A microarray accession number was inadvertently omitted from this paper. Microarray data for this paper can be found at NCBI GEO (http://www.ncbi.nlm.nih.gov/geo/) under the accession number GSE16062.
Here we show that conventional reprogramming towards pluripotency through overexpression of Oct4, Sox2, Klf4 and c-Myc can be shortcut and directed towards cardiogenesis in a fast and efficient manner. With as little as 4 days of transgenic expression of these factors, mouse embryonic fibroblasts (MEFs) can be directly reprogrammed to spontaneously contracting patches of differentiated cardiomyocytes over a period of 11-12 days. Several lines of evidence suggest that a pluripotent intermediate is not involved. Our method represents a unique strategy that allows a transient, plastic developmental state established early in reprogramming to effectively function as a cellular transdifferentiation platform, the use of which could extend beyond cardiogenesis. Our study has potentially wide-ranging implications for induced pluripotent stem cell (iPSC)-factor-based reprogramming and broadens the existing paradigm.
Mountainous evidence suggests that inflammation, cardiomyocyte apoptosis and pyroptosis are involved in the development of sepsis and sepsis-induced cardiomyopathy (SIC). Stimulator of interferon genes (STING) is an indispensable molecule that could regulate inflammation and immune response in multiple diseases. However, the role of STING in cardiovascular disease, especially SIC remains unclear. This study was designed to investigate the potential molecular mechanisms of STING in lipopolysaccharide (LPS)-induced cardiac injury using STING global knockout mice. In wild type mice and cardiomyocytes, LPS stimulation triggered the perinuclear translocation of STING, which further bound to Type-I interferons (IFN) regulatory factor 3 (IRF3) and phosphorylated IRF3. Phosphorylated (P-) IRF3 subsequently translocated into nucleus and increased the expression of NOD-like receptor protein 3 (NLRP3). Knockout of STING in mice significantly improved survival rate and cardiac function, apart from suppressing myocardial and serum inflammatory cytokines, apoptosis, as well as cardiomyocyte pyroptosis.
In vitro
experiments revealed that NLRP3 overexpression by adenovirus could offset protective effects of STING knockdown in LPS-induced cardiomyocytes. Additionally, LPS stimulation also promoted the production of intracellular reactive oxygen (ROS), which further induced the NLRP3 translocation to the cytoplasm from the nucleus. Dissociative TXNIP could directly interact with cytoplasmic NLRP3 and form inflammasome, eventually triggering cardiomyocyte injury. Collectively, our findings disclose that STING deficiency could alleviate LPS-induced SIC in mice. Hence, targeting STING in cardiomyocytes may be a promising therapeutic strategy for preventing SIC.
Induced pluripotent stem cell technology has attracted enormous interests for potential application in regenerative medicine. Here, we reported that a specific glycogen synthase kinase 3 (GSK-3) inhibitor, CHIR99021, can induce the reprogramming of mouse embryonic fibroblasts (MEFs) transduced by only Oct4 and Klf4 two factors. When combined with Parnate (also named tranylcypromine), an inhibitor of lysine-specific demethylase 1, CHIR99021 can result in the reprogramming of human primary keratinocyte transducted with Oct4 and Klf4 two factors. To our knowledge, this is the first time to generate human iPS cells from somatic cells without exogenous Sox2 expression. Our studies suggest that the GSK-3 inhibitor might have a general application to replace transcription factors in both mouse and human reprogramming.
We present a way for symmetric multiparty-controlled teleportation of an arbitrary two-particle entangled state based on Bell-basis measurements by using two Greenberger-Horne-Zeilinger states, i.e., a sender transmits an arbitrary two-particle entangled state to a distant receiver, an arbitrary one of the n + 1 agents via the control of the others in a network. It will be shown that the outcomes in the cases that n is odd or it is even are different in principle as the receiver has to perform a controlled-not operation on his particles for reconstructing the original arbitrary entangled state in addition to some local unitary operations in the former. Also we discuss the applications of this controlled teleporation for quantum secret sharing of classical and quantum information. As all the instances can be used to carry useful information, its efficiency for qubits approaches the maximal value.Horne-Zeilinger (GHZ) state |ψ L = 1 √ 2 (|1010 + |0101 ). Recently, Rigolin [17] showed a way to teleport an arbitrary two-qubit entangled state with a four-particle entangled state |ψ R = 1 2 (|0000 + |0101 + |1010 + |1111 ) and four-particle joint measurements.Recently, controlled teleporation for a single-qubit |χ = a| ↑ + b| ↓ [33,34] [35] have been studied. In those teleportation protocols, the qubits can be regenerated by one of the receivers with the help of the others. Those principles can be used to split a quantum secret in QSS [19]. In this paper, we will present a symmetric protocol for multiparty-controlled teleportation of an arbitrary two-particle entangled state with two GHZ states and
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