Microscopic model approaches to fragmentation of nuclei and phase transitions in nuclear matter

The properties of excited nuclear matter and the quest for a phase transition which is expected to exist in this system are the subject of intensive investigations. High energy nuclear collisions between finite nuclei which lead to matter fragmentation are used to investigate these properties. The present report covers effective work done on the subject over the two last decades. The analysis of experimental data is confronted with two major problems, the setting up of thermodynamic equilibrium in a time-dependent fragmentation process and the finite size of nuclei. The present status concerning the first point is presented. Simple classical models of disordered systems are derived starting with the generic bond percolation approach. These lattice and cellular equilibrium models, like percolation approaches, describe successfully experimental fragment multiplicity distributions. They also show the properties of systems which undergo a thermodynamic phase transition. Physical observables which are devised to show the existence and to fix the order of critical behaviour are presented. Applications to the models are shown. Thermodynamic properties of finite systems undergoing critical behaviour are advantageously described in the framework of the microcanonical ensemble. Applications to the designed models and to experimental data are presented and analysed. Perspectives of further developments of the field are suggested.Comment: 150 pages including 28 figures. To be published in Phys. Rep. Corrected discussion in section 3.2.3 and new Fig.5. New caption of Fig.2

Whether Probiotic Supplementation Benefits Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis

Gut and oral microflora are important factors in the pathogenesis and development of rheumatoid arthritis (RA). Recent studies have shown that probiotic supplements have beneficial consequences on experimental arthritis in rats. However, results from randomized clinical trials on the effects of probiotics have not been consistent. The aim of this study was to systematically review the existing evidence for the effects of probiotic intervention in RA. We included randomized controlled trials (RCTs) of RA patients receiving stable treatment with disease-modifying anti-rheumatic drugs (DMARDs) that: ① were combined with additional probiotic supplements or ② were combined with either no additional supplements or only a placebo treatment. Statistical analysis was performed using Review Manager 5.3.3. Six randomized clinical trials were eligible for inclusion in the meta-analysis, with 249 participants in total. The results showed that the probiotic intervention treatment has not yet achieved significant improvement in the American College of Rheumatology 20% improvement criteria (ACR20) score and the disease activity score in 28 joints (DAS28). The laboratory index C-reactive protein (CRP) (mg·L−1) was significantly reduced in the intervention group. The expression of inflammatory cytokines tumor necrosis factor (TNF)-α and interleukine (IL)−1β was also significantly reduced, while IL-10 expression increased in the probiotic intervention groups. This article is the first systematic review and meta-analysis providing a comprehensive assessment of the benefits of treating RA with probiotics. We found that probiotic supplementation may show a limited improvement in RA therapy in existing reports because of a lack of sufficiently high-quality work on the part of clinicians. More multi-centered, large-sample RCTs are needed in order to evaluate the benefits of probiotics in RA treatment

The longitudinal and regional analysis of bleomycin-induced pulmonary fibrosis in mice by microcomputed tomography

Introduction: Microcomputed tomography (micro-CT) is powerful for assessment of the progression of lung fibrosis in animal model, but current whole lung analysis (WLA) methods are time-consuming. Here, a longitudinal and regional analysis (LRA) method was developed to assess fibrosis easily and quickly by micro-CT. Method: Firstly, we investigated the distribution pattern of lesions in BLM-induced pulmonary fibrosis mice. Then, the VOIs for LRA were selected based on the anatomical locations and we compared the robustness, accuracy, repeatability, analysis time of LRA to WLA. Additionally, LRA was applied to assess different stages of pulmonary fibrosis, and was validated with conventional endpoint measurements (such as lung hydroxyproline and histopathology). Results: The lesions of fibrosis in 66 bleomycin (BLM)-induced pulmonary fibrosis mice were mostly in the middle and upper parts of lungs. By applying LRA, the percentages of high-density voxels in selected volumes of interest (VOIs) were well correlated with that in WLA both at Day 7 and Day 21 after bleomycin induction (R2 = 0.8784 and 0.8464, respectively). The relative standard deviation (RSD) of the percentage of high-density voxels in the VOIs was lower than that of WLA (P < 0.05). The cost time of LRA was shorter than that of WLA (P < 0.05) and the accuracy of LRA was further confirmed by the histological analysis and biochemical quantification of hydroxyproline. Conclusion: LRA is probably an easier and more time-saving method to assess fibrosis formation and evaluate treatment efficacy

Macrophage biomimetic nanocarriers for anti-inflammation and targeted antiviral treatment in COVID-19

Abstract Background The worldwide pandemic of COVID-19 remains a serious public health menace as the lack of efficacious treatments. Cytokine storm syndrome (CSS) characterized with elevated inflammation and multi-organs failure is closely correlated with the bad outcome of COVID-19. Hence, inhibit the process of CSS by controlling excessive inflammation is considered one of the most promising ways for COVID-19 treatment. Results Here, we developed a biomimetic nanocarrier based drug delivery system against COVID-19 via anti-inflammation and antiviral treatment simultaneously. Firstly, lopinavir (LPV) as model antiviral drug was loaded in the polymeric nanoparticles (PLGA-LPV NPs). Afterwards, macrophage membranes were coated on the PLGA-LPV NPs to constitute drugs loaded macrophage biomimetic nanocarriers (PLGA-LPV@M). In the study, PLGA-LPV@M could neutralize multiple proinflammatory cytokines and effectively suppress the activation of macrophages and neutrophils. Furthermore, the formation of NETs induced by COVID-19 patients serum could be reduced by PLGA-LPV@M as well. In a mouse model of coronavirus infection, PLGA-LPV@M exhibited significant targeted ability to inflammation sites, and superior therapeutic efficacy in inflammation alleviation and tissues viral loads reduction. Conclusion Collectively, such macrophage biomimetic nanocarriers based drug delivery system showed favorable anti-inflammation and targeted antiviral effects, which may possess a comprehensive therapeutic value in COVID-19 treatment

RNA helicase DHX15 exemplifies a unique dependency in acute leukemia

RNA-binding proteins (RBPs) have emerged as essential regulators to control gene expression and modulate multiple cancer traits. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy derived from transformation of T-cell progenitors that normally undergo discrete steps of differentiation in the thymus. Yet implications of essential RBPs during T-cell neoplastic transformation remain largely unclear. Systematic evaluation of RBPs identifies RNA helicase DHX15, which facilitates the disassembly of spliceosome and release of lariat introns, as a T-ALL dependency factor. Functional analysis using multiple murine T-ALL models demonstrates the essential importance of DHX15 in tumor cell survival and leukemogenesis. Moreover, single-cell transcriptomics reveals that DHX15 depletion in T-cell progenitors hinders burst proliferation during CD4-CD8-(DN)-to-CD4+CD8+(DP) transition. Mechanistically, abrogation of DHX15 perturbs RNA splicing and leads to diminished levels of SLC7A6 and SLC38A5 transcripts due to intron retention, thereby suppressing glutamine import and mTORC1 activity. We further propose a DHX15 signature modulator drug ciclopirox and demonstrate prominent anti-T-ALL efficacy. Collectively, we here highlight the functional contribution of DHX15 to leukemogenesis through regulation of established oncogenic pathways. These findings also suggest a promising therapeutic approach that splicing perturbation by targeting spliceosome disassembly may achieve considerable anti-tumor efficacy

Ca

From PubMed via Jisc Publications RouterHistory: received 2018-07-24, revised 2019-05-04, accepted 2019-05-12Publication status: aheadofprintCelastrol exhibits anti-arthritic effect in rheumatoid arthritis (RA), but the role of celastrol-mediated Ca mobilization in treatment of RA remains unelucidated. Here, we illustrate the regulatory role of celastrol-induced Ca signalling in synovial fibroblasts of RA patients and adjuvant-induced arthritis (AIA) in rats. Molecular target of celastrol was determined by computational docking, Ca dynamic and functional assays on SERCA. Ca -mediated autophagy in RASFs/RAFLS and the underlying mechanism were verified by quantification of endogenous LC3-II puncta, immunoblotting, and flow cytometry with the Ca chelator (BAPTA/AM) or suitable inhibitors. The anti-arthritic effect of celastrol, autophagy induction and growth rate of synovial fibroblasts in AIA rats were monitored by microCT and immunofluorescence staining. mRNA from joint tissues of AIA rats was isolated for transcriptional analysis of inflammatory genes. The role of Ca in regulating the identified genes was investigated by knockdown of calmodulin, calpains, and calcineurin. Celastrol inhibited SERCA to induce autophagy-dependent cytotoxicity in RASFs/RAFLS via CaMKKβ-AMPK-mTOR pathway and repressed arthritis symptoms in AIA rats. BAPTA/AM hampered the in vitro and in vivo effectiveness of celastrol. Inflammatory- and autoimmunity-associated genes downregulated by celastrol in joint tissues of AIA rat were restored by BAPTA/AM. Knockdown of calmodulin, calpains, and calcineurin in RAFLS confirmed the role of Ca in celastrol-regulated gene expression. Celastrol triggered Ca signalling to induce autophagic cell death in RASFs/RAFLS and ameliorated arthritis in AIA rats mediated by calcium-dependent/-binding proteins facilitating the exploitation of anti-arthritic drugs based on manipulation of Ca signalling. [Abstract copyright: This article is protected by copyright. All rights reserved.