A Deep Dive into Blockchain Selfish Mining

This paper studies a fundamental problem regarding the security of blockchain on how the existence of multiple misbehaving pools influences the profitability of selfish mining. Each selfish miner maintains a private chain and makes it public opportunistically for the purpose of acquiring more rewards incommensurate to his Hashrate. We establish a novel Markov chain model to characterize all the state transitions of public and private chains. The minimum requirement of Hashrate together with the minimum delay of being profitable is derived in close-form. The former reduces to 21.48% with the symmetric selfish miners, while their competition with asymmetric Hashrates puts forward a higher requirement of the profitable threshold. The profitable delay increases with the decrease of the Hashrate of selfish miners, making the mining pools more cautious on performing selfish mining.Comment: 6 pages, 13 figure

Expanded Newborn Screening for Inborn Errors of Metabolism and Genetic Characteristics in a Chinese Population

The incidence of inborn errors of metabolisms (IEMs) varies dramatically in different countries and regions. Expanded newborn screening for IEMs by tandem mass spectrometry (MS/MS) is an efficient approach for early diagnosis and presymptomatic treatment to prevent severe permanent sequelae and death. To determine the characteristics of IEMs and IEMs-associated mutations in newborns in Jining area, China, 48,297 healthy neonates were recruited for expanded newborn screening by MS/MS. The incidence of IEMs was 1/1178 in Jining, while methylmalonic acidemia, phenylketonuria, and primary carnitine deficiency ranked the top 3 of all detected IEMs. Thirty mutations in nine IEMs-associated genes were identified in 28 confirmed cases. As 19 cases with the mutations in phenylalanine hydroxylase (PAH), solute carrier family 22 member 5 (SLC22A5), and methylmalonic aciduria (cobalamin deficiency) cblC type with homocystinuria (MMACHC) genes, respectively, it suggested that mutations in the PAH, SLC22A5, and MMACHC genes are the predominant causes of IEMs, leading to the high incidence of phenylketonuria, primary carnitine deficiency, and methylmalonic acidemia, respectively. Our work indicated that the overall incidence of IEMs is high and the mutations in PAH, SLC22A5, and MMACHC genes are the leading causes of IEMs in Jining area. Therefore, it is critical to increase the coverage of expanded newborn screening by MS/MS and prenatal genetic consulting in Jining area

Aberrant expression of histone deacetylases 4 in cognitive disorders: molecular mechanisms and a potential target

Histone acetylation is a major mechanism of chromatin remodeling, contributing to epigenetic regulation of gene transcription. Histone deacetylases (HDACs) are involved in both physiological and pathological conditions by regulating the status of histone acetylation. Although histone deacetylase 4 (HDAC4), a member of the HDAC family, may lack histone deacetylase activity, it is actively involved in regulating the transcription of genes involved in synaptic plasticity, neuronal survival and neurodevelopment by interacting with transcription factors, signal transduction molecules and HDAC3, another member of the HDAC family. HDAC4 is highly expressed in brain and its homeostasis is crucial for the maintenance of cognitive function. Accumulated evidence shows that HDAC4 expression is dysregulated in several brain disorders, including neurodegenerative diseases and mental disorders. Moreover, cognitive impairment is a characteristic feature of these diseases. It indicates that aberrant HDAC4 expression plays a pivotal role in cognitive impairment of these disorders. This review aims to describe the current understanding of HDAC4’s role in the maintenance of cognitive function and its dysregulation in neurodegenerative diseases and mental disorders, discuss underlying molecular mechanisms, and provide an outlook into targeting HDAC4 as a potential therapeutic approach to rescue cognitive impairment in these diseases

A Simple Fractal-Based Model for Soil-Water Characteristic Curves Incorporating Effects of Initial Void Ratios

In this paper, a simple and efficient fractal-based approach is presented for capturing the effects of initial void ratio on the soil-water characteristic curve (SWCC) in a deformable unsaturated soil. In terms of testing results, the SWCCs (expressed by gravimetric water content) of the unsaturated soils at different initial void ratios were found to be mainly controlled by the air-entry value (Ψa), while the fractal dimension (D) could be assumed to be constant. As a result, in contrast to the complexity of existing models, a simple and efficient model with only two parameters (i.e., D and Ψa) was established for predicting the SWCC considering the effects of initial void ratio. The procedure for determining the model parameters with clear physical meaning were then elaborated. The applicability and accuracy of the proposed model were well demonstrated by comparing its predictions with four sets of independent experimental data from the tests conducted in current work, as well as the literature on a wide range of soils, including Wuhan Clay, Hefei and Guangxi expansive soil, Saskatchewan silt, and loess. Good agreements were obtained between the experimental data and the model predictions in all of the cases considered

HDAC4 in ischemic stroke: mechanisms and therapeutic potential

Abstract Stroke is one of the leading causes of death and disability worldwide, and the majority of the cases are ischemic stroke. However, it still lacks effective treatment except for thrombolytic therapy in an extremely narrow time window. Increased evidence suggests that histone deacetylase 4 (HDAC4) was dysregulated in ischemic stroke, which plays a key role in the pathogenesis of ischemic stroke and post-stroke recovery by affecting neuronal death, angiogenesis, and neurogenesis. Therefore, we aim to review the dysregulation of HDAC4 in ischemic stroke and the role of dysregulated HDAC4 in the pathogenesis of ischemic stroke. Furthermore, the therapeutic potential of modulating HDAC4 in ischemic stroke is discussed

Pyrroloquinoline quinine inhibits RANKL-mediated expression of NFATc1 in part via suppression of c-Fos in mouse bone marrow cells and inhibits wear particle-induced osteolysis in mice.

The effects of pyrroloquinoline quinine (PQQ) on RANKL-induced osteoclast differentiation and on wear particle-induced osteolysis were examined in this study. PQQ inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages (BMMs) in a dose-dependent manner without any evidence of cytotoxicity. The mRNA expression of c-Fos, NFATc1, and TRAP in RANKL-treated BMMs was inhibited by PQQ treatment. Moreover, RANKL-induced c-Fos and NFATc1 protein expression was suppressed by PQQ. PQQ additionally inhibited the bone resorptive activity of differentiated osteoclasts. Further a UHMWPE-induced murine calvaria erosion model study was performed to assess the effects of PQQ on wear particle-induced osteolysis in vivo. Mice treated with PQQ demonstrated marked attenuation of bone erosion based on Micro-CT and histologic analysis of calvaria. These results collectively suggested that PQQ demonstrated inhibitory effects on osteoclast differentiation in vitro and may suppress wear particle-induced osteolysis in vivo, indicating that PQQ may therefore serve as a useful drug in the prevention of bone loss

High-Sensitivity Raman Gas Probe for In Situ Multi-Component Gas Detection

Multiple reflection has been proven to be an effective method to enhance the gas detection sensitivity of Raman spectroscopy, while Raman gas probes based on the multiple reflection principle have been rarely reported on. In this paper, a multi-reflection, cavity enhanced Raman spectroscopy (CERS) probe was developed and used for in situ multi-component gas detection. Owing to signal transmission through optical fibers and the miniaturization of multi-reflection cavity, the CERS probe exhibited the advantages of in situ detection and higher detection sensitivity. Compared with the conventional, backscattering Raman layout, the CERS probe showed a better performance for the detection of weak signals with a relatively lower background. According to the 3σ criteria, the detection limits of this CERS probe for methane, hydrogen, carbon dioxide and water vapor are calculated to be 44.5 ppm, 192.9 ppm, 317.5 ppm and 0.67%, respectively. The results presented the development of this CERS probe as having great potential to provide a new method for industrial, multi-component online gas detection

Pyrroloquinoline quinone (PQQ) inhibits lipopolysaccharide induced inflammation in part via downregulated NF-κB and p38/JNK activation in microglial and attenuates microglia activation in lipopolysaccharide treatment mice.

Therapeutic strategies designed to inhibit the activation of microglia may lead to significant advancement in the treatment of most neurodegenerative diseases. Pyrroloquinoline quinone (PQQ) is a naturally occurring redox cofactor that acts as an essential nutrient, antioxidant, and has been reported to exert potent immunosuppressive effects. In the present study, the anti-inflammatory effects of PQQ was investigated in LPS treated primary microglia cells. Our observations showed that pretreatment with PQQ significantly inhibited the production of NO and PGE2 and suppressed the expression of pro-inflammatory mediators such as iNOS, COX-2, TNF-a, IL-1b, IL-6, MCP-1 and MIP-1a in LPS treated primary microglia cells. The nuclear translocation of NF-κB and the phosphorylation level of p65, p38 and JNK MAP kinase pathways were also inhibited by PQQ in LPS stimulated primary microglia cells. Further a systemic LPS treatment acute inflammation murine brain model was used to study the suppressive effects of PQQ against neuroinflammation in vivo. Mice treated with PQQ demonstrated marked attenuation of neuroinflammation based on Western blotting and immunohistochemistry analysis of Iba1-against antibody in the brain tissue. Indicated that PQQ protected primary cortical neurons against microglia-mediated neurotoxicity. These results collectively suggested that PQQ might be a promising therapeutic agent for alleviating the progress of neurodegenerative diseases associated with microglia activation