Interleukin-22 ameliorates liver fibrosis through miR-200a/beta-catenin

IL-22 ameliorates liver fibrosis by inhibiting hepatic stellate cells (HSC), and loss of miR-200a is associated with the development of liver fibrosis. The study aimed to investigate the interplay between IL-22 and miR-200a in regulating liver fibrosis in vivo and in vitro. We observed that IL-22 significantly reduced the proliferation of HSC and increased the expression of p-STAT3. β-catenin was identified as a target gene of miR-200a by luciferase reporter assay, and upregulation of miR-200a significantly attenuated the proliferation of HSC and reduced β-catenin expression. IL-22 treatment increased expression of miR-200a and decreased expression of β-catenin in HSC. The expression of p-STAT3 and miR-200a was elevated while β-catenin was decreased in fibrotic rat liver after IL-22 treatment. Expression levels of β-catenin and p-STAT3 were inversely correlated in fibrotic rat liver and HSC. Upregulation of β-catenin suppressed expression of p-STAT3 in HSC. We concluded that IL-22 inhibits HSC activation and ameliorates liver fibrosis through enhancing expression of miR-200a and reducing expression of β-catenin, suggesting there may be a crosstalk between IL-22/STAT3 and β-catenin pathway

Failure of early mycological clearance in HIV-negative cryptococcal meningitis

BACKGROUND: Negative cerebrospinal fluid (CSF) cultures at 2 weeks after antifungal treatment (early mycological clearance [EMC]) should be a treatment goal of cryptococcal meningitis (CM). However, EMC in human immunodeficiency virus (HIV)-negative patients with CM is poorly understood. METHODS: We conducted a retrospective review of medical records and 1-year follow-up of 141 HIV-negative patients with CM with an initial positive CSF culture for RESULTS: Of 141 patients, 28 (19.9%) had EMC failure. The 1-year mortality rate was 5.7% (8/141). Multivariate analysis showed that non-amphotericin B (AmB)-based regimens, baseline log CONCLUSIONS: EMC failure in HIV-negative CM is attributed to non-AmB-based therapy and is associated with lo

Micro-manufacturing : research, technology outcomes and development issues

Besides continuing effort in developing MEMS-based manufacturing techniques, latest effort in Micro-manufacturing is also in Non-MEMS-based manufacturing. Research and technological development (RTD) in this field is encouraged by the increased demand on micro-components as well as promised development in the scaling down of the traditional macro-manufacturing processes for micro-length-scale manufacturing. This paper highlights some EU funded research activities in micro/nano-manufacturing, and gives examples of the latest development in micro-manufacturing methods/techniques, process chains, hybrid-processes, manufacturing equipment and supporting technologies/device, etc., which is followed by a summary of the achievements of the EU MASMICRO project. Finally, concluding remarks are given, which raise several issues concerning further development in micro-manufacturing

Modern microwave methods in solid state inorganic materials chemistry: from fundamentals to manufacturing

No abstract available

Genomics and metagenomics of trimethylamine-utilizing Archaea in the human gut microbiome

International audienceThe biological significance of Archaea in the human gut microbiota is largely unclear. We recently reported genomic and biochemical analyses of the Methanomassiliicoccales, a novel order of methanogenic Archaea dwelling in soil and the animal digestive tract. We now show that these Methanomassiliicoccales are present in published microbiome data sets from eight countries. They are represented by five Operational Taxonomic Units present in at least four cohorts and phylogenetically distributed into two clades. Genes for utilizing trimethylamine (TMA), a bacterial precursor to an atherosclerogenic human metabolite, were present in four of the six novel Methanomassiliicoccales genomes assembled from ELDERMET metagenomes. In addition to increased microbiota TMA production capacity in long-term residential care subjects, abundance of TMA-utilizing Methanomassiliicoccales correlated positively with bacterial gene count for TMA production and negatively with fecal TMA concentrations. The two large Methanomassiliicoccales clades have opposite correlations with host health status in the ELDERMET cohort and putative distinct genomic signatures for gut adaptation

A Next-Generation Liquid Xenon Observatory for Dark Matter and Neutrino Physics

The nature of dark matter and properties of neutrinos are among the mostpressing issues in contemporary particle physics. The dual-phase xenontime-projection chamber is the leading technology to cover the availableparameter space for Weakly Interacting Massive Particles (WIMPs), whilefeaturing extensive sensitivity to many alternative dark matter candidates.These detectors can also study neutrinos through neutrinoless double-beta decayand through a variety of astrophysical sources. A next-generation xenon-baseddetector will therefore be a true multi-purpose observatory to significantlyadvance particle physics, nuclear physics, astrophysics, solar physics, andcosmology. This review article presents the science cases for such a detector.<br

Evolution and transmission of antibiotic resistance is driven by Beijing lineage Mycobacterium tuberculosis in Vietnam

A previous investigation has elucidated the landscape of Mtb genomic diversity and transmission dynamics in Ho Chi Minh City, Vietnam. Here, we expand the scope of this survey by adding a substantial number of additional genomes (total sample size: 2,542) and phenotypic drug susceptibility data for the majority of isolates. We aim to explore the prevalence and evolutionary dynamics of drug resistance and our ability to predict drug resistance from sequencing data. Among isolates tested phenotypically against first-line drugs, we observed high rates of streptomycin [STR, 37.7% ( N = 573/1,520)] and isoniazid resistance [INH, 25.7% ( N = 459/1,786)] and lower rates of resistance to rifampicin [RIF, 4.9% ( N = 87/1,786)] and ethambutol [EMB, 4.2% ( N = 75/1,785)]. Relative to global benchmarks, resistance to STR and INH was predicted accurately when applying the TB-Profiler algorithm to whole genome sequencing data (sensitivities of 0.81 and 0.87, respectively), while resistance to RIF and EMB was predicted relatively poorly (sensitivities of 0.70 and 0.44, respectively). Exploring the evolution of drug resistance revealed the main phylogenetic lineages to display differing dynamics and tendencies to evolve resistance via mutations in certain genes. The Beijing sublineage L2.2.1 was found to acquire de novo resistance mutations more frequently than isolates from other lineages and to suffer no apparent fitness cost acting to impede the transmission of resistance. Mutations conferring resistance to INH and STR arose earlier, on average, than those conferring resistance to RIF and are now more widespread across the phylogeny. The high prevalence of “background” INH resistance, combined with high rates of RIF mono-resistance (20.7%, N = 18/87), suggests that rapid assays for INH resistance will be valuable in this setting. These tests will allow the detection of INH mono-resistance and will allow multi-drug-resistant isolates to be distinguished from isolates with RIF mono-resistance. IMPORTANCE Drug-resistant tuberculosis (TB) infection is a growing and potent concern, and combating it will be necessary to achieve the WHO’s goal of a 95% reduction in TB deaths by 2035. While prior studies have explored the evolution and spread of drug resistance, we still lack a clear understanding of the fitness costs (if any) imposed by resistance-conferring mutations and the role that Mtb genetic lineage plays in determining the likelihood of resistance evolution. This study offers insight into these questions by assessing the dynamics of resistance evolution in a high-burden Southeast Asian setting with a diverse lineage composition. It demonstrates that there are clear lineage-specific differences in the dynamics of resistance acquisition and transmission and shows that different lineages evolve resistance via characteristic mutational pathways