H 2 S epigenetic regulation of vascular cell functions

The physiological and biomedical importance of H 2 S in cardiovascular system has been extensively studied, and H 2 S is involved the regulation of vascular tone, angiogenesis, cell growth and differentiation, inflammation, and energy generation, etc. In blood vessels, cystathionine gamma-lyase (CSE) seems to be the major H 2 S-producing gene expressed in both smooth muscle and endothelium. Abnormal metabolism and functions of the CSE/H 2 S pathway have been linked to various cardiovascular diseases, including atherosclerosis and hypertension. It is known now that H 2 S posttranslationally modification of proteins by S-sulfhydration contributes to the major bioactivities of H 2 S. Cardiovascular disorders and epigenetics are closely associated, and epigenetics has become a promising field in cardiovascular research. In this research highlight, I discuss the latest published findings on H 2 S signalling in epigenetic regulation of vascular cell functions via modification of DNA methylation and DNA damage repair

Hydrogen Sulfide Regulates Energy Production to Delay Leaf Senescence Induced by Drought Stress in Arabidopsis

Hydrogen sulfide (H2S) is a novel gasotransmitter in both mammals and plants. H2S plays important roles in various plant developmental processes and stress responses. Leaf senescence is the last developmental stage and is a sequential degradation process that eventually leads to leaf death. A mutation of the H2S-producing enzyme-encoding gene L-cysteine desulfhydrase1 (DES1) leads to premature leaf senescence but the underlying mechanisms are not clear. In this present study, wild-type, DES1 defective mutant (des1) and over-expression (OE-DES1) Arabidopsis plants were used to investigate the underlying mechanism of H2S signaling in energy production and leaf senescence under drought stress. The des1 mutant was more sensitive to drought stress and displayed accelerated leaf senescence, while the leaves of OE-DES1 contained adequate chlorophyll levels, accompanied by significantly increased drought resistance. Under drought stress, the expression levels of ATPβ-1, -2, and -3 were significantly downregulated in des1 and significantly upregulated in OE-DES1, and ATPε showed the opposite trend. Senescence-associated gene (SAG) 12 correlated with age-dependent senescence and participated in the drought resistance of OE-DES1. SAG13, which was induced by environmental factors, responded positively to drought stress in des1 plants, while there was no significant difference in the SAG29 expression between des1 and OE-DES1. Using transmission electron microscopy, the mitochondria of des1 were severely damaged and bubbled in older leaves, while OE-DES1 had complete mitochondrial structures and a homogeneous matrix. Additionally, mitochondria isolated from OE-DES1 increased the H2S production rate, H2S content and ATPase activity level, as well as reduced swelling and lowered the ATP content in contrast with wild-type and des1 significantly. Therefore, at subcellular levels, H2S appeared to determine the ability of mitochondria to regulate energy production and protect against cellular aging, which subsequently delayed leaf senescence under drought-stress conditions in plants

Hydrogen Sulfide Signaling Axis as a Target for Prostate Cancer Therapeutics

Hydrogen sulfide (H2S) was originally considered toxic at elevated levels; however just in the past decade H2S has been proposed to be an important gasotransmitter with various physiological and pathophysiological roles in the body. H2S can be generated endogenously from L-cysteine by multiple enzymes, including cystathionine gamma-lyase, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase in combination with cysteine aminotransferase. Prostate cancer is a major health concern and no effective treatment for prostate cancers is available. H2S has been shown to inhibit cell survival of androgen-independent, androgen-dependent, and antiandrogen-resistant prostate cancer cells through different mechanisms. Various H2S-releasing compounds, including sulfide salts, diallyl disulfide, diallyl trisulfide, sulforaphane, and other polysulfides, also have been shown to inhibit prostate cancer growth and metastasis. The expression of H2S-producing enzyme was reduced in both human prostate cancer tissues and prostate cancer cells. Androgen receptor (AR) signaling is indispensable for the development of castration resistant prostate cancer, and H2S was shown to inhibit AR transactivation and contributes to antiandrogen-resistant status. In this review, we summarized the current knowledge of H2S signaling in prostate cancer and described the molecular alterations, which may bring this gasotransmitter into the clinic in the near future for developing novel pharmacological and therapeutic interventions for prostate cancer

WTO accession, the changing competitiveness of foreign-financed firms and regional development in Guangdong of southern China

This paper investigates the changing competitiveness of foreign-financed manufacturing firms and its implications for regional development in Guangdong province of southern China in the run-up to World Trade Organization (WTO) accession. It is argued that transnational corporations (TNCs) and some competitive, large-scale, locally-funded firms in Guangdong will triumph after WTO accession. The crowding-out process of small and medium sized enterprises (SMEs) in Guangdong will be accelerated in the near future, as they are competing directly with TNCs, and as their competitive advantages are diminishing, due to bureaucratic red tape and the rigorous enforcement of new government policies. Due to close business linkages with local privately-funded firms, the competitiveness and vitality of foreign-financed enterprises will have profound long term effects on the economic development of Guangdong, before and after WTO accession

Towards model checking Android applications

As feature-rich Android applications (apps for short) are increasingly popularized in security-sensitive scenarios, methods to verify their security properties are highly desirable. Existing approaches on verifying Android apps often have limited effectiveness. For instance, static analysis often suffers from a high false-positive rate, whereas approaches based on dynamic testing are limited in coverage. In this work, we propose an alternative approach, which is to apply the software model checking technique to verify Android apps. We have built a general framework named DroidPF upon Java PathFinder (JPF), towards model checking Android apps. In the framework, we craft an executable mock-up Android OS which enables JPF to dynamically explore the concrete state spaces of the tested apps; we construct programs to generate user interaction and environmental input so as to drive the dynamic execution of the apps; and we introduce Android specific reduction techniques to help alleviate the state space explosion. DroidPF focuses on common security vulnerabilities in Android apps including sensitive data leakage involving a non-trivial flow- and context-sensitive taint-style analysis. DroidPF has been evaluated with 131 apps, which include real-world apps, third-party libraries, malware samples and benchmarks for evaluating app analysis techniques like ours. DroidPF precisely identifies nearly all of the previously known security issues and nine previously unreported vulnerabilities/bugs.NRF (Natl Research Foundation, S’pore

Combined effects of penetration and explosion on damage characteristics of a mass concrete target

With the development of the precision guidance technology, the earth-penetrating weapon (EPW) is a huge threat to infrastructures. The objective of this research is to investigate the damage characteristics of mass concrete targets under the combined action of penetration and explosion. The validity of the penetration model is discussed by reproducing a previous experimental test reported in the literature. Meanwhile, a field test about the internal explosion in a concrete cube is conducted to verify the validity of the internal explosion model. Subsequently, damage characteristics of a mass concrete target from the upper part of a concrete gravity dam are discussed when subjected to the combined action of the penetration and explosion. In order to improve the structural performance of the mass concrete target to penetration and explosion loadings, high strength concrete material is selected as a preventive measure. Penetration processes and damage patterns of the mass target with normal and high strength concrete material are compared. Then, three internal explosion models are presented to investigate the influence of the initial penetration damage on the failure characteristics of the mass concrete target. The results show that the resistance of the mass target to the combined action of the penetration and explosion can be enhanced significantly by using the high strength concrete material. The initial penetration damage has a significant influence on the damage processes of the mass concrete target subjected to internal blast loading

Interaction of H 2 S with Calcium Permeable Channels and Transporters

A growing amount of evidence has suggested that hydrogen sulfide (H 2 S), as a gasotransmitter, is involved in intensive physiological and pathological processes. More and more research groups have found that H 2 S mediates diverse cellular biological functions related to regulating intracellular calcium concentration. These groups have demonstrated the reciprocal interaction between H 2 S and calcium ion channels and transporters, such as L-type calcium channels (LTCC), T-type calcium channels (TTCC), sodium/calcium exchangers (NCX), transient receptor potential (TRP) channels, -adrenergic receptors, and N-methyl-D-aspartate receptors (NMDAR) in different cells. However, the understanding of the molecular targets and mechanisms is incomplete. Recently, some research groups demonstrated that H 2 S modulates the activity of calcium ion channels through protein S-sulfhydration and polysulfide reactions. In this review, we elucidate that H 2 S controls intracellular calcium homeostasis and the underlying mechanisms