wan yihong

PARP1 and PARP2 dual inhibitors, such as olaparib, have been recently FDA approved for the treatment of advanced breast and ovarian cancers. However, their effects on bone mass and bone metastasis are unknown. Here we show that olaparib increases breast cancer bone metastasis through PARP2, but not PARP1, specifically in the myeloid lineage, but not in the cancer cells. Olaparib treatment or PARP1/2 deletion promotes osteoclast differentiation and bone loss. Intriguingly, myeloid deletion of PARP2, but not PARP1, increases the population of immature myeloid cells in bone marrow, and impairs the expression of chemokines such as CCL3 through enhancing the transcriptional repression by β-catenin...

INTRODUCTION: Human respiratory syncytial virus (hRSV) is a common respiratory virus closely related to respiratory tract infection (RTI). Rapid and accurate detection of hRSV is urgently needed to reduce the high morbidity and mortality due to hRSV infection. METHODOLOGY: Here, we established a highly sensitive and specific reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay for the rapid detection of A and B group hRSV simultaneously. The specific primer sets for hRSV A and B groups were designed in the M and M2-2 gene, respectively...

The myeloid lineage consists of multiple immune cell types, such as macrophages, monocytes, and dendritic cells. It actively participates in both innate and adaptive immunity. In response to pro- or anti-inflammatory signals, these cells undergo distinct programmed metabolic changes especially in mitochondria. Pro-inflammatory signals induce not only a simple shift from oxidative phosphorylation to glycolysis, but also complicated metabolic alterations during the early and tolerant stages in myeloid cells. In mitochondria, a broken Krebs cycle leads to the accumulation of two metabolites, citrate and succinate, both of which trigger pro-inflammatory responses of myeloid cells...

Glucagon-like peptide 1 receptor (GLP-1R) agonist (Exendin-4) is a well-known agent used to improve β-cell dysfunctions via protein kinase A (PKA), but the detailed downstream molecular mechanisms are still elusive. We have now found that PKA Cα mediated- TXNIP phosphorylation and degradation played a vital role in the β-cell protective role of exendin-4. After PKA activator (Exendin-4 or FSK) treatment, PKA Cα could directly interact with TXNIP by bimolecular fluorescence complementation and Co-IP assays in INS-1 cells...

Hand, foot and mouth disease (HFMD) is a major public health concern in China. The most predominant enteroviruses that cause HFMD have traditionally been attributed to enterovirus A71 (EVA71) and coxsackievirus A16 (CVA16). Since its first large outbreak in 2008, the dominant HFMD pathogens are constantly changing. In 2013 and 2015, CVA6 exceeded both EVA71 and CVA16 to become the leading cause of HFMD in some provinces. However, there still lacks a comprehensive overview on the molecular epidemiology and evolution of HFMD-related enteroviruses at the national level...

Emerging evidence suggest that macrophage and osteoclast are two competing differentiation outcomes from myeloid progenitors. In this review, we summarize recent advances in the understanding of the molecular mechanisms controlling the polarization of macrophage and osteoclast. These include nuclear receptors/transcription factors such as peroxisome proliferator-activated receptor γ (PPARγ) and estrogen-related receptor α (ERRα), their transcription cofactor PPARγ coactivator 1-β (PGC-1β), metabolic factors such as mitochondrial complex I (CI) component NADH:ubiquinone oxidoreductase iron-sulfur protein 4 (Ndufs4), as well as transmembrane receptors such as very-low-density-lipoprotein receptor (VLDLR)...

Multimeric adaptors are broadly involved in vesicle-mediated membrane trafficking. AP2 adaptor, in particular, plays a central role in clathrin-mediated endocytosis (CME) by recruiting cargo and clathrin to endocytic sites. It is generally thought that trafficking adaptors such as AP2 adaptor assemble spontaneously. In this work, however, we discovered that AP2 adaptor assembly is an ordered process controlled by alpha and gamma adaptin binding protein (AAGAB), an uncharacterized factor identified in our genome-wide genetic screen of CME...

Loop-mediated isothermal amplification (LAMP) has been widely used in the detection of pathogens causing infectious diseases. However, mismatches between primers (especially in the 3'-end) and templates significantly reduced the amplification efficiency of LAMP, and limited its application to genetically diverse viruses. Here, we reported a novel mismatch-tolerant LAMP assay and its application in the detection of dengue viruses (DENV). The novel method features the addition of as little as 0.15 U of high-fidelity DNA polymerase to the standard 25 μl LAMP reaction mixture...

Change history: In this Letter, the citation to 'Fig. 4e, f' in the main text should be 'Fig. 3e, f'. This has not been corrected online.

Recurrent acute respiratory tract infections (ARTIs) affect a large population, yet the specific decisive factors are largely unknown. Here we study a population of 4407 children diagnosed with ARTI, comparing respiratory virome and serum cytokine profiles associated with multiple ARTIs and single ARTI during a six-year period. The relative abundance of Propionibacterium phages is significantly elevated in multiple ARTIs compared to single ARTI group. Serum levels of TIMP-1 and PDGF-BB are markedly increased in multiple ARTIs compared to single-ARTI and non-ARTI controls, making these two cytokines potential predictors for multiple ARTIs...

Quantitative PCR (qPCR) is widely used to detect viruses. However, mismatches occurring in the 3'-end of the primers reduce amplification efficiency of qPCR and limit its capacity in detection of highly variable viruses. Here, we reported a mismatch-tolerant RT-qPCR with a small amount of additional high-fidelity DNA polymerase for simultaneous detection of RSV-A and RSV-B. The novel assay had higher amplification efficiency for various variants forming mismatches with the primers than the conventional RT-qPCR, and showed good specificity and sensitivity...

Hypnosis has a therapeutic effect on substance dependence. However, its neural basis remains unclear, which impedes its further clinical applications. This study investigated the mechanisms of smoking treatment based on hypnosis from two perspectives: immediate and follow-up effects. Twenty-four smokers screened from 132 volunteers underwent hypnosis suggestion and performed a smoking-related cue task twice during functional magnetic resonance imaging (fMRI) scanning (in normal and hypnotic states). The number of cigarettes smoked per day was recorded at follow-up visits...

Abnormal nicotinamide adenine dinucleotide (NAD+ ) metabolism causes a wide spectrum of diseases. A recent study (Cell Rep. 2019;26:969-983) shows that postpartum NAD+ homeostasis is depressed. By restoring NAD+ homeostasis, maternal nicotinamide riboside (NR) supplementation during lactation enhances postpartum weight loss, as well as juvenile development and adult neurogenesis in the offspring.

Hypnosis has been shown to have treatment effects on nicotine addiction. However, the neural basis of these effects is poorly understood. This preliminary study investigated the neural mechanisms of hypnosis-based treatment on cigarette smoking, specifically, whether the hypnosis involves a top-down or bottom-up mechanism. Two groups of 45 smokers underwent a smoking aversion suggestion and viewed smoking-related pictures and neutral pictures. One group underwent functional magnetic resonance imaging scanning twice (control and hypnotic states), whereas the other group underwent two electroencephalograph sessions...

Rapamycins are immunosuppressant and anti-cancer drugs that inhibit the kinase mTOR. Clinically, they often cause bone pain, bone necrosis, and high bone turnover, yet the mechanisms are unclear. Here we show that mTORC1 activity is high in osteoclast precursors but downregulated upon RANKL treatment. Loss-of-function genetic models reveal that while early Raptor deletion in hematopoietic stem cells blunts osteoclastogenesis due to compromised proliferation/survival, late Raptor deletion in osteoclast precursors instead augments osteoclastogenesis...

Brg1/SMARCA4 serves as the ATPase and the helicase catalytic subunit for the multi-component SWI/SNF chromatin remodeling complex, which plays a pivotal role in governing chromatin structure and gene transcription. However, the upstream signaling pathways regulating Brg1 protein stability and its physiological contribution to carcinogenesis remain largely elusive. Here we report that Brg1 is a bona fide ubiquitin substrate of SCFFBW7 . We reveal that CK1δ phosphorylates Brg1 at Ser31/Ser35 residues to facilitate the binding of Brg1 to FBW7, leading to ubiquitination-mediated degradation...

Introduction: Salt stress is one of the most important abiotic stress factors which severely affect agricultural production. Osmotins and OLPs (osmotin like proteins) are kinds of proteins which were produced during plant adapting to the environmental stress. Objective: These proteins were closely related to osmotic regulation and resistance stress. They are widely distributed in plants. Their expression for these genes was induced by salt stress, which played important roles in plants responding to salt stress...

An intraoperative technique to accurately identify microscopic tumor residuals could decrease the risk of positive surgical margins. Several lines of evidence support the expression and immunotherapeutic effect of PD-1 in breast cancer. Here, we sought to develop a fluorescence-labeled PD-1 probe for in vivo breast tumor imaging and image-guided surgery. The efficacy of PD-1 monoclonal antibody (PD-1 mAb) as adjuvant immunotherapy after surgery was also assessed. PD-1-IRDye800CW was developed and examined for its application in tumor imaging and image-guided tumor resection in an immunocompetent 4T1 mouse tumor model...

Milk lipids provide a large proportion of energy, nutrients, essential fatty acids, and signaling molecules for the newborns, the synthesis of which is a tightly controlled process. Dysregulated milk lipid production and composition may be detrimental to the growth, development, health and survival of the newborns. Many genetically modified animal models have contributed to our understanding of milk lipid regulation in the lactating mammary gland. In this review, we discuss recent advances in our knowledge of the mechanisms that control milk lipid biosynthesis and secretion during lactation, and how maternal genetic and dietary defects impact milk lipid composition and consequently offspring traits...

Cytotoxin-producing Klebsiella oxytoca is the causative agent of antibiotic-associated hemorrhagic colitis (AAHC). Recently, the cytotoxin associated with AAHC was identified as tilivalline, a known pentacyclic pyrrolobenzodiazepine (PBD) metabolite produced by K. oxytoca Although this assertion of tilivalline's role in AAHC is supported by evidence from animal experiments, some key aspects of this finding appear to be incompatible with toxicity mechanisms of known PBD toxins. We therefore hypothesized that K...