TWEAK-Fn14 signaling protects mice from pulmonary fibrosis by inhibiting fibroblast activation and recruiting pro-regenerative macrophages.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by excess accumulation of the extracellular matrix (ECM). The role of macrophage-fibroblast crosstalk in lung fibrogenesis is incompletely understood. Here we found that fibroblast growth factor-inducible molecule 14 (Fn14), the receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is highly induced in myofibroblasts in the lungs of IPF patients and the bleomycin-induced lung fibrosis model.

The Origin of Clonal Hematopoiesis and Its Implication in Human Diseases.

Clonal expansion of hematopoietic cells is first observed in hematological malignancies where all the leukemic cells can be traced back to a single cell carrying oncogenic alterations. Interestingly, expansion of hematopoietic clones with defined genomic alterations, including single nucleotide variants (SNVs), small insertions and deletions (indels), and large structural chromosomal alterations (CAs), is also found in the healthy population. These genomic changes often affect leukemia driver genes.

Differentiation Kinetics of Hematopoietic Stem and Progenitor Cells In Vivo Are Not Affected by β-Glucan Treatment in Trained Immunity.

Agonists of trained immunity induce epigenetic changes in hematopoietic stem and progenitor cells (HSPCs) to generate long-lasting immune protection. Although trained HSPCs generate myeloid cells with increased responsiveness to secondary challenges, whether their differentiation kinetics is affected by prior exposure to inducers of trained immunity remains elusive. Here, we used lineage tracing to examine the cell fates of endothelial protein C receptor-positive hematopoietic stem cells (EPCR HSCs) and fms-like tyrosine kinase 3-positive multipotent progenitor cells (Flt3 MPPs) in β-glucan-induced trained immunity.

Large-scale multiplexed mosaic CRISPR perturbation in the whole organism.

Here, we report inducible mosaic animal for perturbation (iMAP), a transgenic platform enabling in situ CRISPR targeting of at least 100 genes in parallel throughout the mouse body. iMAP combines Cre-loxP and CRISPR-Cas9 technologies and utilizes a germline-transmitted transgene carrying a large array of individually floxed, tandemly linked gRNA-coding units. Cre-mediated recombination triggers expression of all the gRNAs in the array but only one of them per cell, converting the mice to mosaic organisms suitable for phenotypic characterization and also for high-throughput derivation of conventional single-gene perturbation lines via breeding.

Asymmetric Stratification-Induced Polarity Loss and Coordinated Individual Cell Movements Drive Directional Migration of Vertebrate Epithelium.

Collective migration is essential for development, wound repair, and cancer metastasis. For most collective systems, "leader cells" determine both the direction and the power of the migration. It has remained unclear, however, how the highly polarized vertebrate epithelium migrates directionally during branching morphogenesis.

In situ conversion of defective Treg into SuperTreg cells to treat advanced IPEX-like disorders in mice.

Mutations disrupting regulatory T (Treg) cell function can cause IPEX and IPEX-related disorders, but whether established disease can be reversed by correcting these mutations is unclear. Treg-specific deletion of the chromatin remodeling factor Brg1 impairs Treg cell activation and causes fatal autoimmunity in mice. Here, we show with a reversible knockout model that re-expression of Brg1, in conjunction with the severe endogenous proinflammatory environment, can convert defective Treg cells into powerful, super-activated Treg cells (SuperTreg cells) that can resolve advanced autoimmunity,  with  Brg1 re-expression in a minor fraction of Treg cells sufficient for the resolution in some cases.

Effects of landscape complexity and stand factors on arthropod communities in poplar forests.

The arthropod communities are influenced by both local conditions and features of the surrounding landscape. Landscape complexity and stand factors may both influence arthropod communities in poplar forests, but the multiscale effects of these factors on poplar defoliators and natural enemies are still poorly understood. We collected poplar arthropods at 30 sampling sites within five forest landscapes in Xinjiang, China, and assessed whether landscape complexity and stand factors influence species abundance and diversity of poplar arthropods.

Impact of cooking on the antioxidant activity of spice turmeric.

Curcuminoids, as the main ingredient of turmeric, are popularly used in food additives and condiments, and are widely accepted to be beneficial for human health for their antioxidant activity. However, curcuminoids are highly susceptible in terms of thermal-induced degradation, and curry is usually boiled, roasted, or fried in the use of food additives and condiments. Thus, it is interesting to explore the effect of cooking on the antioxidant activity of curcuminoids.

A framework for identifying dysregulated chromatin regulators as master regulators in human cancer.

Motivation: Chromatin regulators (CRs) are frequently dysregulated to reprogram the epigenetic landscape of the cancer genome. However, the underpinnings of the dysregulation of CRs and their downstream effectors remain to be elucidated.

Results: Here, we designed an integrated framework based on multi-omics data to identify candidate master regulatory CRs affected by genomic alterations across eight cancer types in The Cancer Genome Atlas.

MICMIC: identification of DNA methylation of distal regulatory regions with causal effects on tumorigenesis.

Aberrant promoter methylation is a common mechanism for tumor suppressor inactivation in cancer. We develop a set of tools to identify genome-wide DNA methylation in distal regions with causal effect on tumorigenesis called MICMIC. Many predictions are directly validated by dCas9-based epigenetic editing to support the accuracy and efficiency of our tool.

Clonal analysis of lineage fate in native haematopoiesis.

Haematopoiesis, the process of mature blood and immune cell production, is functionally organized as a hierarchy, with self-renewing haematopoietic stem cells and multipotent progenitor cells sitting at the very top. Multiple models have been proposed as to what the earliest lineage choices are in these primitive haematopoietic compartments, the cellular intermediates, and the resulting lineage trees that emerge from them. Given that the bulk of studies addressing lineage outcomes have been performed in the context of haematopoietic transplantation, current models of lineage branching are more likely to represent roadmaps of lineage potential than native fate.

Neuroprotective Effects and Mechanisms of Curcumin-Cu(II) and -Zn(II) Complexes Systems and Their Pharmacological Implications.

Alzheimer's disease (AD) is the main form of dementia and has a steadily increasing prevalence. As both oxidative stress and metal homeostasis are involved in the pathogenesis of AD, it would be interesting to develop a dual function agent, targeting the two factors. Curcumin, a natural compound isolated from the rhizome of , is an antioxidant and can also chelate metal ions.

CR2Cancer: a database for chromatin regulators in human cancer.

Chromatin regulators (CRs) can dynamically modulate chromatin architecture to epigenetically regulate gene expression in response to intrinsic and extrinsic signalling cues. Somatic alterations or misexpression of CRs might reprogram the epigenomic landscape of chromatin, which in turn lead to a wide range of common diseases, notably cancer. Here, we present CR2Cancer, a comprehensive annotation and visualization database for CRs in human cancer constructed by high throughput data analysis and literature mining.

Translational Initiation at a Non-AUG Start Codon for Human and Mouse Negative Elongation Factor-B.

Negative elongation factor (NELF), a four-subunit protein complex in metazoan, plays an important role in regulating promoter-proximal pausing of RNA polymerase II (RNAPII). Genetic studies demonstrate that the B subunit of mouse NELF (NELF-B) is critical for embryonic development and homeostasis in adult tissue. We report here that both human and mouse NELF-B proteins are translated from a non-AUG codon upstream of the annotated AUG.

Clonal dynamics of native haematopoiesis.

It is currently thought that life-long blood cell production is driven by the action of a small number of multipotent haematopoietic stem cells. Evidence supporting this view has been largely acquired through the use of functional assays involving transplantation. However, whether these mechanisms also govern native non-transplant haematopoiesis is entirely unclear.

A genetic screen identifies an LKB1-MARK signalling axis controlling the Hippo-YAP pathway.

The Hippo-YAP pathway is an emerging signalling cascade involved in the regulation of stem cell activity and organ size. To identify components of this pathway, we performed an RNAi-based kinome screen in human cells. Our screen identified several kinases not previously associated with Hippo signalling that control multiple cellular processes.

[Structure determination of five trace chemical constituents from roots of Linum usitatissimum].

Objective: To investigate the trace chemical constituents from the roots of Linum usitatissimum.

Method: Isolation and purification of the trace constituents were carried out mainly by solvents extraction and macroporous adsorbing resin and silica gel column chromatography. The structures of the isolates were elucidated by extensive spectroscopic analysis,including 1D and 2D NMR, MS, and HRMS.

Human negative elongation factor activates transcription and regulates alternative transcription initiation.

The human negative elongation factor (NELF) is a four-subunit protein complex that inhibits the movement of RNA polymerase II (RNAPII) at an early elongation stage in vitro. NELF-mediated stalling of RNAPII also attenuates transcription of a number of inducible genes in human cells. To obtain a genome-wide understanding of human NELF-mediated transcriptional regulation in vivo, we carried out an exon array study in T47D breast cancer cells with transient small interfering RNA knockdown of individual NELF subunits.

[Studies on chemical constituents of roots of Linum usitatissimum].

Objective: To study the chemical constituents from the roots of Linum usitatissimum.

Method: The compounds were isolated and purified by silica gel column chromatography, their structures were elucidated by physico-chemical properties and spectroscopic data.

Result: Ten compounds were isolated and identified as vanillic acid (1), syringic acid (2), xanthine (3), vitexin (4), isovanillin (5), (E)-3,3'-dimethoxy-4,4'-dihydroxystilbene (6), tachioside (7), beta-sitosterol and stigmasterol (8 and 9) mixture, berberine (10).