CCND2 Modified mRNA Activates Cell Cycle of Cardiomyocytes in Hearts With Myocardial Infarction in Mice and Pigs.

BACKGROUND: Experiments in mammalian models of cardiac injury suggest that the cardiomyocyte-specific overexpression of CCND2 (cyclin D2, in humans) improves recovery from myocardial infarction (MI). The primary objective of this investigation was to demonstrate that our specific modified mRNA translation system (SMRTs) can induce CCND2 expression in cardiomyocytes and replicate the benefits observed in other studies of cardiomyocyte-specific CCND2 overexpression for myocardial repair. METHODS: The CCND2-cardiomyocyte-specific modified mRNA translation system (cardiomyocyte SMRTs) consists of 2 modRNA constructs: one codes for CCND2 and contains a binding site for L7Ae, and the other codes for L7Ae and contains recognition elements for the cardiomyocyte-specific microRNAs miR-1 and miR-208. Thus, L7Ae suppresses CCND2 translation in noncardiomyocytes but is itself suppressed by endogenous miR-1 and -208 in cardiomyocytes, thereby facilitating cardiomyocyte-specific CCND2 expression. Experiments were conducted in both mouse and pig models of MI, and control assessments were performed in animals treated with an SMRTs coding for the cardiomyocyte-specific expression of luciferase or green fluorescent protein (GFP), in animals treated with L7Ae modRNA alone or with the delivery vehicle, and in Sham-operated animals. RESULTS: CCND2 was abundantly expressed in cultured, postmitotic cardiomyocytes 2 days after transfection with the CCND2-cardiomyocyte SMRTs, and the increase was accompanied by the upregulation of markers for cell-cycle activation and proliferation (eg, Ki67 and Aurora B kinase). When the GFP-cardiomyocyte SMRTs were intramyocardially injected into infarcted mouse hearts, the GFP signal was observed in cardiomyocytes but no other cell type. In both MI models, cardiomyocyte proliferation (on day 7 and day 3 after treatment administration in mice and pigs, respectively) was significantly greater, left-ventricular ejection fractions (days 7 and 28 in mice, days 10 and 28 in pigs) were significantly higher, and infarcts (day 28 in both species) were significantly smaller in animals treated with the CCND2-cardiomyocyte SMRTs than in any other group that underwent MI induction. CONCLUSIONS: Intramyocardial injections of the CCND2-cardiomyocyte SMRTs promoted cardiomyocyte proliferation, reduced infarct size, and improved cardiac performance in small and large mammalian hearts with MI.

Effects of Ethanol Extracts from Grateloupia elliptica, a Red Seaweed, and Its Chlorophyll Derivative on 3T3-L1 Adipocytes: Suppression of Lipid Accumulation through Downregulation of Adipogenic Protein Expression.

Grateloupia elliptica (G. elliptica) is a red seaweed with antioxidant, antidiabetic, anticancer, anti-inflammatory, and anticoagulant activities. However, the anti-obesity activity of G. elliptica has not been fully investigated. Therefore, the effect of G. elliptica ethanol extract on the suppression of intracellular lipid accumulation in 3T3-L1 cells by Oil Red O staining (ORO) was evaluated. Among the eight red seaweeds tested, G. elliptica 60% ethanol extract (GEE) exhibited the highest inhibition of lipid accumulation. GEE was the only extract to successfully suppress lipid accumulation among ethanol extracts from eight red seaweeds. In this study, we successfully isolated chlorophyll derivative (CD) from the ethyl acetate fraction (EA) of GEE by high-performance liquid chromatography and evaluated their inhibitory effect on intracellular lipid accumulation in 3T3-L1 adipocytes. CD significantly suppressed intracellular lipid accumulation. In addition, CD suppressed adipogenic protein expression such as sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (C/EBP-α), and fatty acid binding protein 4 (FABP4). Taken together, our results indicate that CD from GEE inhibits lipid accumulation by suppressing adipogenesis via the downregulation of adipogenic protein expressions in the differentiated adipocytes. Therefore, chlorophyll from G. elliptica has a beneficial effect on lipid metabolism and it could be utilized as a potential therapeutic agent for preventing obesity.

Anti-Inflammatory Effects of Sulfated Polysaccharide from Sargassum Swartzii in Macrophages via Blocking TLR/NF-Κb Signal Transduction.

This study involves enzymatic extraction of fucoidan from Sargassum swartzii and further purification via ion-exchange chromatography. The chemical and molecular characteristics of isolated fucoidan is evaluated concerning its anti-inflammatory potential in RAW 264.7 macrophages under LPS induced conditions. Structural properties of fucoidan were assessed via FTIR and NMR spectroscopy. NO production stimulated by LPS was significantly declined by fucoidan. This was witnessed to be achieved via fucoidan acting on mediators such as iNOS and COX-2 including pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), with dose dependent down-regulation. Further, the effect is exhibited by the suppression of TLR mediated MyD88, IKK complex, ultimately hindering NF-κB and MAPK activation, proposing its therapeutic applications in inflammation related disorders. The research findings provide an insight in relation to the sustainable utilization of fucoidan from marine brown algae S. swartzii as a potent anti-inflammatory agent in the nutritional, pharmaceutical, and cosmeceutical sectors.

ELM2-SANT Domain-Containing Scaffolding Protein 1 Regulates Differentiation and Maturation of Cardiomyocytes Derived From Human-Induced Pluripotent Stem Cells.

BACKGROUND: ELMSAN1 (ELM2-SANT domain-containing scaffolding protein 1) is a newly identified scaffolding protein of the MiDAC (mitotic deacetylase complex), playing a pivotal role in early embryonic development. Studies on Elmsan1 knockout mice showed that its absence results in embryo lethality and heart malformation. However, the precise function of ELMSAN1 in heart development and formation remains elusive. To study its potential role in cardiac lineage, we employed human-induced pluripotent stem cells (hiPSCs) to model early cardiogenesis and investigated the function of ELMSAN1. METHODS AND RESULTS: We generated ELMSAN1-deficient hiPSCs through knockdown and knockout techniques. During cardiac differentiation, ELMSAN1 depletion inhibited pluripotency deactivation, decreased the expression of cardiac-specific markers, and reduced differentiation efficiency. The impaired expression of genes associated with contractile sarcomere structure, calcium handling, and ion channels was also noted in ELMSAN1-deficient cardiomyocytes derived from hiPSCs. Additionally, through a series of structural and functional assessments, we found that ELMSAN1-null hiPSC cardiomyocytes are immature, exhibiting incomplete sarcomere Z-line structure, decreased calcium handling, and impaired electrophysiological properties. Of note, we found that the cardiac-specific role of ELMSAN1 is likely associated with histone H3K27 acetylation level. The transcriptome analysis provided additional insights, indicating maturation reduction with the energy metabolism switch and restored cell proliferation in ELMSAN1 knockout cardiomyocytes. CONCLUSIONS: In this study, we address the significance of the direct involvement of ELMSAN1 in the differentiation and maturation of hiPSC cardiomyocytes. We first report the impact of ELMSAN1 on multiple aspects of hiPSC cardiomyocyte generation, including cardiac differentiation, sarcomere formation, calcium handling, electrophysiological maturation, and proliferation.

The Effect of Distributional Restrictions in Speech Perception: A Case Study From Korean and Taiwanese Southern Min.

In Korean, voiced oral stops can occur intervocalically as allophones of their voiceless lenis counterparts; they can also occur initially as variants of nasal stops as a result of initial denasalization (e.g., /motu/→[bodu] "all"). However, neither [ŋ] nor [ɡ] (the denasalized variant of the velar nasal) is allowed in the initial position due to the phonotactic restriction against initial [ŋ] in Korean. Given the distribution of nasal and voiced stops in Korean, this study draws on the idea of cue informativeness, exploring (a) whether Korean listeners' attention to nasality and voicing cues is based on the distributional characteristics of nasal and voiced stops, and (b) whether their attention can be generalized across different places of articulation without such linguistic experience. In a forced-choice identification experiment, Korean listeners were more likely than Taiwanese listeners to perceive items on the voiced oral-to-nasal stop continua as nasal when they occurred in the initial position than in the intervocalic position, with the exception of velar stops. The results demonstrate that the Korean listeners attended to the nasality cue more reliably in the medial position than in the initial position, since the nasality cue in this position is less informative due to initial denasalization. Two additional forced-choice identification experiments suggested that upon hearing initial velar nasal [ŋ], Korean listeners variably employed different perceptual strategies (i.e., vowel insertion and place change) to repair the phonotactic illegality. These findings provide support for exemplar models of speech perception in which cue attention is specific to the position of a word, and to segments rather than to features.

The Effect of Lexicality, Frequency, and Markedness on Mandarin Tonal Categorization.

While the Ganong lexicality effect has been observed for phonemic and tonal categorization, the effects of frequency and markedness are less clear, especially in terms of tonal categorization. In this study, we use Mandarin Chinese to investigate the effects of lexicality, tone frequency and markedness. We examined Mandarin speakers' tonal categorization of tokens on all possible tonal continua with one end being a word and the other being a tonotactic gap (i.e., an unattested syllable-tone combination). The results of a forced-choice identification experiment showed a general bias against the gap endpoints, with the noted exception of continua involving T4 (X51), the most frequent lexical tone. Specifically, when T4 served as the gap endpoint, no obvious bias against it was observed regardless of its lexical status. Moreover, on the T3-T4 continua, there was an apparent bias against T3 (X214), the tone with the most complex contour, again, regardless of lexicality, suggesting a strong markedness effect. Taken together, the results of this study show the individual effects of lexicality, tone frequency and markedness, as well as their interactions, which contribute to our understanding of tonal categorization in relation to lexical statistics (tone frequency) and phonology (markedness).

The Sequence Recall Task and Lexicality of Tone: Exploring Tone "Deafness".

Many perception and processing effects of the lexical status of tone have been found in behavioral, psycholinguistic, and neuroscientific research, often pitting varieties of tonal Chinese against non-tonal Germanic languages. While the linguistic and cognitive evidence for lexical tone is therefore beyond dispute, the word prosodic systems of many languages continue to escape the categorizations of typologists. One controversy concerns the existence of a typological class of "pitch accent languages," another the underlying phonological nature of surface tone contrasts, which in some cases have been claimed to be metrical rather than tonal. We address the question whether the Sequence Recall Task (SRT), which has been shown to discriminate between languages with and without word stress, can distinguish languages with and without lexical tone. Using participants from non-tonal Indonesian, semi-tonal Swedish, and two varieties of tonal Mandarin, we ran SRTs with monosyllabic tonal contrasts to test the hypothesis that high performance in a tonal SRT indicates the lexical status of tone. An additional question concerned the extent to which accuracy scores depended on phonological and phonetic properties of a language's tone system, like its complexity, the existence of an experimental contrast in a language's phonology, and the phonetic salience of a contrast. The results suggest that a tonal SRT is not likely to discriminate between tonal and non-tonal languages within a typologically varied group, because of the effects of specific properties of their tone systems. Future research should therefore address the first hypothesis with participants from otherwise similar tonal and non-tonal varieties of the same language, where results from a tonal SRT may make a useful contribution to the typological debate on word prosody.

Articulatory Evidence for the Syllable-final Nasal Merging in Taiwan Mandarin.

Syllable-final nasals /n/ and /ŋ/ in Taiwan Mandarin have been reported to be undergoing merging. Perceptual studies have reported that the alleged merging is context-sensitive and the merging directions are vowel-dependent. These findings have been mostly attributed to dialectal and social factors. The current study uses ultrasonography to capture postures of the entire tongue during the production of syllable-final nasals. The results, though confirming previous findings that the merging directions of syllable-final nasals are vowel-dependent, are best accounted for by the biomechanics of the tongue, as supported by computational 3D model simulations. Furthermore, for some speakers, although nasals were merged in terms of tongue posture, the degrees of nasalization of the preceding vowel were contrastive, suggesting that the merging process may be incomplete.

Ecklonia cava Extract and Its Derivative Dieckol Promote Vasodilation by Modulating Calcium Signaling and PI3K/AKT/eNOS Pathway in In Vitro and In Vivo Models.

Nitric oxide (NO), an endothelial-derived relaxing factor synthesized by endothelial nitric oxide synthase (eNOS) in endothelial cells, enhances vasodilation by modulating vascular tone. The calcium concentration critically influences eNOS activation in endothelial cells. Thus, modulation of calcium-dependent signaling pathways may be a potential therapeutic strategy to enhance vasodilation. Marine algae reportedly possess protective effects against cardiovascular disorders, including hypertension and vascular dysfunction; however, the underlying molecular signaling pathways remain elusive. In the present study, we extracted and isolated dieckol from Ecklonia cava and investigated calcium transit-enhanced vasodilation. Calcium modulation via the well-known M3 muscarinic acetylcholine receptor (AchM3R), which is linked to NO formation, was investigated and the vasodilatory effect of dieckol was verified. Our results indicated that dieckol effectively promoted NO generation via the PI3K/Akt/eNOS axis and calcium transients influenced by AchM3R. We also treated Tg(flk: EGFP) transgenic zebrafish with dieckol to assess its vasodilatory effect. Dieckol promoted vasodilation by enlarging the dorsal aorta diameter, thus regulating blood flow velocity. In conclusion, our findings suggest that dieckol modulates calcium transit through AchM3R, increases endothelial-dependent NO production, and efficiently enhances vasodilation. Thus, E. cava and its derivative, dieckol, can be considered as potential natural vasodilators.

Viperin_sv1 promotes RIG-I expression and suppresses SVCV replication through its radical SAM domain.

SVCV infection is known to activate the host's innate immune responses, including the production of interferon (IFN) and interferon-stimulated genes (ISGs). Viperin_sv1 is a novel splice variant of viperin, which is induced during SVCV infection and proves to positively regulate the IFN activation and production. However, the underlying mechanism remains unsolved. In this study, the P protein of SVCV was identified to be the key to induce the mRNA modification and production of viperin_sv1 during the virus infection. Besides, Viperin_sv1 was able to trigger the RLR signaling cascades to activate type-1 interferon response. Additional analysis revealed that viperin_sv1 promoted the stability and function of RIG-I, which result in the production of IFN and ISGs. Moreover, the central SAM domain of viperin_sv1 was demonstrated to be essential for regulating RIG-I protein expression and inducing IFN production. Furthermore, this study also showed that SVCV replication could be inhibited by the viperin_sv1 SAM domain. In conclusion, our study demonstrates that viperin_sv1 reduces the replication of SVCV by promoting the RIG-I protein expression. Our findings identified the antiviral function played by the SAM domain of viperin_sv1 and suggested an antiviral mechanism that is conserved among different species.

Fucoxanthin-rich fraction from Sargassum fusiformis alleviates particulate matter-induced inflammation in vitro and in vivo.

Particulate matter (PM) contributes to air pollution and primarily originates from unregulated industrial emissions and seasonal natural dust emissions. Fucoxanthin (Fx) is a marine natural pigment from brown macroalgae that has been shown to have various beneficial effects on health. However, the effects of Fx on PM-induced toxicities in cells and animals have not been assessed. In this study, we investigated the anti-inflammatory potential of the Fx-rich fraction (FxRF) of Sargassum fusiformis against PM-mediated inflammatory responses. The FxRF composition was analyzed by rapid-resolution liquid chromatography mass spectrometry. Fx and other main pigments were identified. FxRF attenuated the production of inflammatory components, including prostaglandin E2 (PGE2), cyclooxygenase-2, interleukin (IL)-1ß, and IL-6 from PM-exposed HaCaT keratinocytes. PM exposure also reduced the levels of nitric oxide (NO), tumor necrosis factor-α, inducible nitric oxide synthase (iNOS), and PGE2 in PM-exposed RAW264.7 macrophages. Additionally, the culture medium from PM-exposed HaCaT cells induced upregulation of NO, iNOS, PGE2, and pro-inflammatory cytokines in RAW264.7 macrophages. FxRF also significantly decreased the expression levels of factors involved in inflammatory responses, such as NO, reactive oxygen species, and cell death, in PM-exposed zebrafish embryos. These results demonstrated the potential protective effects of FxRF against PM-induced inflammation both in vitro and in a zebrafish model.

Associations of sleep duration and fruit and vegetable intake with the risk of metabolic syndrome in Chinese adults.

ABSTRACT: To understand the adverse association of short sleep duration and insufficient fruit and vegetable intake (FVI) with and their combined effect on metabolic syndrome (MetS) in Chinese adults.This cross-sectional study analyzed 7052 adults aged 18∼64 years old in 2009, with fasting blood samples collected. Participants were divided into short/normal/long sleep duration groups and sufficient/insufficient FVI groups in accordance with self-reported information. Metabolic syndrome was defined by National Cholesterol Education Program's Adult Treatment Panel III criteria.The prevalence of MetS among the study subjects was 21.74%. Participants were classified into short (<7 h/d), normal (7∼9 h/d), and long (>9 h/d) groups according to their daily sleep duration. Participants with less than 500 g of FVI per day was considered as insufficient FVI. After adjusting for confounders, the negative effect of short sleep duration on MetS was statistically significant, with an OR of 1.29 (95%CI = 1.06∼1.56); and high fasting glucose levels were significantly associated with insufficient FVI. Compared with subjects with normal sleep duration and sufficient FVI, participants with short sleep time and insufficient FVI had the highest risk of MetS (OR = 1.37, 95% CI: 1.04-1.66).This study revealed that insufficient FVI and short sleep duration were significantly associated with an increased risk of MetS among Chinese adults. Increasing FVI and normal sleep duration during Chinese adults could be significant targets for reducing the prevalence of MetS.

Relationship between sedentary behaviour and anxiety symptoms among youth in 24 low- and middle-income countries.

BACKGROUND: Anxiety is burdensome and common in youth. Sedentary behaviour has been identified as potentially modifiable dangerous factors for many diseases. Nevertheless, little is known about the relationship between sedentary behaviour and the risk of anxiety symptoms in youth. Therefore, we aimed to examine the association among youth in 24 low- and middle-income countries (LMICs). METHODS: Data from the Global School-based Student Health Survey (GSHS) were analyzed in 59587 youth aged 12-15 years. Most of the country-wide data were nationally representative. Anxiety symptoms were self-reported. Multivariable logistic regression and meta-analyses of country-wise estimates were conducted. RESULTS: The prevalence of anxiety symptoms was 10.3%. Countrywide meta-analysis demonstrated that sedentary behaviour of >2 h/day (vs.≤2 h/day) was associated with an increased risk of anxiety symptoms (OR = 1.22; 95% CI = 1.10-1.37). CONCLUSIONS: This study provides multi-national evidence of the dangerous effect of sedentary behaviour against anxiety symptoms among youth in LMICs. Decreasing the level of sedentary behaviour during adolescence could be an important target for reducing the prevalence of anxiety.

Fucoidan from acid-processed Hizikia fusiforme attenuates oxidative damage and regulate apoptosis.

We had observed in our previous study that the active fucoidan (JHCF4), isolated from the crude fucoidan in acid-processed Hizikia fusiforme, possessed an anticancer effect. In this study, the antioxidant effect of JHCF4 was evaluated. Among the fractions, JHCF4 showed the highest scavenging activity against 2, 2-diphenyl-1-picrylhydrazyl (DPPH), alkyl, and hydroxyl radicals, as well as protective effect against reactive oxygen species (ROS) in 2, 2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-treated Vero cells. Furthermore, JHCF4 showed a protective activity against AAPH-induced apoptosis, as observed by nuclear staining with Hoechst 33342. Our results showed that JHCF4 can up-regulate Bcl-xL, down-regulate Bax and cleave caspase-3 with increased concentrations in AAPH-induced Vero cells. JHCF4 induced anti-apoptosis via a mitochondria-mediated pathway. Additionally, JHCF4 was selected for further in vivo screening in a zebrafish model, which markedly decreased ROS generation and lipid peroxidation. Thus, JHCF4 showed a potential protective activity against AAPH-induced ROS both in vitro and in the zebrafish model.

Synthesis of magnetic CoFe2O4/ordered mesoporous carbon nanocomposites and application in Fenton-like oxidation of rhodamine B.

CoFe2O4/ordered mesoporous carbon (OMC) nanocomposites were synthesized and tested as heterogeneous peroxymonosulfate (PMS) activator for the removal of rhodamine B. Characterization confirmed that CoFe2O4 nanoparticles were tightly bonded to OMC, and the hybrid catalyst possessed high surface area, pore volume, and superparamagnetism. Oxidation experiments demonstrated that CoFe2O4/OMC nanocomposites displayed favorable catalytic activity in PMS solution and rhodamine B degradation could be well described by pseudo-first-order kinetic model. Sulfate radicals (SO4-·) were verified as the primary reactive species which was responsible for the decomposition of rhodamine B. The optimum loading ratio of CoFe2O4 and OMC was determined to be 5:1. Under optimum operational condition (catalyst dosage 0.05 g/L, PMS concentration 1.5 mM, pH 7.0, and 25 °C), CoFe2O4/OMC-activated peroxymonosulfate system could achieve almost complete decolorization of 100 mg/L rhodamine B within 60 min. The enhanced catalytic activity of CoFe2O4/OMC nanocomposites compared to that of CoFe2O4 nanoparticles could be attributable to the increased adsorption capacity and accelerated redox cycles between Co(III)/Co(II) and Fe(III)/Fe(II).

Fish Oil Reduces Hepatic Injury by Maintaining Normal Intestinal Permeability and Microbiota in Chronic Ethanol-Fed Rats.

The aim of this study was to investigate the ameliorative effects of fish oil on hepatic injury in ethanol-fed rats based on the intestinal permeability and microbiota. Rats were assigned to 6 groups and fed either a control diet or an ethanol diet such as C (control), CF25 (control with 25% fish oil), CF57 (control with 57% fish oil), E (ethanol), EF25 (ethanol with 25% fish oil), and EF57 (ethanol with 57% fish oil) groups. Rats were sacrificed at the end of 8 weeks. Plasma aspartate aminotransferase (AST) and aminotransferase (ALT) activities, hepatic cytokines, and plasma endotoxin levels were significantly higher in the E group. In addition, hepatic histopathological analysis scores in the E group were significantly elevated. Rats in the E group also showed increased intestinal permeability and decreased numbers of fecal Bifidobacterium. However, plasma AST and ALT activities and hepatic cytokine levels were significantly lower in the EF25 and EF57 groups. Histological changes and intestinal permeability were also improved in the EF25 and EF57 groups. The fecal Escherichia coli numbers were significantly lower, but fecal Bifidobacterium numbers were significantly higher in the EF25 and EF57 groups.

[Heterogeneous Activation of Peroxymonosulfate with Three-dimensional Ordered Mesoporous Co3O4 for the Degradation of Rhodamine B].

Three-dimensional ordered mesoporous Co3O4 was prepared by nanocasting method with porous silicon KIT-6 as the hard template and firstly used to activate peroxymonosulfate for the degradation of rhodamine B. The structural properties were characterized by BET, H-TEM, XRD, XPS, FT-IR. The results showed that three-dimensional ordered mesoporous Co3O4 presented far superior catalytic activity over conventional nanoscale Co3O4 due to its abundant space mesoporous channel structure and the large specific surface areas. Higher catalyst dosage and higher peroxymonosulfate concentration favored the decolorization of rhodamine B. The removal of rhodamine B could be accelerated in the presence of Cl- and H2PO4-; however, the decolorization of rhodamine B would be inhibited in the presence of NO3-, SO42- and HCO3-. Sulfate radicals were identified as the dominant active species for the decolorization of rhodamine B through radicals quenching experiments. Three-dimensional ordered mesoporous Co3O4 showed excellent catalytic activity even after five consecutive cycles.

Association between air pollutants and cardiovascular disease mortality in Wuhan, China.

We examined the associations of daily mean concentrations of ambient air pollutants (particulate matter (PM10), sulfur dioxide (SO2), nitric oxide (NO2)) and daily cardiovascular diseases (CVD) mortality in Wuhan, China using a case-crossover design to analyze four years of data (2006-2009) collected from the Hubei Provincial Center for Disease Control and Prevention and the Wuhan Environmental Protection Bureau. From 2006 to 2009, daily average concentrations of PM10, SO2 and NO2 were 115.60 µg/m3, 53.21 µg/m3 and 53.08 µg/m3, respectively. After adjusting for temperature and relative humidity, a 10 µg/m3 increase in SO2 and NO2 over a 24-h period was associated with CVD mortality relative risk (R.R.) of 1.010 (95% CI: 1.000, 1.020) for SO2 and 1.019 (95% CI: 1.005, 1.033) for NO2, but there was no significant association between increases in PM10 and mortality. Subgroup analysis on by gender showed a significant association of 1.026 (95% CI: 1.007, 1.045) between NO2 and CVD among males, while no significant statistical effect was shown among females. Subgroup analysis by age showed that for those older than 65 years, every 10 µg/m3 increase in NO2 was associated with a 1.6% (95% CI: 0.1%, 3.1%) increase in CVD mortality. Subgroup analysis on different types of CVD showed that every 10 µg/m3 increase in PM10 and SO2 were significantly associated with an approximately 1.012 (95% CI: 1.002, 1.022) and 1.021 (95% CI: 1.002, 1.040) increase, respectively, in ischemic heart disease (ICH) mortality. In conclusion, exposure to NO2 is significantly associated with CVD mortality. Larger, multi-center studies in Chinese cities are being currently conducted to validate these findings.

New developments in small molecular compounds for anti-hepatitis C virus (HCV) therapy.

Infection with hepatitis C virus (HCV) affects approximately 170 million people worldwide. However, no vaccine or immunoglobulin is currently available for the prevention of HCV infection. The standard of care (SOC) involving pegylated interferon-α (PEG-IFN α) plus ribavirin (RBV) for 48 weeks results in a sustained virologic response in less than 50% of patients with chronic hepatitis C genotype 1, the most prevalent type of HCV in North America and Europe. Recently, reliable in vitro culture systems have been developed for accelerating antiviral therapy research, and many new specifically targeted antiviral therapies for hepatitis C (STAT-C) and treatment strategies are being evaluated in clinical trials. These new antiviral agents are expected to improve present treatment significantly and may potentially shorten treatment duration. The aim of this review is to summarize the current developments in new anti-HCV drugs.