Kinetic Modulation of Carbon Nanotube Growth in Direct Spinning for High-Strength Carbon Nanotube Fibers.

With impressive individual properties, carbon nanotubes (CNTs) show great potential in constructing high-performance fibers. However, the tensile strength of as-prepared carbon nanotube fibers (CNTFs) by floating catalyst chemical vapor deposition (FCCVD) is plagued by the weak intertube interaction between the essential CNTs. Here, we developed a chlorine (Cl)/water (H2O)-assisted length furtherance FCCVD (CALF-FCCVD) method to modulate the intertube interaction of CNTs and enhance the mechanical strength of macroscopic fibers. The CNTs acquired by the CALF-FCCVD method show an improvement of 731% in length compared to that by the conventional iron-based FCCVD system. Moreover, CNTFs prepared by CALF-FCCVD spinning exhibit a high tensile strength of 5.27 ± 0.27 GPa (4.62 ± 0.24 N/tex) and reach up to 5.61 GPa (4.92 N/tex), which outperforms most previously reported results. Experimental measurements and density functional theory calculations show that Cl and H2O play a crucial role in the furtherance of CNT growth. Cl released from the decomposition of methylene dichloride greatly accelerates the growth of the CNTs; H2O can remove amorphous carbon on the floating catalysts to extend their lifetime, which further modulates the growth kinetics and improves the purity of the as-prepared fibers. Our design of the CALF-FCCVD platform offers a powerful way to tune CNT growth kinetics in direct spinning toward high-strength CNTFs.

Monocyte distribution width as an early predictor of short-term outcome in adult patients with sepsis.

OBJECTIVES: Monocyte distribution width (MDW) is a quantitative measurement of monocyte anisocytosis and has been proposed as an efficient marker for early sepsis detection. This study aimed to assess the prognostic potential of MDW in septic patients. METHODS: In this study, a total of 252 adult septic patients were enrolled. Demographic, clinical, and laboratory finding including MDW and traditional inflammatory biomarkers detected at three time points (day 1, day 3 and day 6) after admission were collected and compared between 28-day survivors and non-survivors. Receiver operating characteristic (ROC) curves, Kaplan-Meier survival curve and Cox regression analyses were performed to assess and compare their predictive values. Group-based trajectory modeling was applied to identify MDW trajectory endotypes. Basic characteristics and 28-day outcomes were compared between the trajectories. RESULTS: ROC curve analysis showed that MDW levels measured on day 3 after admission (D3-MDW) had moderate prognostic value and was independently associated with 28-day mortality in patients with sepsis. A D3-MDW value of 26.20 allowed discrimination between survivors and non-survivors with a sensitivity of 77.8 % and a specificity of 67.6 %. However, the prognostic accuracy of D3-MDW was diminished in immune-compromised patients and patients who already received antibiotics before admission. Group-based trajectory modeling indicated that excessively elevated and delayed decreased MDW levels during the first week after admission inversely correlated with prognosis. CONCLUSIONS: MDW values detected on day 3 after admission and its kinetic change might be potential markers for predicting short-term outcome in adult septic patients.

AQP8 promotes glioma proliferation and growth, possibly through the ROS/PTEN/AKT signaling pathway.

BACKGROUND: The aquaporin (AQP) family of proteins has been implicated in the proliferation and growth of gliomas. Expression of AQP8 is higher in human glioma tissues than in normal brain tissues and is positively correlated with the pathological grade of glioma, suggesting that this protein is also involved in the proliferation and growth of glioma. However, the mechanism by which AQP8 promotes the proliferation and growth of glioma remains unclear. This study aimed to investigate the mechanism and role of abnormal AQP8 expression in glioma development. METHODS: The dCas9-SAM and CRISPR/Cas9 techniques were used to construct viruses with overexpressed and knocked down AQP8, respectively, and infect A172 and U251 cell lines. The effects of AQP8 on the proliferation and growth of glioma and its mechanism via the intracellular reactive oxygen species (ROS) level were observed using cell clone, transwell, flow cytometry, Hoechst, western blotting, immunofluorescence, and real-time quantitative polymerase chain reaction assays. A nude mouse tumor model was also established. RESULTS: Overexpression of AQP8 resulted in an increased number of cell clones and cell proliferation, enhanced cell invasion and migration, decreased apoptosis and phosphatase and tensin homolog (PTEN) expression, and increased phosphorylated serine/threonine protein kinase (p-AKT) expression and ROS level, whereas the AQP8 knockdown groups showed opposite results. In the animal experiments, the AQP8 overexpression group had higher tumor volume and weight, whereas the AQP8 knockdown group had lower tumor volume and weight compared with those parameters measured in the control group. CONCLUSIONS: Our results preliminary suggest that AQP8 overexpression alters the ROS/PTEN/AKT signaling pathway, promoting the proliferation, migration, and invasion of gliomas. Therefore, AQP8 may be a potential therapeutic target in gliomas.

Carbonene Fibers: Toward Next-Generation Fiber Materials.

The development of human society has set unprecedented demands for advanced fiber materials, such as lightweight and high-performance fibers for reinforcement of composite materials in frontier fields and functional and intelligent fibers in wearable electronics. Carbonene materials composed of sp2-hybridized carbon atoms have been demonstrated to be ideal building blocks for advanced fiber materials, which are referred to as carbonene fibers. Carbonene fibers that generally include pristine carbonene fibers, composite carbonene fibers, and carbonene-modified fibers hold great promise in transferring the extraordinary properties of nanoscale carbonene materials to macroscopic applications. Herein, we give a comprehensive discussion on the conception, classification, and design strategies of carbonene fibers and then summarize recent progress regarding the preparations and applications of carbonene fibers. Finally, we provide insights into developing lightweight, high-performance, functional, and intelligent carbonene fibers for next-generation fiber materials in the near future.

(n, m) Distribution of Single-Walled Carbon Nanotubes Grown from a Non-Magnetic Palladium Catalyst.

Non-magnetic metal nanoparticles have been previously applied for the growth of single-walled carbon nanotubes (SWNTs). However, the activation mechanisms of non-magnetic metal catalysts and chirality distribution of synthesized SWNTs remain unclear. In this work, the activation mechanisms of non-magnetic metal palladium (Pd) particles supported by the magnesia carrier and thermodynamic stabilities of nucleated SWNTs with different (n, m) are evaluated by theoretical simulations. The electronic metal-support interaction between Pd and magnesia upshifts the d-band center of Pd, which promotes the chemisorption and dissociation of carbon precursor molecules on the Pd surface, making the activation of magnesia-supported non-magnetic Pd catalysts for SWNT growth possible. To verify the theoretical results, a porous magnesia supported Pd catalyst is developed for the bulk synthesis of SWNTs by chemical vapor deposition. The chirality distribution of Pd-grown SWNTs is understood by operating both Pd-SWNT interfacial formation energy and SWNT growth kinetics. This work not only helps to gain new insights into the activation of catalysts for growing SWNTs, but also extends the use of non-magnetic metal catalysts for bulk synthesis of SWNTs.

Effects of a brief afternoon nap on declarative and procedural memory.

The relationship between sleep and memory consolidation has not been fully revealed. The current study aimed to investigate how a brief afternoon nap contributed to the consolidation of declarative and procedural memory by exploring the relationship between sleep characteristics (i.e., the durations of sleep stages and slow oscillation, slow-wave activity, and spindle activity extracted from sleep) and task performance and the relationship between delta, theta, alpha, and beta bands extracted from wake during task performance and task performance. Twenty-three healthy young adults underwent a paired associates learning task and a sequential finger-tapping task with easy and difficult levels and were tested for memory performance before and after the intervention (i.e., an about 30-min nap or stay awake). Electroencephalogram (EEG) signals were continously recorded during the whole experiment. Results revealed that a short afternoon nap improved movement speed for the procedural memory task, regardless of the task difficulty, but unaffected the performance on the declarative memory task. Besides, the improvement in movement speed for the easy procedural memory task was positively correlated with slow-wave activity (SWA) during non-rapid-eye-movement (NREM) sleep but negatively correlated with slow oscillation and spindle activity during sleep stage 2 and NREM sleep, and the improvement in the difficult procedural memory task correlated positively with SWA during NREM sleep. Moreover, performance on the easy declarative and procedural memory tasks was negatively correlated with the relative power of alpha or theta; whereas the alpha band was positively correlated with the difficult declarative memory performance. These findings suggested that a brief afternoon nap with NREM sleep would benefit procedural memory consolidation but not declarative memory; such contribution of napping to memory consolidation would be either explained by the sleep characteristics or physiological arousal during performing tasks; task difficulty would moderate the relationship between the declarative memory performance and EEGs during task performance.

Building a Bridge for Carbon Nanotubes from Nanoscale Structure to Macroscopic Application.

Through 30 years of research, researchers have gained a deep understanding of the synthesis, characteristics, and applications of carbon nanotubes (CNTs). However, up to now, there are still few industries using CNT as the leading material. The difficulty of CNTs to be applied in industry is the gap between the properties of CNT-based aggregates and those of a single carbon nanotube. Therefore, how to maintain the intrinsic properties of CNTs when they are assembled into aggregates is of great significance. Herein, we summarize and analyze the research status of CNT materials applied in different fields from proven techniques to potential industries, including energy storage, electronics, mechanical and other applications. For each application, the intrinsic properties of CNTs and the real performances of their aggregates are compared to figure out the key problems in CNT synthesis. Finally, we give an outlook for building a bridge for CNTs from nanoscale structure to macroscopic application, giving inspiration to researchers making efforts toward the real application of carbon nanotubes.

Effects of bright light and an afternoon nap on task performance depend on the cognitive domain.

Previous research revealed inconsistent effects of bright light or a short nap at noon on alertness and performance across different tasks. The current study aimed to explore whether the effects of bright light and a short nap at noon on task performance depended on the cognitive domain. Bright light (1,200 lx, 4,000 K at eye level), nap (near darkness) and control (200 lx, 4,000 K at eye level) conditions were performed from 1:00 to 1:40 PM on three non-consecutive days with a counterbalanced order across participants. After being assigned to one of three conditions, participants underwent two repeated test sessions, each including a psychomotor vigilance task, a go/no-go task, and a paced visual serial addition task, with an interval of more than 1 h, to assess the persistent effects of napping and bright light. Subjective sleepiness, vitality, self-control and mood were also measured. Results showed that accuracy on the go/no-go task and the paced visual serial addition task improved significantly throughout the entire experiment session after napping, whereas reaction speed on the paced visual serial addition task improved time-dependently in the bright light intervention, with a higher reaction speed in only the first test session. Nearly all subjective states benefited from napping but not from bright light. These findings suggested that the effects of bright light and an afternoon nap on task performance would depend on the cognitive domain. An afternoon nap may elicit more effective and persistent benefits on task performance and subjective states.

Anxiety and depression are risk factors for recurrent pregnancy loss: a nested case-control study.

BACKGROUND: To evaluate the interaction of depression and anxiety with the development of recurrent pregnancy loss (RPL). METHODS: A nested case-control study involving 2558 participants was conducted with data from the prospective Miscarriage Woman Cohort study between 2017 and 2019 in the province of Gansu, China. The questionnaire data, self-rating anxiety scale and self-rating depression scale were collected after each participant's first miscarriage. Information on RPL outcomes was obtained from the medical records within the subsequent 2 years. All patients diagosed RPL were recruited as cases whilst a randomly selected group of women with only one miscarriage in the past were recruited as controls. The logistic regression and the interaction effects between anxiety and depression and RPL were analysed. RESULTS: The prevalence of anxiety (n = 325, 28.7% vs. n = 278, 19.5%) and depression symptoms (n = 550, 48.6% vs. n = 589, 41.3%) for the 1132 RPL cases were higher than 1426 non-RPL controls (P < 0.001). After adjusting for possible confounding variables, the odds ratio (OR) value, reflecting the multiplicative interaction, was 1.91 (95% CI 1.50-2.44, P < 0.001) for cases with both anxiety and depression symptoms compared with the non-RPL group. The relative excess risk of interaction value, reflecting the additive interaction between anxiety and depression to RPL was 1.15 (95% CI 0.32-4.21). Moreover, the adjusted OR for RPL cases with mild anxiety and severe depression was 2.77 (95% CI 1.07-44.14, P < 0.001), for RPL cases with severe anxiety and mild depression was 4.23 (95% CI 1.01-22.21, P < 0.001), for RPL cases with severe anxiety and moderate depression was 4.34 (95% CI 1.03-21.28, P < 0.001) and for RPL cases with severe anxiety and severe depression was 5.95 (95% CI 1.09-45.09, P < 0.05). CONCLUSIONS: Either depression or anxiety alone could increase the risk of subsequent RPL. Anxiety and depression had a synergistic effect after the first miscarriage which increased the development of subsequent RPL disease.

Growth of Homogeneous High-Density Horizontal SWNT Arrays on Sapphire through a Magnesium-Assisted Catalyst Anchoring Strategy.

In-situ growth of high-density single-walled carbon nanotube (SWNT) arrays with homogeneity is highly desirable for integrated circuits. However, disastrous migration and aggregation of catalyst nanoparticles on substrate has greatly limited the area of as-grown SWNT arrays. Herein, we develop a magnesium-assisted catalyst anchoring strategy to restrain catalyst nanoparticles sintering on substrate. Magnesium modification ameliorates sapphire surface by high temperature solid reaction and thus provides a stronger metal-support interaction (SMSI). Hereby, we realize the direct growth of high-density SWNT arrays that fully cover an entire 10×10 mm2 substrate with the local highest density of ≈110 tubes µm-1 using iron as catalyst. This strategy was also proven universal when employing solid carbide catalysts.

[Active components and mechanism of Taohong Siwu Decoction in treatment of primary dysmenorrhea based on network pharmacology and molecular docking technology].

This paper aimed to investigate the active components and mechanism of Taohong Siwu Decoction in the treatment of primary dysmenorrhea(PD) based on network pharmacology and molecular docking technology. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was used to search the chemical compositions and targets of six herbs in Taohong Siwu Decoction. The targets for PD treatment were selected through the databases of DrugBank, OMIM, TTD and CTD, and gene annotation of the targets was conducted with UniProt database. Cytoscape 3.7.2 was then used to construct the drug-compound-target network. The protein-protein interaction(PPI) network was constructed based on STRING, and the core targets of Taohong Siwu Decoction in the treatment of PD were selected according to the topological parameters. David database was used for GO enrichment analysis and KOBAS 3.0 was used for KEGG enrichment analysis. The molecular docking technology was used to connect the components with higher medium values in the network with core targets. The results showed that the network contained 36 compounds such as quercetin, kaempferol, luteolin, myricanone and ferulic acid, and 99 targets such as PTGS2, PTGS2, PGR and PPARG. Totally 102 GO terms were obtained by GO functional enrichment analysis(P<0.01), and 228 signal pathways were obtained by KEGG pathway enrichment(P<0.05), mainly involving inflammatory factors, hormone regulation, central analgesia, amino acid metabolism and spasmolysis. The results of molecular docking showed that the main active components can spontaneously bind to the targets. This study preliminarily revealed the mechanism of Taohong Siwu Decoction for treatment of primary dysmenorrheal through multi-components, multi-targets and multi-pathways, providing theoretical references for further researches on mechanism of Taohong Siwu Decoction.

[Recommendations on quality standards of Andrographis Herba and its processed slices in Chinese Pharmacopoeia (2020 edition)].

To improve and perfect the quality standards and propose recommendations for the revision of quality standards for Andrographis Herba and its processed slices in Chinese Pharmacopoeia(ChP)(2020 edition) based on the problems and limitations in ChP(2015 edition). TLC identification method with andrographolide and control herbs as references was established using silica gel G thin layer plate, with chloroform-methylbenzene-methanol(8∶1∶1) as developing solvent, and 10% sulfuric acid ethanol solution as colour-developing agent. This method has good reproducibility, strong specificity and high sensitivity. As compared with the original method in ChP 2015, this method has better development effect and clearer spots. Based on the previous research, a quantitative analysis of multi-components by single-marker(QAMS) method with andrographolide as the internal reference substance was developed to simultaneously determine the contents of 4 diterpene lactones: andrographolide(S), neoandrographolide(A), 14-deoxyandrographolide(B), and dehydroandrographolide(C). The relative correction factors of f_(A/S), f_(B/S), and f_(C/S) were determined as 1.12, 0.79, and 0.63, respectively. The relative retention time of t_(A/S), t_(B/S), and t_(C/S) was 1.95, 2.18, and 2.25, respectively. According to the content determination results in 46 batches of crude drugs and 38 batches of processed slices, it was stipulated that the total contents of 4 diterpene lactones should not be less than 1.5% and 1.2% in crude drugs and processed slices, respectively. As compared with the original method in ChP 2015, the present QAMS method could not only reduce the detection cost and improve the efficiency, but also can be used to evaluate the quality of Andrographis Herba and its processed slices more comprehensively and objectively. Diterpene lactones are generally recognized as the effective components in Andrographis Herba, and their contents in leaves were much higher than those in stems. However, almost all of the current commercial processed slices are processed from stems, so their quality is gene-rally poor and the efficacy is hard to be guaranteed. Therefore, the weight percentage of leaves should be added into the inspection items of the processed slices and it should not be less than 25%.

Growth of Single-Walled Carbon Nanotubes with Controlled Structure: Floating Carbide Solid Catalysts.

Single-walled carbon nanotube (SWNT) horizontal arrays with specific chirality can be enriched using solid carbide catalysts on substrates. However, scale-up production by continuous loading of the solid catalysts onto the substrates is challenging. Described here is the preparation of a floating carbide solid catalyst (FSC) for the controlled growth of SWNTs. The FSC, titanium carbide (TiC) nanoparticle, was directly obtained in the carrier gas phase by decomposition and carbonization of the titanocene dichloride precursor at high temperature. By using the TiC nanoparticle FSC, both SWNT horizontal arrays and randomly distributed networks can be obtained. The chirality of the as-grown SWNTs were thermodynamically controlled to have fourfold symmetry. Further optimization of growth condition resulted in an abundance of (16,8) tubes with about a 74 % content. This FSC chemical vapor deposition (FSCCVD) method has potential for realizing mass growth of SWNTs with controlled structures.

Evaluation of the implementation and effect of the healthcare cloud information platform for diabetes self-management: A case study in Shanghai.

With the high prevalence of diabetes, its long-term treatment, and many complications, there is a need for a new diabetes self-management model in developing countries. Therefore, this study aimed to assess the implementation and effect of a new diabetes self-management model, known as the healthcare cloud information platform, in Shanghai, China. The implementation of the new model was evaluated in terms of the equipment coverage in community health service centres and the services provided. The effect was assessed according to the treatment rate and control rate from 2012 to 2017. Their correlations with the self-management rate were analysed using Spearman's test. It was found that the Shanghai healthcare cloud information platform had covered a total of 237 community health service centres in all of the 16 administrative districts, equipping them with 2489 health stations, by 2017. An average of 8966 people uploaded data to the healthcare cloud information platform every day, with the accumulated service up to 12 043 508 person-times and an average daily increase of 13 227.9. The treatment rate of diabetes patients in Shanghai increased from 42.9% in 2012 to 78.0% in 2017, and the control rate increased to 72% in 2017, compared with 63% in 2012. Furthermore, there was a significant correlation between the treatment rate, control rate, and self-management rate. The findings indicate that it is feasible to implement the new healthcare cloud information platform for diabetes self-management and that it is effective.

Toothache as a Warning Sign of Subarachnoid Hemorrhage Postmortem Findings.

The symptoms of sudden severe headache and/or diminished consciousness characterize the onset of aneurysmal subarachnoid hemorrhage (SAH). However, several studies have suggested that some patients show an atypical presentation at the onset: symptoms lacking sudden headache and diminished consciousness. These atypical symptoms can easily lead to misdiagnosis. This paper reported the death cases of acute aneurysmal subarachnoid hemorrhage with toothache as the first symptom, hoping to provide clinical evidence for the general public doctors to reduce the misdiagnosis and delayed diagnosis of SAH, improve the identification ability of SAH, and prevent such death events from happening again.

[Preventive effect and mechanism of ultrafine powder of Dendrobium candidum on photoaging model mice].

Chinese herbal medicine ultrafine powder has become a research hotspot for the addition of cosmetic raw materials. Dendrobium candidum is a traditional Chinese herbal medicine. Its extract and stem extract are already cosmetic raw materials and its water extract has the effect of preventing photoaging,but D. candidum ultrafine powder has not been accepted as a raw material for cosmetics,and no relevant research on photoaging prevention has been reported. In this experiment,the ultra-fine powder and fine powder of D. candidum to prevent photoaging were observed and compared,and its mechanism of action was discussed to provide a basis for the prevention of skin photoaging products. Seventy-two female ICR mice were randomly divided into normal group,model group,solvent group,titanium dioxide(Ti O2) group,isooctyl salicylate(2-ES) group,D. candidum ultrafine powder 1(DP1),ultrafine powder 2(DP2) and fine powder(DP3) groups. The photoaging model was established by ultraviolet irradiation for 8 weeks,and the model was intervened while modeling. The skin wrinkle grade,elastic parameters,skin microcirculation blood flow,skin structure and pathological changes(skin thickness,skin collagen fiber,elastic fiber) were observed,the skin transforming growth factor-ß1(TGF-ß1),Smad3 levels were determined,and the type Ⅰ and type Ⅲ collagen,matrix metalloproteinase-1(MMP-1),activated protein-1(AP-1),VEGF expression were detected. The results showed that ultrafine powder(DP1,DP2) significantly reduced the wrinkle level and skin blood flow of the model mice(P<0. 05,P<0. 01); DP1,DP2 and DP3 could significantly reduce the thickness of the epidermis(P<0. 001),improve collagen fiber,elastic fiber hyperplasia,and distortion and decrease VEGF expression,and DP1 is better than DP2 and DP3; each group could up-regulate type Ⅰ collagen,down-regulate type Ⅲ collagen,AP-1,MMP-1 protein expression,and DP1 improvement optimal. However,it has no obvious effect on TGF-ß1 and Smad3. The ultrafine powder and fine powder of D. candidum have certain preventive effect on photoaging,and the effect of ultrafine powder is better than that of fine powder. Ultrafine powder may down-regulate the expression of type Ⅲ collagen,AP-1 and MMP-1 by up-regulating type Ⅰ collagen. Inhibition of collagen degradation plays a role in preventing photoaging.

Detection of circulating tumor cells in patients with pituitary tumors.

BACKGROUND: Circulating tumor cells (CTCs) are tumor cells that have shed from a primary tumor and circulate in the peripheral blood. Recent experimental and clinical studies show that CTCs can be detected in early-stage disease. CASE PRESENTATION: We report three cases of pituitary adenoma (PA) in which tumor cells with particles were detected in the interstitial vascular compartment by transmission electron microscopy. Tumors were completely resected. Immunohistochemical analysis showed a ß-catenin score of 10.5 ± 1.5 in the three cases with CTCs compared with 2.4 ± 0.5 in 24 control adenomas. The Ki-67 labeling index was 2.1 ± 0.7 in CTCs vs. 0.2 ± 0.3 in control cases (p = 0.043), and the p53 score was 4.33 ± 1.3 vs. 0.31 ± 0.17 (p = 0.000). The E-cadherin score did not differ significantly between the two groups. CONCLUSIONS: CTCs can be detected in benign tumors such as PAs and not only in late-stage malignant tumors with apparent distant metastases. The present findings suggest that pituitary carcinomas develop from adenomas.

High-performance gas sensors based on a thiocyanate ion-doped organometal halide perovskite.

Thin films of a thiocyanate ion (SCN-)-doped organometal halide perovskite, CH3NH3PbI3-x(SCN)x, were used as a sensing material for developing high-performance gas sensors. The CH3NH3PbI3-x(SCN)x-based chemiresistor-type sensor can sensitively and selectively detect acetone and nitrogen dioxide (NO2) at room temperature with high sensitivities of 5.6 × 10-3 and 5.3 × 10-1 ppm-1. The limits of detection for acetone and NO2 were measured to be 20 ppm and 200 ppb. This sensor also exhibited excellent repeatability, and its environmental stability was greatly improved by doping the perovskite with SCN- ions.

Adenylyl cyclase 6 activation negatively regulates TLR4 signaling through lipid raft-mediated endocytosis.

Proper intracellular localization of TLRs is essential for their signaling and biological function. Endocytosis constitutes a key step in protein turnover, as well as maintenance of TLR localization in plasma membrane and intracellular compartments, and thus provides important regulating points to their signaling. In this study, we demonstrate that adenylyl cyclase (AC) activation attenuates TLR4 signaling in a murine macrophage cell line (RAW 264.7) and bone marrow-derived macrophages when stimulated with LPS. We further show that the AC6 isoform plays a key role in negative regulation of TLR4 signaling by promoting protein degradation. TLR4 is normally endocytosed through the clathrin-mediated pathway, but concomitant AC6 activation shifts it to lipid raft-mediated endocytosis, which accelerates degradation of TLR4 and suppresses downstream signaling. Our studies unveil a new mechanism of negative regulation of TLR4 signaling through AC6-mediated endocytosis, which might provide a novel therapeutic approach for limiting inflammatory and autoimmune diseases.

Exogenous IFN-beta regulates the RANKL-c-Fos-IFN-beta signaling pathway in the collagen antibody-induced arthritis model.

BACKGROUND: Although a variety of drugs have been used to treat the symptoms of rheumatoid arthritis (RA), none of them are able to cure the disease. Interferon ß (IFN-ß) has pleiotropic effects on RA, but whether it can be used to treat RA remains globally controversial. Thus, in this study we tested the effects of IFN-ß on RA patients and on collagen antibody-induced arthritis (CAIA) model mice. METHODS: The cytokine and auto-antibody expression profiles in the serum and synovial fluid (SF) from RA patients were assessed using enzyme-linked immunosorbent assay (ELISA) and compared with the results from osteoarthritis (OA) patients. Exogenous IFN-ß was administered to RA patients and CAIA model mice, and the therapeutic effects were evaluated. Endogenous IFN-ß expression in the joint bones of CAIA model mice was evaluated by quantitative real-time PCR (qRT-PCR). The effects of exogenous IFN-ß on CAIA model mice were assessed using a clinical scoring system, hematoxylin eosin and safranin-O with fast green counterstain histology, molybdenum target X-ray, and tartrate-resistant acid phosphatase (TRAP) staining. The RANKL-RANK signaling pathway was analyzed using qRT-PCR. The RAW 264.7 cell line was differentiated into osteoclasts with RANKL stimulation and then treated with exogenous IFN-ß. RESULTS: The expression of inflammatory cytokines (IFN-γ, IL-17, MMP-3, and RANKL) and auto-antibodies (CII antibodies, RF-IgM, and anti-CCP/GPI) were significantly higher in RA compared with OA patients. After IFN-ß intervention, some clinical symptoms in RA patients were partially alleviated, and the expression of IFN-γ, IL-17, MMP-3, and OPG) returned to normal levels. In the CAIA model, the expression of endogenous IFN-ß in the joint bones was decreased. After IFN-ß administration, the arthritis scores were decreased; synovial inflammation, cartilage, and bone destruction were clearly attenuated; and the expression of c-Fos and NFATc1 were reduced, while RANKL and TRAF6 expression was unchanged. In addition, exogenous IFN-ß directly inhibited RANKL-induced osteoclastogenesis. CONCLUSIONS: Exogenous IFN-ß administration immunomodulates CAIA, may reduce joint inflammation and, perhaps more importantly, bone destruction by inhibiting the RANKL-c-Fos signaling pathway. Exogenous IFN-ß intervention should be selectively used on RA patients because it may only be useful for RA patients with low endogenous IFN-ß expression.