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Understanding the molecular mechanisms regulating the maintenance and destruction of intervertebral disc may lead to the development of new therapies for intervertebral disc degeneration (IDD). Here we present evidence from miRNA microarray analyses of clinical data sets along with in vitro and in vivo experiments that miR-141 is a key regulator of IDD. Gain- and loss-of-function studies show that miR-141 drives IDD by inducing nucleus pulposus (NP) apoptosis. Furthermore, miR-141 KO in mice attenuated spontaneous and surgically induced IDD. Mechanistically, miR-141 promotes IDD development by targeting and depleting SIRT1, a negative regulator of NF-κB pathway. Therapeutically, upregulation or downregulation of miR-141 by nanoparticle delivery in IDD model aggravated or alleviated experimental IDD, respectively. Our findings reveal a novel mechanism by which miR-141, in part, promotes IDD progression by interacting with SIRT1/NF-κB pathway. Blockade of miR-141 in vivo may serve as a potential therapeutic approach in the treatment of IDD. Intervertebral disk degeneration (IDD) is characterized by changes in the nucleus pulposus (NP) extra cellular matrix that compromise disk structural integrity. In a miRNA screen of human IDD patient NP tissue, the authors identify deregulated miR-141 and show that direct injection of nanoparticle-coupled miR-141 into the NP alleviates IDD in mice.

The gut microbiota is reported to modulate the immune response in hepatocellular carcinoma (HCC). Here, we employ metagenomic and metabolomic studies to characterise gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD) related cirrhosis, with or without HCC, and evaluate its effect on the peripheral immune response in an ex vivo model. We find that dysbiosis characterises the microbiota of patients with NAFLD-cirrhosis, with compositional and functional shifts occurring with HCC development. Gene function of the microbiota in NAFLD-HCC supports short chain fatty acid production, and this is confirmed by metabolomic studies. Ex vivo studies show that bacterial extracts from the NAFLD-HCC microbiota, but not from the control groups, elicit a T cell immunosuppressive phenotype, characterised by expansion of regulatory T cells and attenuation of CD8 + T cells. Our study suggest that the gut microbiota in NAFLD-HCC is characterised by a distinctive microbiome/metabolomic profile, and can modulate the peripheral immune response. Disease-specific gut microbiome signatures have been previously defined for patients with liver cirrhosis or hepatocellular carcinoma (HCC). Here the authors examine the composition of the gut microbiota in cirrhotic patients with non-alcoholic fatty liver disease with or without HCC and evaluate how dysbiosis influences peripheral immune responses.

Arrestins recognize different receptor phosphorylation patterns and convert this information to selective arrestin functions to expand the functional diversity of the G protein-coupled receptor (GPCR) superfamilies. However, the principles governing arrestin-phospho-receptor interactions, as well as the contribution of each single phospho-interaction to selective arrestin structural and functional states, are undefined. Here, we determined the crystal structures of arrestin2 in complex with four different phosphopeptides derived from the vasopressin receptor-2 (V2R) C-tail. A comparison of these four crystal structures with previously solved Arrestin2 structures demonstrated that a single phospho-interaction change results in measurable conformational changes at remote sites in the complex. This conformational bias introduced by specific phosphorylation patterns was further inspected by FRET and 1 H NMR spectrum analysis facilitated via genetic code expansion. Moreover, an interdependent phospho-binding mechanism of phospho-receptor-arrestin interactions between different phospho-interaction sites was unexpectedly revealed. Taken together, our results provide evidence showing that phospho-interaction changes at different arrestin sites can elicit changes in affinity and structural states at remote sites, which correlate with selective arrestin functions. The interaction between a GPCR, such as the vasopressin receptor-2 (V2R), and arrestin depends on the receptors’ phosphorylation pattern. Here authors use FRET and NMR to analyze the phosphorylation patterns of the V2R-arrestin complex and show that phospho-interactions are the key determinants of selective arrestin conformational states and correlated functions.

Upland forests are traditionally thought to be net sinks for atmospheric methane (CH4). In such forests, in situ CH4 fluxes on tree trunks have been neglected relative to soil and canopy fluxes. We measured in situ CH4 fluxes from the trunks of living trees and other surfaces, such as twigs and soils, using a static closed-chamber method, and estimated the CH4 budget in a temperate upland forest in Beijing. We found that the trunks of Populus davidiana emitted large quantities of CH4 during July 2014–July 2015, amounting to mean annual emissions of 85.3 and 103.1 μg m−2 h−1 on a trunk surface area basis on two replicate plots. The emission rates were similar in magnitude to those from tree trunks in wetland forests. The emitted CH4 was derived from the heartwood of trunks. On a plot or ecosystem scale, trunk CH4 emissions were equivalent to c. 30–90% of the amount of CH4 consumed by soils throughout the year, with an annual average of 63%. Our findings suggest that wet heartwoods, regardless of rot or not, occur widely in living trees on various habitats, where CH4 can be produced.

Periodontitis is a widespread disease characterized by inflammation‐induced progressive damage to the tooth‐supporting structures until tooth loss occurs. The regeneration of lost/damaged support tissue in the periodontium, including the alveolar bone, periodontal ligament, and cementum, is an ambitious purpose of periodontal regenerative therapy and might effectively reduce periodontitis‐caused tooth loss. The use of stem cells for periodontal regeneration is a hot field in translational research and an emerging potential treatment for periodontitis. This concise review summarizes the regenerative approaches using either culture‐expanded or host‐mobilized stem cells that are currently being investigated in the laboratory and with preclinical models for periodontal tissue regeneration and highlights the most recent evidence supporting their translational potential toward a widespread use in the clinic for combating highly prevalent periodontal disease. We conclude that in addition to in vitro cell‐biomaterial design and transplantation, the engineering of biomaterial devices to encourage the innate regenerative capabilities of the periodontium warrants further investigation. In comparison to cell‐based therapies, the use of biomaterials is comparatively simple and sufficiently reliable to support high levels of endogenous tissue regeneration. Thus, endogenous regenerative technology is a more economical and effective as well as safer method for the treatment of clinical patients. Stem Cells Translational Medicine 2019;8:392–403 Periodontal regeneration can potentially be achieved via either the in vitro design of cell‐material constructs that may undergo remodeling and revascularization to integrate with the host tissue following transplantation or based on the in vivo manipulation of the cell‐material interplay at the target site to recruit endogenous stem cells to regenerate new tissues.

Psittacosis pneumonia is a community-acquired pneumonia caused by Chlamydia psittaci. It is usually under-diagnosed due to its atypical clinical presentation and lack of routine laboratory tests. To better understand the clinical features, 52 patients diagnosed with psittacosis pneumonia by metagenomic next-generation sequencing (mNGS) were enrolled in this study. The clinical, radiological and pathological characteristics were retrospectively analyzed. The onset of psittacosis pneumonia in this study occurred all year round, with a peak from December to January. Most of the patients were 51-80 years old. About 65.38% of patients had a history of exposure to poultry or parrots. Abnormalities of multiple clinical signals were detected in these patients. Elevated levels of neutrophil ratio, C-reactive protein, erythrocyte sedimentation rate, and procalcitonin were detected in most patients. Radiological evidence revealed air-space consolidation or ground-glass opacities in lungs of all patients, which is the typical feature of psittacosis pneumonia. In addition, hyperemia, swelling of bronchial mucosa, and bronchial patency were detected by bronchoscopy in all patients, and bronchial sub-mucosal edema, inflammatory cells infiltration and alveolar epithelial hyperplasia were identified in the bronchial mucosa and alveolar tissue. Beta-lactam antibiotics were administered for empirical treatment before mNGS in 17 patients but showed no improvement. The treatment was switched to doxycycline or moxifloxacin immediately since psittacosis pneumonia were suspected and confirmed by mNGS detection (within 48 hours). After receiving adjustment of treatment, 94.23% (49/52) of patients were cured successfully. In conclusion, mNGS may be a promising approach for clinical diagnosis of psittacosis. For patients with a history of exposure to birds, hyperpyrexia, nonproductive cough, multiple elevated inflammatory markers, and air-space consolidation in lung, psittacosis pneumonia should be considered, especially when beta-lactam antibiotics showed limited efficacy.

A bstract In this work, we bootstrap the 4-point correlators on the 1D celestial circle using 3D symmetries in the Aharony-Bergman-Jafferis-Maldacena theory as constraints. We find that the dual inversion property is strong enough to replace the crossing symmetry condition (or cyclic invariant condition) when bootstrapping. We also give some results about the conformal block expansion coefficients which contain the spectrum. Furthermore, we extract the OPE spectrum from the multi-collinear limit since all 3-point ABJM amplitudes vanish. Although we studied a specific theory, the methods used are valid for more general cases.

A bstract Celestial amplitude plays an important role in the understanding of holography. Computing celestial amplitudes by recursion can deepen our understanding of the structure of celestial amplitudes. As an important recursion method, the Berends-Giele (BG) currents on the celestial sphere are worth studying. In this paper, we study the celestial BG recursion and utilize this to calculate some typical examples. We also explore the OPE behavior of celestial BG currents. Moreover, we generalize the “sewing procedure” for BG currents to the celestial case.

Aim: Trees associating with ectomycorrhizal (ECM) fungi typically occur in infertile soils and use nutrients more conservatively than arbuscular mycorrhizal (AM) trees. We hypothesized that ECM trees would have greater nutrient resorption (i.e., proportion of nutrients resorbed during leaf senescence) than AM trees. Location: Global. Methods: We synthesized nitrogen (N) and phosphorus (P) resorption data from 378 species from sub/tropical, temperate and boreal forests, including 43 studies where ECM and AM trees co-occurred, and conducted a meta-analysis. Additionally, we quantified N resorption in 45 plots varying in ECM-AM tree abundances in the temperate deciduous forests of southern Indiana, USA. Results: Overall, resorption patterns were driven primarily by mycorrhizal type, climate zone, and to a lesser degree, leaf habit. In the boreal forest, P resorption was 76% greater for ECM than AM trees (p < .05). In the sub/tropics, AM trees resorbed 30% more N than ECM trees. At the sites where AM and ECM trees co-occurred, ECM trees resorbed more N in temperate forests (15% greater; p < .001) whereas AM trees tended to resorb more N in sub/tropical forests (by 29%; p = .08). Besides, deciduous ECM trees resorbed more N (10%) and P (15%) than deciduous AM trees, while evergreen ECM and AM trees did not differ. In the deciduous forests of Indiana, where ECM and AM trees co-occurred, the relative abundance of ECM trees in a plot was positively correlated to plot-scale N resorption (R2 = .25, p = .001), indicating greater nutrient conservatism with increasing ECM-dominance. Main conclusions: Our results indicate that mycorrhizal association – in addition to other factors – is correlated with the degree to which trees recycle nutrients, with the strongest effects occurring for N resorption by temperate deciduous trees.