Peroxynitrite imaging in ferroptosis-mediated drug-induced liver injury with a near-infrared fluorescence probe.

BACKGROUND: Over-consumption of drugs can result in drug-induced liver damage (DILI), which can worsen liver failure. Numerous studies have shown the significant role ferroptosis plays in the pathophysiology of DILI, which is typified by a marked imbalance between the generation and breakdown of lipid reactive oxygen species (ROS). The content of peroxynitrite (ONOO-) rapidly increased during this process and was thought to be a significant marker of early liver injury. Therefore, the construction of fluorescence probe for the detection and imaging of ONOO- holds immense importance in the early diagnosis and treatment of ferroptosis-mediated DILI. RESULTS: We designed a probe DILI-ONOO based on the ICT mechanism for the purpose of measuring and visualizing ONOO- in ferroptosis-mediated DILI processes and associated studies. This probe exhibited significant fluorescence changes with good sensitivity, selectivity, and can image exogenous and endogenous ONOO- in cells with low cytotoxicity. Using this probe, we were able to show changes in ONOO- content in ferroptosis-mediated DILI cells and mice models induced by the intervention of acetaminophen (APAP) and isoniazid (INH). By measuring the concentration of ferroptosis-related indicators in mice liver tissue, we were able to validate the role of ferroptosis in DILI. It is worth mentioning that compared to existing alanine transaminase (ALT) and aspartate aminotransferase (AST) detection methods, this probe can achieve early identification of DILI prior to serious liver injury. SIGNIFICANCE: This work has significant reference value in researching the relationship between ferroptosis and DILI and visualizing research. The results indicate a strong correlation between the progression of DILI and ferroptosis. Additionally, the use of DILI-ONOO shows promise in investigating the DILI process and assessing the effectiveness of medications in treating DILI.

Plasma metal concentrations and their interactions with genetic susceptibility on homocysteine levels.

Limited studies have evaluated the associations of multiple metal exposures with homocysteine (Hcy) levels, which were independent risk factor for cardiovascular disease (CVD). Furthermore, the interactions between genetic variants and plasma metals in relation to Hcy levels were largely unknown. We aimed to explore the associations of multiple plasma metals (including metalloids arsenic [As] and selenium [Se]) with Hcy levels and whether their associations were modified by genetic susceptibility. We included 2989 participants from the baseline of the Dongfeng-Tongji cohort (DFTJ cohort) and conducted a cross-sectional study to explore the associations of 17 plasma metals with serum Hcy levels. Both multi-variable linear regression model (single-metal model) and LASSO penalized regression model (multiple-metal model) were used to identify the Hcy-associated metals. The weighted genetic risk score (GRS) was calculated based on 18 established Hcy-associated genetic variants. For metals that were associated with Hcy, we further assessed the gene-metal interactions on Hcy levels. Among 17 metals, plasma molybdenum (Mo), strontium (Sr), and Zinc (Zn) were positively associated with Hcy levels, whereas Se was inversely associated with Hcy levels in both single- and multiple-metal models. We also observed that the genetic predisposition to Hcy significantly modified the association between plasma Se and serum Hcy levels (P for interaction = 0.003), while no significant gene-metal interactions were found for Mo, Sr, and Zn (all P for interactions > 0.05). These findings provide novel insight into the associations of the plasma concentrations of Mo, Se, Sr and Zn with Hcy levels and address the importance of Se as a potential upstream modifiable factor for the personalized prevention of elevated Hcy levels and CVD.

Alternations in the gut microbiota and metabolome with newly diagnosed unstable angina.

Gut microbiota plays an important role in coronary heart disease, but its compositional and functional changes in unstable angina (UA) remain unexplored. We performed metagenomic sequencing of 133 newly diagnosed UA patients and 133 sex- and age-matched controls, and profiled the fecal and plasma metabolomes in 30 case-control pairs. The alpha diversity of gut microbiota was increased in UA patients: the adjusted odds ratios (ORs) per standard deviation increase in Shannon and Simpson indices were 1.30 (95% confidence interval, 1.01-1.70) and 1.36 (1.05-1.81), respectively. Two common species (depleted Klebsiella pneumoniae and enriched Streptococcus parasanguinis; P ≤ 0.002) and three rare species (depleted Weissella confusa, enriched Granulicatella adiacens and Erysipelotrichaceae bacterium 6_1_45; P ≤ 0.005) were associated with UA. The UA-associated gut microbiota was depleted in the pathway of L-phenylalanine degradation (P = 0.001), primarily contributed by Klebsiella pneumoniae. Consistently, we found increased circulating phenylalanine in UA patients (OR = 2.76 [1.17-8.16]). Moreover, Streptococcusparasanguinis was negatively correlated with fecal citrulline (Spearman's rs = -0.470, P = 0.009), a metabolite depleted in UA patients (OR = 0.26 [0.08-0.63]). These findings are informative to help understand the metabolic connection between gut microbiota and UA.

Exposure to polycyclic aromatic hydrocarbons, DNA methylation and heart rate variability among non-current smokers.

Polycyclic aromatic hydrocarbons (PAHs) exposure is associated with heart rate variability (HRV) reduction, a widely used marker of cardiovascular autonomic dysfunction. The role of DNA methylation in the relationship between PAHs exposure and decreased HRV is largely unknown. This study aims to explore epigenome-wide DNA methylation changes associated with PAHs exposure and further evaluate their associations with HRV alternations among non-current smokers. We measured 10 mono-hydroxylated PAHs (OH-PAHs) in urine and DNA methylation levels in blood leukocytes among participants from three panels of Chinese non-current smokers (152 in WHZH, 99 in SY, and 53 in COW). We conducted linear regression analyses between DNA methylation and OH-PAHs metabolites with adjustment for age, gender, body mass index, drinking, blood cell counts, and surrogate variables in each panel separately, and combined the results by using inverse-variance weighted fixed-effect meta-analysis to obtain estimates of effect size. The median value of total OH-PAHs ranged from 0.92 × 10-2 in SY panel (62.6% men) to 13.82 × 10-2 µmol/mmol creatinine in COW panel (43.4% men). The results showed that methylation levels of cg18223625 (COL20A1) and cg07805771 (SLC16A1) were significantly or marginally significantly associated with urinary 2-hydroxynaphthalene [ß(SE) = 0.431(0.074) and 0.354(0.068), FDR = 0.016 and 0.056, respectively], while methylation level of cg09235308 (PLEC1) was positively associated with urinary total OH-PAHs [ß(SE) = 0.478(0.079), FDR = 0.004]. Hypermethylations of cg18223625, cg07805771, and cg09235308 were inversely associated with HRV indices among the WHZH and COW non-current smokers. However, we did not observe significant epigenome-wide associations for the other 9 urinary OH-PAHs. These findings provide new evidence that PAHs exposure is linked to differential DNA methylation, which may help better understand the influences of PAHs exposure on HRV alternations.

Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear. METHODS: We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study. RESULTS: We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02-1.48; P = 0.03). CONCLUSIONS: We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.

Associations of plasma metal concentrations with the decline in kidney function: A longitudinal study of Chinese adults.

Metals are widespread pollutants in the environment which have been reported to be associated with kidney dysfunction in many existing epidemiological studies. However, most of the studies are cross-sectional design and mainly focus on several toxic metals including arsenic, lead and cadmium. Therefore, we conducted this prospective study within the Dongfeng-Tongji cohort to evaluate the associations of plasma multiple metals with the decline in kidney function among Chinese middle-aged and elderly. In total, 1434 participants free of chronic diseases at baseline were included in analysis. We measured baseline plasma concentrations of 23 metals and calculated estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on serum creatinine, age, sex and ethnicity. Bonferroni correction was used for multiple testing to reduce the probability of a type I error. Principal component analysis was conducted to evaluate the combined effect of multiple metal co-exposure. Most of the plasma metal concentrations were within the literature reported reference values, whereas the concentration of lead and nickel exceeded the guideline value. We found that plasma concentrations of aluminum, arsenic, barium, lead, molybdenum, rubidium, strontium, vanadium and zinc were significantly associated with the decline in kidney function measured by annual eGFR decline, rapid renal function decline (defined as an annual decline in eGFR ≥ 5 mL/min/1.73 m2) or incident eGFR < 60 mL/min/1.73 m2, with the adjusted beta coefficients (95% CI) for annual eGFR decline 0.50 (0.30, 0.69), 0.98 (0.74, 1.23), 0.56 (0.32, 0.79), 0.21 (0.03, 0.39), 0.35 (0.16, 0.54), 0.94 (0.71, 1.17), 0.37 (0.15, 0.60), 0.78 (0.54, 1.02), and 0.74 (0.57, 0.91), respectively. The metals exposures were linked with increased risks of impaired kidney function. Associations of principal components representing these metals with the decline in kidney function were significant and suggest a possible additional health risk by co-exposure. Participants engaged in manufacturing had higher plasma levels of several metals compared with those who had been involved in management- or administration-related work. Our findings suggest that exposure to multiple metals contribute to the decline in kidney function among the middle-aged and elderly. Co-exposure to multiple metals may have synergetic effect on the kidney function. Further studies are warranted to confirm our findings and clarify the potential mechanisms.

Yellow Persistent Phosphor Ba13.35Al30.7Si5.3O70:Eu2+,Tm3+ from the Energy Regulation of Rare-Earth Ions.

The luminescence properties of Ba13.35Al30.7Si5.3O70:Eu2+ and Ba13.35Al30.7Si5.3O70:Eu2+,Tm3+ phosphors are presented. After being excited by a light source, Ba13.35Al30.7Si5.3O70:Eu2+,Tm3+ phosphors emit intense yellow long persistent luminescence covering the region from 450 to 700 nm, which can last about 8 h. Thermoluminescence curves were demonstrated to analyze the trapping nature of persistent luminescence. Tm3+ is added to improve the long persistent luminescence properties of phosphors. The mechanism of persistent luminescence has been studied.

A multi-stage association study of plasma cytokines identifies osteopontin as a biomarker for acute coronary syndrome risk and severity.

Cytokines play a critical role in the pathogenesis and development of cardiovascular diseases. However, data linking cytokines to risk and severity of acute coronary syndrome (ACS) are still limited. We measured plasma profile of 280 cytokines using a quantitative protein microarray in 12 ACS patients and 16 healthy controls, and identified 15 differentially expressed cytokines for ACS. Osteopontin, chemokine ligand 23, brain derived neurotrophic factor and C-reactive protein (CRP) were further validated using immunoassay in two independent case-control studies with a total of 210 ACS patients and 210 controls. We further examined their relations with incident ACS among 318 case-control pairs nested within the Dongfeng-Tongji cohort, and found plasma osteopontin and CRP concentrations were associated with incident ACS, and the multivariable-adjusted odds ratio (95% confidence interval) was 1.29 (1.06-1.57) per 1-SD increase for osteopontin and 1.30 (1.02-1.66) for CRP, respectively. Higher levels of circulating osteopontin were also correlated with higher severity of ACS, and earlier ACS onset time. Adding osteopontin alone or in combination with CRP modestly improved the predictive ability of ACS beyond the Framingham risk scores. Our findings suggested that osteopontin might be a biomarker for incident ACS, using osteopontin adds moderately to traditional cardiovascular risk factors.

Bacterial Cellulose: A Versatile Chiral Host for Circularly Polarized Luminescence.

Materials capable of circularly polarized luminescence (CPL) have attracted considerable attention for their promising potential applications. Bacterial cellulose (BC) was characterized as having a stable right-handed twist, which makes it a potential chiral host to endow luminophores with CPL. Then, the CPL-active BC composite film was constructed by simply impregnating bacterial cellulose pellicles with dilute aqueous solutions of luminophores (rhodamine B, carbon dots, polymer dots) and drying under ambient conditions. Simple encapsulation of luminophores renders BC with circularly polarized luminescence with a dissymmetry factor of up to 0.03. The multiple chiral centers of bacterial cellulose provide a primary asymmetric environment that can be further modulated by supramolecular chemistry, which is responsible for its circular polarization ability. We further demonstrate that commercial grade paper may endow luminophores with CPL activity, which reifies the universality of the method.

Exposure to Polycyclic Aromatic Hydrocarbons and Accelerated DNA Methylation Aging.

BACKGROUND: Aging is related to an increased risk of morbidity and mortality and is affected by environmental factors. Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health outcomes; but the association of such exposure with DNA methylation aging, a novel aging marker, is unclear. OBJECTIVES: Our aim was to investigate the association of PAH exposure with methylation aging. METHODS: We trained and validated a methylation age predictor suitable for Chinese populations using whole blood methylation data in 989 Chinese and 160 Caucasians. We defined two aging indicators: δage, as methylation age minus chronological age; and aging rate, the ratio of methylation to chronological age. The association of PAH exposure with aging indicators was evaluated using linear regressions in three panels of healthy Chinese participants (N=539, among the aforementioned 989 Chinese participants) whose exposure levels were assessed by 10 urinary monohydroxy-PAH metabolites. RESULTS: We developed a methylation age predictor providing accurate predictions in both Chinese individuals and Caucasian persons (R=0.94-0.96, RMSE=3.8-4.3). Among the 10 urinary metabolites that we measured, 1-hydroxypyrene and 9-hydroxyphenanthrene were associated with methylation aging independently of other OH-PAHs and risk factors; 1-unit increase in 1-hydroxypyrene was associated with a 0.53-y increase in Δage [95% confidence interval (CI): 0.18, 0.88; false discovery rate (FDR) FDR=0.004] and 1.17% increase in aging rate (95% CI: 0.36, 1.98; FDR=0.02), whereas for 9-hydroxyphenanthrene, the increase was 0.54-y for Δage (95% CI: 0.17, 0.91; FDR=0.004), and 1.15% for aging rate (95% CI: 0.31, 1.99; FDR=0.02). The association direction was consistent across the three Chinese panels with the association magnitude correlating with the panels' exposure levels; the association was validated by methylation data of purified leukocytes. Several cytosine-phosphoguanines, including those located on FHL2 and ELOVL2, were found associated with both aging indicators and monohydroxy-PAH levels. CONCLUSIONS: We developed a methylation age predictor specific for Chinese populations but also accurate for Caucasian populations. Our findings suggest that exposure to PAHs may be associated with an adverse impact on human aging and epigenetic alterations in Chinese populations. https://doi.org/10.1289/EHP2773.

Longer time spent in bed attempting to sleep is associated with rapid renal function decline: the Dongfeng-Tongji cohort study.

INTRODUCTION: Prospective evidence on the relation between time in bed and renal dysfunction remains limited. We aimed to investigate the association of time spent in bed attempting to sleep (TSBS) with renal function decline in a middle-aged and elderly Chinese population. METHODS: About 16,733 eligible participants with a mean age of 62.3 years at baseline were included. Rapid renal function decline was defined as (baseline eGFR - revisit eGFR)/years of follow-up ≥5 mL/min per 1.73 m2/year. A total of 1738 study participants experienced rapid renal function decline after a median 4.6-year follow-up. Logistic regression models were used for multivariate analyses. RESULTS: The adjusted odds ratio (OR) of rapid renal function decline was 1.18 (95% CI: 1.02, 1.37) for TSBS ≥9 h/night compared with TSBS 7 to <8 h/night. This association remained significant (OR = 1.19, 95% CI: 1.03, 1.38) after further adjustment for sleep quality, midday napping and usage of sleeping pills. Particularly, the association appeared to be prominent in individuals with diabetes. CONCLUSIONS: Longer TSBS (≥9 h) was independently associated with an increased risk of rapid renal function decline. Our findings emphasized the importance to have optimal TSBS. Key messages Our study firstly investigated the association between time spent in bed attempting to sleep (TSBS) and renal dysfunction in Chinese adults. Compared with individuals TSBS 7 to <8 h, individuals with TSBS ≥9 h had 19% increased risk for rapid renal function decline after adjustment for multivariate confounders. The association appeared to be prominent in individuals with diabetes.

A supramolecular approach towards strong and tough polymer nanocomposite fibers.

Polymer nanocomposite fibers are important one-dimensional nanomaterials that hold promising potential in a broad range of technological applications. It is, however, challenging to organize advanced polymer nanocomposite fibers with sufficient mechanical properties and flexibility. Here, we demonstrate that strong, tough and flexible polymer nanocomposite fibers can be approached by electrospinning of a supramolecular ensemble of dissimilar and complementary components including flexible multiwalled carbon nanotubes (CNT), and stiff cellulose nanocrystals (CNC) in an aqueous poly(vinyl alcohol) (PVA) system. CNT and CNC are bridged by a water-soluble aggregation-induced-emission (AIE) molecule that forms π-π stacking with CNT via its conjugated chains, and electrostatic attraction with CNC through its positive charges leading to a soluble CNT-AIE-CNC ensemble, which further assembles with PVA through hydrogen bonds. A high level of ordering of the nanoscale building blocks combined with hydrogen bonding leads to a more efficient stress transfer path between the reinforcing unit and the polymer. The nanocomposite fiber mat is capable of selective detection of nitroaromatic explosives.

Associations of estimated glomerular filtration rate and blood urea nitrogen with incident coronary heart disease: the Dongfeng-Tongji Cohort Study.

Estimated glomerular filtration rate (eGFR) has been reported to be associated with risk of incident coronary heart disease (CHD), and blood urea nitrogen (BUN) has been shown to be a strong predictor of mortality in patients with heart failure (HF). However, such epidemiological evidence from Chinese population was still limited. We used Cox proportional-hazards regression models to investigate the associations of eGFR and BUN with risk of incident CHD in the prospective Dongfeng-Tongji (DFTJ) cohort. After fully adjusted for potential confounders, a 10-unit decline in eGFR was associated with higher risk for CHD (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.01-1.09); compared with individuals with normal eGFR levels (eGFR ≥ 90 ml/min per 1.73 m2), individuals with a mild-to-severe eGFR decline (15 to 60 ml/min per 1.73 m2) were at significantly greater risk for CHD (HR 1.25, 95% CI 1.05-1.48; P = 0.011). Compared with individuals in the lowest tertile of BUN, those in the highest tertile were at significantly greater risk for CHD (HR 1.17, 95% CI 1.03-1.33; P = 0.014). In conclusion, a mild-to-severe decline in eGFR or a raised level of BUN might be associated with increased risk of incident CHD in middle-aged and elderly Chinese populations.

LFG-500, a newly synthesized flavonoid, induces apoptosis in human ovarian carcinoma SKOV3 cells with involvement of the reactive oxygen species-mitochondria pathway.

Ovarian cancer is the main cause of gynecologic malignancy-related mortality in women. Therefore, the disease requires improvements in treatment options and in the potency of chemotherapeutic drugs. The study of apoptosis in tumor cells is an important field for cancer therapy and cancer molecular biology. It has recently been established that LFG-500, a new synthesized flavonoid with a piperazine and benzyl group substitution, has strong anticancer activity. However, its exact molecular mechanism is not fully understood. The present study aimed to examine the effects of LFG-500 on human ovarian cancer SKOV3 cells, as well as to identify its underlying mechanisms. The data showed that LFG-500 inhibited the growth of SKOV3 cells in a concentration-dependent manner. It was found that LFG-500 induced apoptosis in SKOV3 cells, detected by DAPI staining and an Annexin V/PI double-staining assay. Moreover, LFG-500 reduced caspase-3 protein expression and increased the Bcl-2-associated X protein/B-cell lymphoma 2 protein ratio. Further findings revealed that LFG-500 treatment resulted in reactive oxygen species (ROS) accumulation and loss of mitochondrial transmembrane potential. Collectively, these results demonstrated that LFG-500 efficiently induced apoptosis in SKOV3 cells, an event possibly associated with the trigging of the mitochondrial apoptotic pathway through ROS accumulation. Therefore, LFG-500 shows potential as a potent anticancer agent for the treatment of ovarian cancer.

LFG-500, a novel synthetic flavonoid, suppresses epithelial-mesenchymal transition in human lung adenocarcinoma cells by inhibiting NLRP3 in inflammatory microenvironment.

Increasing evidence indicates that inflammatory microenvironment facilitates tumor metastasis. Here, we found that LFG-500, a novel synthetic flavonoid, significantly inhibited epithelial-mesenchymal transition (EMT) in human lung adenocarcinoma A549 and H1299 cells co-cultured with LPS-challenged THP-1 cells or cultured in THP-1 cell-derived conditioned medium. Moreover, we found that TNF-α is a direct and decisive factor for promoting EMT and LFG-500 suppressed TNF-α-induced EMT and cell motility. NLRP3 knockdown inactivated NLRP3 inflammasome, which subsequently inhibited EMT and blocked cell migration, indicating that TNF-α-induced EMT requires the NLRP3 inflammasome. LFG-500 inhibited the activation of the NLRP3 inflammasome, thus inhibiting EMT. Moreover, LFG-500 treatment significantly inhibited metastasis in vivo by downregulating NLRP3 expression. Importantly, we found that NLRP3 was highly expressed in high-grade lung adenocarcinoma and that its expression was correlated with lymph node metastasis. NLRP3 and vimentin levels were significantly increased in matched metastatic lymph nodes. Moreover, a significant positive correlation was observed between their levels. Together, these results suggest that LFG-500 markedly suppresses EMT by inhibiting the NLRP3 inflammasome in the inflammatory microenvironment and that NLRP3 is a potential biomarker of lung adenocarcinoma metastasis.

Genome-Wide Analysis of DNA Methylation and Acute Coronary Syndrome.

RATIONALE: Acute coronary syndrome (ACS) is a leading cause of death worldwide. Immune functions play a vital role in ACS development; however, whether epigenetic modulation contributes to the regulation of blood immune cells in this disease has not been investigated. OBJECTIVE: We conducted an epigenome-wide analysis with circulating immune cells to identify differentially methylated genes in ACS. METHODS AND RESULTS: We examined genome-wide methylation of whole blood in 102 ACS patients and 101 controls using HumanMethylation450 array, and externally replicated significant discoveries in 100 patients and 102 controls. For the replicated loci, we further analyzed their association with ACS in 6 purified leukocyte subsets, their correlation with the expressions of annotated genes, and their association with cardiovascular traits/risk factors. We found novel and reproducible association of ACS with blood methylation at 47 cytosine-phosphoguanine sites (discovery: false discovery rate <0.005; replication: Bonferroni corrected P<0.05). The association of methylation levels at these cytosine-phosphoguanine sites with ACS was further validated in at least 1 of the 6 leukocyte subsets, with predominant contributions from CD8+ T cells, CD4+ T cells, and B cells. Blood methylation of 26 replicated cytosine-phosphoguanine sites showed significant correlation with expressions of annotated genes (including IL6R, FASLG, and CCL18; P<5.9×10-4), and differential gene expression in case versus controls corroborated the observed differential methylation. The replicated loci suggested a role in ACS-relevant functions including chemotaxis, coronary thrombosis, and T-cell-mediated cytotoxicity. Functional analysis using the top ACS-associated methylation loci in purified T and B cells revealed vital pathways related to atherogenic signaling and adaptive immune response. Furthermore, we observed a significant enrichment of the replicated cytosine-phosphoguanine sites associated with smoking and low-density lipoprotein cholesterol (Penrichment≤1×10-5). CONCLUSIONS: Our study identified novel blood methylation alterations associated with ACS and provided potential clinical biomarkers and therapeutic targets. Our results may suggest that immune signaling and cellular functions might be regulated at an epigenetic level in ACS.

LFG-500, a newly synthesized flavonoid, attenuates lipopolysaccharide-induced acute lung injury and inflammation in mice.

Acute lung injury (ALI) often causes significant morbidity and mortality worldwide. Improved treatment and effective strategies are still required for ALI patients. Our previous studies demonstrated that LFG-500, a novel synthesized flavonoid, has potent anti-cancer activities, while its anti-inflammatory effect has not been revealed. In the present study, the in vivo protective effect of LFG-500 on the amelioration of lipopolysaccharide (LPS)-induced ALI and inflammation was detected. LFG-500 attenuated LPS-induced histological alterations, suppressed the infiltration of inflammatory cells in lung tissues and bronchoalveolar lavage fluid, as well as inhibited the secretion of several inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 in lung tissues after LPS challenge. In addition, the in vitro effects and mechanisms were studied in LPS stimulated RAW 264.7 cells and THP-1 cells. LFG-500 significantly decreased the secretion and expression of TNF-α, IL-1ß, and IL-6 through inhibiting the transcriptional activation of NF-κB. Moreover, overexpression of NF-κB p65 reversed the inhibitory effect of LFG-500 on LPS-induced NF-κB activation and inflammatory cytokine secretion. Further elucidation of the mechanism revealed that p38 and JNK MAPK pathways were involved in the anti-inflammation effect of LFG-500, through which LFG-500 inhibited the classical IKK-dependent pathway and led to inactivation of NF-κB. More importantly, LFG-500 suppressed the expression and nuclear localization of NF-κB in LPS-induced ALI mice. Taken together, these results demonstrated that LFG-500 could attenuate LPS-induced ALI and inflammation by suppressing NF-κB activation, which provides new evidence for the anti-inflammation activity of LFG-500.

Genome-Wide Analysis of DNA Methylation and Cigarette Smoking in a Chinese Population.

BACKGROUND: Smoking is a risk factor for many human diseases. DNA methylation has been related to smoking, but genome-wide methylation data for smoking in Chinese populations is limited. OBJECTIVES: We aimed to investigate epigenome-wide methylation in relation to smoking in a Chinese population. METHODS: We measured the methylation levels at > 485,000 CpG sites (CpGs) in DNA from leukocytes using a methylation array and conducted a genome-wide meta-analysis of DNA methylation and smoking in a total of 596 Chinese participants. We further evaluated the associations of smoking-related CpGs with internal polycyclic aromatic hydrocarbon (PAH) biomarkers and their correlations with the expression of corresponding genes. RESULTS: We identified 318 CpGs whose methylation levels were associated with smoking at a genome-wide significance level (false discovery rate < 0.05), among which 161 CpGs annotated to 123 genes were not associated with smoking in recent studies of Europeans and African Americans. Of these smoking-related CpGs, methylation levels at 80 CpGs showed significant correlations with the expression of corresponding genes (including RUNX3, IL6R, PTAFR, ANKRD11, CEP135 and CDH23), and methylation at 15 CpGs was significantly associated with urinary 2-hydroxynaphthalene, the most representative internal monohydroxy-PAH biomarker for smoking. CONCLUSION: We identified DNA methylation markers associated with smoking in a Chinese population, including some markers that were also correlated with gene expression. Exposure to naphthalene, a byproduct of tobacco smoke, may contribute to smoking-related methylation. CITATION: Zhu X, Li J, Deng S, Yu K, Liu X, Deng Q, Sun H, Zhang X, He M, Guo H, Chen W, Yuan J, Zhang B, Kuang D, He X, Bai Y, Han X, Liu B, Li X, Yang L, Jiang H, Zhang Y, Hu J, Cheng L, Luo X, Mei W, Zhou Z, Sun S, Zhang L, Liu C, Guo Y, Zhang Z, Hu FB, Liang L, Wu T. 2016. Genome-wide analysis of DNA methylation and cigarette smoking in Chinese. Environ Health Perspect 124:966-973; http://dx.doi.org/10.1289/ehp.1509834.

Free-Standing Optically Switchable Chiral Plasmonic Photonic Crystal Based on Self-Assembled Cellulose Nanorods and Gold Nanoparticles.

Photonic crystals incorporating with plasmonic nanoparticles have recently attracted considerable attention due to their novel optical properties and potential applications in future subwavelength optics, biosensing and data storage device. Here we demonstrate a free-standing chiral plasmonic film composed of entropy-driven self-co-assembly of gold nanoparticles (GNPs) and rod-like cellulose nanocrystals (CNCs). The CNCs-GNPs composite films not only preserve the photonic ordering of the CNCs matrix but also retain the plasmonic resonance of GNPs, leading to a distinct plasmon-induced chiroptical activity and a strong resonant plasmonic-photonic coupling that is confirmed by the stationary and ultrafast transient optical response. Switchable optical activity can be obtained by either varying the incidence angle of lights, or by taking advantage of the responsive feature of the CNCs matrix. Notably, an angle-dependent plasmon resonance in chiral nematic hybrid film has been observed for the first time, which differs drastically from that of the GNPs embed in three-dimensional photonic crystals, revealing a close relation with the structure of the host matrix. The current approach for fabricating device-scale, macroscopic chiral plasmonic materials from abundant CNCs with robust chiral nematic matrix may enable the mass production of functional optical metamaterials.