.90) respectively). Discrimination for cancer diagnosis was adequate (0.64 (0.63-0.65)). The CMS performs favourably to the unweighted count score for death, but not for the outcomes of primary care consultation rate or cancer diagnosis. CONCLUSIONS: In the UK Biobank, CMS discriminates reasonably for the outcomes of death, primary care consultation rate and cancer diagnosis and may be a valuable resource for clinicians, public health professionals and data scientists. However, recalibration will be required to make accurate predictions when cohort composition and risk levels differ substantially from the development cohort. The generated resources (including codelists for the conditions and code for CMS implementation in UK Biobank) are available online.

CoIn: Correlation Induced Clustering for Cognition of High Dimensional Bioinformatics Data.

Analysis of high dimensional biomedical data such as microarray gene expression data and mass spectrometry images, is crucial to provide better medical services including cancer subtyping, protein homology detection, etc. Clustering is a fundamental cognitive task which aims to group unlabeled data into multiple clusters based on their intrinsic similarities. However, for most clustering methods, including the most widely used K-means algorithm, all features of the high dimensional data are considered equally in relevance, which distorts the performance when clustering high-dimensional data where there exist many redundant variables and correlated variables. In this paper, we aim at addressing the problem of the high dimensional bioinformatics data clustering and propose a new correlation induced clustering, CoIn, to capture complex correlations among high dimensional data and guarantee the correlation consistency within each cluster. We evaluate the proposed method on a high dimensional mass spectrometry dataset of liver cancer tumor to explore the metabolic differences on tissues and discover the intra-tumor heterogeneity (ITH). By comparing the results of baselines and ours, it has been found that our method produces more explainable and understandable results for clinical analysis, which demonstrates the proposed clustering paradigm has the potential with application to knowledge discovery in high dimensional bioinformatics data.

Aquaporin-1 inhibition exacerbates ischemia-reperfusion-induced lung injury in mouse.

BACKGROUND: Ischemia-reperfusion injury (IRI), which involves severe inflammation and edema, is an inevitable feature of the lung transplantation process and leads to primary graft dysfunction (PGD). The activation of aquaporin 1 (AQP1) modulates fluid transport in the alveolar space. The current study investigated the role of AQP1 in ischemia-reperfusion (IR)-induced lung injury. METHODS: A mouse model of lung IR was established by clamping the left lung hilar for 1 h and released for reperfusion for 24 h. The AQP1 inhibitor acetazolamide (AZA) was administered 3 days before lung ischemia with a dose of 100 mg/kg per day via gavage. Lung injury was evaluated using the ratio of wet-to-dry weight, peripheral bronchial epithelial thickness, degree of angioedema, acute lung injury score, neutrophil infiltration, and cytokine concentrations in bronchoalveolar lavage fluid. RESULTS: Compared with sham treatment, ischemia with no reperfusion (IR 0h) and ischemia with reperfusion for 24 h (IR 24 h) significantly upregulated AQP1 expression, increased the wet/dry weight ratio, angioedema, neutrophil infiltration and cytokine production (interleukin -6 and tumor necrosis factor -α) and thickened the peripheral bronchial epithelium. AZA exacerbated inflammation and pulmonary edema. CONCLUSION: AQP1 may exert a protective effect against IR-induced lung injury, which could be attributed to alleviating pulmonary edema and inflammation. AQP1 upregulation might be a potential application to alleviate lung IRI and decrease the incidence of PGD.

Trans-Polyisoprene/Poly (Ethylene-co-Vinyl Acetate) Polymer Composites as High-Performance Triple Shape Memory Materials.

The performance and programming conditions of the triple shape memory of crosslinked trans-polyisoprene/poly (ethylene-co-vinyl acetate) (TPI/EVA) composites with different contents of dicumyl peroxide (DCP) were investigated. The effect of triple shape memory in the TPI/EVA composites was studied by tensile loading, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and dynamic thermomechanical analysis (DMA). It was demonstrated that the content of DCP increased, the crystallization temperature of TPI decreased from 55.2 to 38.3 °C, and the crystallization temperature of EVA decreased slightly. The SEM results showed that DCP, as an initiator, could form a graft copolymer of TPI-g-EVA at the interface of the two phases, which could improve the adhesion of the two phases. The DMA showed that the higher the content of DCP, the higher the first-stage shape recovery ratio. Moreover, the composites exhibited favorable shape fixity ratio (Rf) and shape recovery ratio (Rr) with the incorporation of 0.4 phr DCP. At the same time, it was demonstrated that the TPI/EVA composites showed excellent mechanical strength, including tensile strength up to 24.3 MPa, as well as elongation at break reaching 508%.

Necrostatin-1 Alleviates Lung Ischemia-Reperfusion Injury via Inhibiting Necroptosis and Apoptosis of Lung Epithelial Cells.

Lung ischemia-reperfusion injury (LIRI) is associated with many diseases, including primary graft dysfunction after lung transplantation, and has no specific and effective therapies. Necroptosis contributes to the pathogenesis of ischemia-reperfusion injury. Necrostatin-1 (Nec-1), the necroptosis inhibitor targeting RIPK1, has been reported to alleviate ischemia-reperfusion injury in various organs. However, the underlying mechanism of Nec-1 in LIRI remains unclear. In this paper, an in vivo LIRI model was built up by left lung hilar clamping in mice, and an in vitro cold ischemia-reperfusion (CI/R) model using BEAS-2B cells was applied to mimic the lung transplantation setting. We found Nec-1 significantly alleviated ischemia-reperfusion-induced lung injury, cytokine releasing, and necroptosis of epithelial cells in mouse lungs. In vitro, Nec-1 also mitigated CI/R-induced cell death and inflammatory responses in BEAS-2B cells, and these protective effects were achieved by simultaneously inhibiting the formation of necrosome and RIPK1-dependent apoptosis. However, Nec-1 decreased the necrosome number but increased the apoptosis level in lung tissues after ischemia reperfusion. We further clarified that Nec-1 could also attenuate lung injury by promoting neutrophil apoptosis from flow cytometry. In conclusion, Nec-1 alleviated lung ischemia-reperfusion injury by inhibiting necroptosis and apoptosis of epithelial cells and promoting the apoptosis of neutrophils. Thus, Nec-1 could be a promising medication against primary graft dysfunction after lung transplantation.

Nav1.8 in keratinocytes contributes to ROS-mediated inflammation in inflammatory skin diseases.

Reactive oxygen species (ROS)-activated proinflammatory signals in keratinocytes play a crucial role in the immunoregulation of inflammatory skin diseases, including rosacea and psoriasis. Nav1.8 is a voltage-gated sodium ion channel, and its abnormal expression in the epidermal layer contributes to pain hypersensitivity in the skin. However, whether and how epidermal Nav1.8 is involved in skin immunoregulation remains unclear. This study was performed to identify the therapeutic role of Nav1.8 in inflammatory skin disorders. We found that Nav1.8 expression was significantly upregulated in the epidermis of rosacea and psoriasis skin lesions. Nav1.8 knockdown ameliorated skin inflammation in LL37-and imiquimod-induced inflammation mouse models. Transcriptome sequencing results indicated that Nav1.8 regulated the expression of pro-inflammatory mediators (IL1ß and IL6) in keratinocytes, thereby contributing to immune infiltration in inflammatory skin disorders. In vitro, tumor necrosis factor alpha (TNFα), a cytokine that drives the development of various inflammatory skin disorders, increased Nav1.8 expression in keratinocytes. Knockdown of Nav1.8 eliminated excess ROS production, thereby attenuating the TNFα-induced production of inflammatory mediators; however, a Nav1.8 blocker did not have the same effect. Mechanistically, Nav1.8 reduced superoxide dismutase 2 (SOD2) activity by directly binding to SOD2 to prevent its deacetylation and mitochondrial localization, subsequently inducing ROS accumulation. Collectively, our study describes a central role for Nav1.8 in regulating pro-inflammatory responses in the skin and indicates a novel therapeutic strategy for rosacea and psoriasis.

Information infrastructure and greenhouse gas emission performance in urban China: A difference-in-differences analysis.

Owing to its network spillover effect, information infrastructure performs outstandingly in promoting economic growth and technological innovation, and has received widespread attention. However, the ecological performance of information infrastructure, especially its impact on greenhouse gas (GHG) emission performance, has been less studied. To investigate this issue, using panel data for 281 prefecture-level cities in China from 2003 to 2018, we treat the Broadband China policy as a quasi-natural experiment in information infrastructure, and conduct a difference-in-differences (DID) analysis. The results show that: (1) Information infrastructure significantly improves urban GHG emission performance. This conclusion holds even after controlling for pilot selection endogeneity, sampling bias, and other policy interference. (2) Technological innovation, industrial structure upgrading, factor allocation enhancement, and tertiary agglomeration are effective channels for information infrastructure to improve GHG emission performance. (3) The treatment effect varies with city size, digital economy level, and economic status. Specifically, information infrastructure exhibits significant emission reduction performance in cities with large size, advanced digital economy, and leading economic status, while the emission reduction effect drops in other cities. This study provides insights into the transition to a carbon-neutral manner for infrastructure in China and other developing countries.

Extracellular Matrix-Based Conductive Interpenetrating Network Hydrogels with Enhanced Neurovascular Regeneration Properties for Diabetic Wounds Repair.

The critical effects that impair diabetic wound healing are characterized by poor vascularization and severe peripheral neuropathy. Current management strategies for diabetic wound healing are unsatisfactory, due to the paucity of neurovascular regeneration at the wound site. Importantly, conductivity in skin tissue is reported to be essential for modulating myriad biological processes especially vascular and nerve regeneration. Herein, an extracellular matrix (ECM)-based conductive dressing is synthesized from an interpenetrating polymer network hydrogel composed of gelatin methacryloyl, oxidized chondroitin sulfate (OCS), and OCS-polypyrrole conductive nanoparticles that can promote diabetic wound repairing by enhancing local neurovascular regeneration. The conductive hydrogels combine the advantageous features of water-swollen hydrogels with conductive polymers (CPs) to provide tissue-matching electrical conductivity and mechanical properties for neurovascular regeneration. In vitro and in vivo studies show that the conductive hydrogel can promote neurovascular regeneration by increasing intracellular Ca2+ concentration, which subsequently promotes phosphorylation of proteins in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways. Furthermore, the conductive hydrogel stimulates full-thickness diabetic wound repair on day 14 by promoting local neurovascular regeneration and collagen deposition. These findings corroborate that the ECM-based conductive interpenetrating network hydrogel dressing significantly promotes wound repairing due to its neurovascular regeneration properties, suggesting that they are suitable candidates for diabetic wound repair.

Bioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea.

Rosacea is significantly associated with dementia, particularly Alzheimer's disease (AD). However, the common underlying molecular mechanism connecting these two diseases remains limited. This study aimed to reveal the common molecular regulatory networks and identify the potential therapeutic drugs for rosacea and AD. There were 747 overlapped DEGs (ol-DEGs) that were detected in AD and rosacea, enriched in inflammation-, metabolism-, and apoptosis-related pathways. Using the TF regulatory network analysis, 37 common TFs and target genes were identified as hub genes. They were used to predict the therapeutic drugs for rosacea and AD using the DGIdb/CMap database. Among the 113 predicted drugs, melatonin (MLT) was co-associated with both RORA and IFN-γ in AD and rosacea. Subsequently, network pharmacology analysis identified 19 pharmacological targets of MLT and demonstrated that MLT could help in treating AD/rosacea partly by modulating inflammatory and vascular signaling pathways. Finally, we verified the therapeutic role and mechanism of MLT on rosacea in vivo and in vitro. We found that MLT treatment significantly improved rosacea-like skin lesion by reducing keratinocyte-mediated inflammatory cytokine secretion and repressing the migration of HUVEC cells. In conclusion, this study contributes to common pathologies shared by rosacea and AD and identified MLT as an effective treatment strategy for rosacea and AD via regulating inflammation and angiogenesis.

Exploring metformin as a candidate drug for rosacea through network pharmacology and experimental validation.

Rosacea is a common chronic inflammatory disease that affects the middle of the face. Due to the unclear pathogenesis, the effective treatment options for rosacea remain limited. In this study, weighted gene co-expression network analyses (WGCNA) identified three rosacea-related hub modules, which were involved in immune-, metabolic- and development- related signaling pathways. Next, the key genes from green and brown modules were submitted to CMap database for drug prediction and metformin was identified as a candidate drug for rosacea. Moreover, network pharmacology analysis identified pharmacological targets of metformin and demonstrated that metformin could help in treating rosacea partly by modulating inflammatory and angiogenesis signaling pathways. Finally, we verified the therapeutic role and mechanism of metformin on rosacea in vivo and vitro. We found that metformin treatment significantly improved rosacea-like skin lesions including immune cells infiltration, cytokines/chemokines expression and angiogenesis. Moreover, metformin suppressed LL37- and TNF-α-induced the ROS production and MAPK-NF-κB signal activation in keratinocytes cells. In conclusion, our findings identified and verified metformin as a novel therapeutic candidate for rosacea, and it alleviates the pathological symptoms, possibly by suppressing inflammatory responses, angiogenesis in rosacea.

Shuangshen granules attenuate lung metastasis by modulating bone marrow differentiation through mTOR signalling inhibition.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Shuangshen granules (SSG) have been used to treat lung cancer patients with Qi deficiency and blood stasis for decades. According to clinical experience, SSG indeed improve the quality of life and prolong the survival time of patients with lung cancer after surgery. Each of the components herbs was proved to be effective in anti-cancer therapy. Both the American ginseng and notoginseng belong to genus Panax of the family Araliaceae. Preclinical and clinical studies demonstrated that ginsenosides of them have anti- or preventive activities to various tumors, including cancers of gastric, breast, liver, lung, ovarian, colon, melanoma and leukemia. PDS, such as ginsenoside Rb1, and PTS, such as ginsenoside Rg1 are the main anticancer compositions. Cordyceps sinensis had also been found effective in inhibiting tumour growth and metastasis, especially on tumour associated immune cells, such as macrophages. However, limited information is available regarding potential mechanisms of SSG. Myeloid-derived suppressor cell (MDSC)-mediated immunosuppression, which is closely associated with poor clinical outcomes in cancer patients, may be the target of SSG, which regulate immune function. AIM OF THE STUDY: The present study aimed to explore whether SSG attenuate the differentiation of bone marrow cells (BMCs) into MDSCs by blocking the mTOR signalling, leading to the suppression of lung metastasis. MATERIALS AND METHODS: First, we observed the differentiation of BMCs into MDSCs in vitro and in vivo. BMCs were cultured alone or co-cultured with Lewis lung carcinoma (LLC) cell supernatant in vitro. The effects of different concentrations of SSG, or LLC cell supernatant as a control, on BMC differentiation were detected by flow cytometry and western blotting. Male C57BL/6J mice were subcutaneously implanted with LLC cells, and SSG were administered by gavage twice daily before and after implantation for 7 or 14 days, respectively. The tumour weight, proportion of MDSCs, presence of CD11b+Ly6C+Ly6G- and CD11b+Ly6C+Ly6G+ cells in the bone marrow, blood, and lungs, as well as the expression levels of differentiation-related proteins in the bone marrow and lungs were evaluated. RESULTS: SSG attenuated the differentiation of BMCs into MDSCs, and reduced the fraction of CD11b+Ly6C+Ly6G+ cells by inhibiting the mTOR/S6K1/Myc signalling pathway. In vivo, SSG attenuated differentiation-associated protein markers and reduced the fractions of MDSCs and CD11b+Ly6C+Ly6G+ cells in the bone marrow, blood, and lungs. In addition, SSG administration reduced the tumour weight and inhibited lung metastasis. CONCLUSIONS: SSG may reduce lung metastasis by attenuating BMC differentiation into CD11b+Ly6C+Ly6G+ cells by inhibiting mTOR signalling in vitro and in vivo.

Wireless Electrochemotherapy by Selenium-Doped Piezoelectric Biomaterials to Enhance Cancer Cell Apoptosis.

Cancer residues around the surgical site remain a significant cause of treatment failure with cancer recurrence. To prevent cancer recurrence and simultaneously repair surgery-caused defects, it is urgent to develop implantable biomaterials with anticancer ability and good biological activity. In this work, a functionalized implant is successfully fabricated by doping the effective anticancer element selenium (Se) into the potassium-sodium niobate piezoceramic, which realizes the wireless combination of electrotherapy and chemotherapy. Herein, we demonstrate that the Se-doped piezoelectric implant can cause mitochondrial damage by increasing intracellular reactive oxygen species levels and then trigger the caspase-3 pathway to significantly promote apoptosis of osteosarcoma cells in vitro. Meanwhile, its good biocompatibility has been verified. These results are of great importance for future deployment of wireless electro- and chemostimulation to modulate biological process around the defective tissue.

Ultrafast and On-Demand Oil/Water Separation Membrane System Based on Conducting Polymer Nanotip Arrays.

Ultrafast oil/water separation based on tunable superwettability switch remains a big challenge. Here, inspired by the ultrafast water transport mechanism in sarracenia, we develop a micro/nanostructured porous membrane with conducting polymer nanotip arrays through the surface-initiated polymerizations. By modulating the height (ranging from 49-529 nm) and redox states of nanotips, a smart reversible superwettability switch is facile to obtain with contact angles of water/oil arranging from 161° to about 0°. Besides, liquid transport speed was accelerated more than 1.5 times by increasing the nanotip length. The water flux could reach up to 50326 L m-2 h-1 (1000 times that of a typical industrial ultrafiltration membrane). This is attributed to the stable and continuous water film along the nanotips, which provide a lubrication layer, leading to an increase of permeability. This work provides significant insights into macro/nanostructured membrane design for smart separation, blood lipid filtration, and smart nanoreactors with high permeability.

Artemisinin, a potential option to inhibit inflammation and angiogenesis in rosacea.

BACKGROUND: Rosacea is a facial chronic inflammatory skin disease with dysfunction of immune and vascular system. Artemisinin (ART), an anti-malaria drug, was reported to have several effects including anti-inflammation and anti-angiogenesis activities. However, the role of ART on rosacea remains unclear. OBJECTIVES: To investigate the effects and molecular mechanism of ART on rosacea. METHOD: In rosacea-like mouse model, the phenotype of rosacea lesions was evaluated by redness score, the inflammatory biomarkers were analyzed by qPCR, and the infiltration of inflammatory cells were assessed by IHC analysis and immunofluorescence. In vitro, LL37-induced expression of inflammatory factors in HaCaT cells was detected by qPCR, potential signaling pathways were detected by Western blotting or immunofluorescence. Migration ability of human umbilical vein endothelial cells (HUVECs) was evaluated by cell scratch and transwell assays. RESULT: The skin erythema and histopathological alteration, as well as the elevated pro-inflammatory factors (IL-1ß, IL6, TNFα) and TLR2 were significantly ameliorated by ART treatment in LL37-induced rosacea-like mice. In addition, ART reduced the infiltration of CD4+ T cells, macrophages and neutrophils, and repressed the expression of immune cells related chemokines (CXCL10, CCL20, CCL2 and CXCL2) in mouse lesions. In HaCaT cells, ART significantly decreased the LL37-induced expression of inflammatory biomarkers. Moreover, we found that ART inhibited rosacea-like inflammation via NF-kB signaling pathways in HaCaT cells. Finally, for vascular dysregulation, ART repressed the angiogenesis in mouse model and inhibited the LL37-induced HUVECs migration in vitro. CONCLUSION: ART ameliorated rosacea-like dermatitis by regulating immune response and angiogenesis, indicating that it could represent an effective therapeutic option for patients with rosacea.

Artificially designed hepatitis B virus core particles composed of multiple epitopes of type A and O foot-and-mouth disease virus as a bivalent vaccine candidate.

Recently, many countries, including China, have experienced a series of type A and O foot-and-mouth disease virus (FMDV) epidemics, causing serious economic losses. Although concerns about the safety of inactivated FMD vaccines have been raised, the development of a safe and effective subunit vaccine is necessary. We constructed two chimeric virus-like particles (VLPs; rHBc/AO and rHBc/AOT VLPs) displaying tandem repeats of B cell epitopes (VP1 residue 134-161 and 200-213) derived from type A and O FMDV and one T cell epitope (3 A residue 21-35) using the truncated hepatitis B virus core (HBc) carrier. Our results indicate that the chimeric HBc can self-assemble into VLPs with these FMDV epitopes displayed on the surface. Immunization with the chimeric VLPs induced specific IgG and neutralization antibodies against type A and O FMDV in mice. Compared with the commercial type A/O FMDV bivalent inactivated vaccine, rHBc/AO and rHBc/AOT VLPs significantly stimulated the production of Th1 type cytokines (IFN-γ and IL-2), whereas Th2 cytokine production (IL-4 and IL-10) was decreased. Compared with rHBc/AO, rHBc/AOT induced increased Th2 cytokine and specific IgG production. These results demonstrate that the VLPs constructed in the current study induced both humoral and cellular immune responses and may represent potential bivalent VLP vaccines targeting both FMDV type A and O strains.

Circulating Iron Levels Interaction with Central Obesity on the Risk of Nonalcoholic Fatty Liver Disease: A Case-Control Study in Southeast China.

OBJECTIVES: We aimed to evaluate the associations between body iron stores and the risk of nonalcoholic fatty liver disease (NAFLD) in a Chinese population and explore whether this effect may be modified by other factors. METHODS: A 1: 1 frequency-matched case-control study was conducted, including 482 NAFLD cases and 490 gender- and age-matched controls. Serum levels of ferritin, hepcidin, and C-reactive protein were measured. RESULTS: Multivariate logistic regression analysis showed that hepcidin was not associated with NAFLD risk; however, elevated serum ferritin was significantly associated with increased risk of NAFLD (adjusted OR 1.619, 95% CI 1.158-2.267), and hepcidin:ferritin ratio was significantly associated with decreased risk of NAFLD -(OR-adjusted 0.702, 95% CI 0.501-0.984). When stratified by gender, a significant association was found between elevated serum ferritin and hepcidin:ferritin ratio and NAFLD only for women (ORadjusted 2.131, 95% CI 1.151-3.944 and ORadjusted 0.414, 95% CI 0.219-0.781, respectively). A significant multiplicative interaction between central obesity and elevated serum hepcidin was observed (p < 0.05). CONCLUSIONS: Elevated serum ferritin and hepcidin:ferritin ratio are associated with NAFLD in a Chinese population. Although serum hepcidin is not associated with NAFLD, it may augment the risk effect of central obesity on NAFLD.

The antibacterial effect of potassium-sodium niobate ceramics based on controlling piezoelectric properties.

The implant infection is one of the most serious postsurgical complications of medical device implantation. Therefore, the development of biocompatible materials with improved antibacterial properties is of great importance. It might be a new insight to apply the intrinsic electrical properties of biomaterials to solve this problem. Here, potassium-sodium niobate piezoceramics (K0.5Na0.5NbO3, KNN) with different piezoelectric constants were prepared, and the microstructures and piezoelectric properties of these piezoceramics were evaluated. Moreover, the antibacterial effect and biocompatibility of these piezoceramics were assayed. Results showed that these piezoceramics were able to decrease the colonies of bacteria staphylococcus aureus (S. aureus), favor the rat bone marrow mesenchymal stem cells (rBMSCs) proliferation and promote the cell adhesion and spreading. The above effects were found closely related to the surface positive charges of the piezoceramics, and the sample bearing the most positive charges on its surface (sample 80KNN) had the best performance in both antibacterial effect and biocompatibility. Based on our work, it is feasible to develop biocompatible antibacterial materials by controlling piezoelectric properties.

Tranexamic acid ameliorates rosacea symptoms through regulating immune response and angiogenesis.

Rosacea is a chronic inflammatory cutaneous disease characterized by immune system anomalies and vascular hyperreactivity. Recently, therapy of rosacea has improved substantially with the approval of Tranexamic acid (TXA), an antifibrinolytic agent. However, we know little about the underlying mechanism. In this study, we evaluated the effects of TXA and its molecular mechanism on rosacea by using LL37-induced mouse model and HaCaT cell model. Rosacea-like symptoms including skin erythema and histopathological alterations, as well as the elevated pro-inflammatory cytokines (IL-6 and TNFα) and MMP9 expression were significantly ameliorated by TXA treatment. In addition, TXA reduced the expression levels of innate immune gene (TLR2, KLK5 and Camp) and neutrophils relative gene in rosacea-like lesion. For adaptive immune, CD4+ T cell infiltration and the gene expression of Th cytokines and chemokines were regulated by TXA in skin lesion. Furthermore, the anti-inflammatory effects of TXA were associated with the inhibition of TLR2, pro-inflammatory cytokines (IL-6 and TNFα) and chemokines (CCL10) expression in LL37-activated HaCaT cells. Finally, TXA repressed the angiogenesis by reducing the number of CD31+ cell and downregulating the expression levels of VEGF in rosacea. In conclusion, our finding defines a treatment mechanism by which TXA ameliorates rosacea symptoms by regulating the immune response and angiogenesis.