The PRC2 complex epigenetically silences GATA4 to suppress cellular senescence and promote the progression of breast cancer.

BACKGROUND: The transcription factor GATA4 is pivotal in cancer development but is often silenced through mechanisms like DNA methylation and histone modifications. This silencing suppresses the transcriptional activity of GATA4, disrupting its normal functions and promoting cancer progression. However, the precise molecular mechanisms and implications of GATA4 silencing in tumorigenesis remain unclear. Here, we aim to elucidate the mechanisms underlying GATA4 silencing and explore its role in breast cancer progression and its potential as a therapeutic target. METHODS: The GATA4-breast cancer prognosis link was explored via bioinformatics analyses, with GATA4 expression measured in breast tissues. Functional gain/loss experiments were performed to gauge GATA4's impact on breast cancer cell malignancy. GATA4-PRC2 complex interaction was analyzed using silver staining and mass spectrometry. Chromatin immunoprecipitation, coupled with high-throughput sequencing, was used to identify GATA4-regulated downstream target genes. The in vitro findings were validated in an in situ breast cancer xenograft mouse model. RESULTS: GATA4 mutation and different breast cancer subtypes were correlated, suggesting its involvement in disease progression. GATA4 suppressed cell proliferation, invasion, and migration while inducing apoptosis and senescence in breast cancer cells. The GATA4-PRC2 complex interaction silenced GATA4 expression, which altered the regulation of FAS, a GATA4 downstream gene. In vivo experiments verified that GATA4 inhibits tumor growth, suggesting its regulatory function in tumorigenesis. CONCLUSIONS: This comprehensive study highlights the epigenetic regulation of GATA4 and its impact on breast cancer development, highlighting the PRC2-GATA4-FAS pathway as a potential target for therapeutic interventions in breast cancers.

Enhanced visible light photocatalytic performance of carbon and oxygen co-doped carbon nitride with a three-dimensional structure: Performance and mechanism study.

As a cost-effective photocatalyst, carbon nitride (g-C3N4) holds tremendous promise for addressing energy shortages and environmental pollution. However, its application is limited by disadvantages such as low specific surface area and easy recombination of photogenerated electron-hole pairs. This study introduces C and O co-doped g-C3N4 with a three-dimensional (3D) structure achieved through a straightforward one-step calcination process, demonstrating excellent photocatalytic activity of hydrogen production and oxytetracycline degradation, with superoxide radicals as the primary active species. We propose a plausible enhanced mechanism based on systematic characterizations and density functional theory calculations. The 3D structure confers a substantial specific surface area, enhancing both the adsorption area and active sites of catalysts while bolstering structural stability. Co-doping optimizes the band structure and electric conductivity of the catalyst, facilitating rapid migration of photogenerated charges. The synergistic effects of these enhancements significantly elevate the photocatalytic performance. This study presents a convenient and feasible method for the preparation of dual-regulated photocatalysts with outstanding performance.

Histone deacetylase 9-mediated phenotypic transformation of vascular smooth muscle cells is a potential target for treating aortic aneurysm/dissection.

Aortic aneurysm/dissection (AAD) is a serious cardiovascular condition characterized by rapid onset and high mortality rates. Currently, no effective drug treatment options are known for AAD. AAD pathogenesis is associated with the phenotypic transformation and abnormal proliferation of vascular smooth muscle cells (VSMCs). However, endogenous factors that contribute to AAD progression remain unclear. We aimed to investigate the role of histone deacetylase 9 (HDAC9) in AAD pathogenesis. HDAC9 expression was considerably increased in human thoracic aortic dissection specimens. Using RNA-sequencing (RNA-seq) and chromatin immunoprecipitation, we demonstrated that HDAC9 transcriptionally inhibited the expression of superoxide dismutase 2 and insulin-like growth factor-binding protein-3, which are critically involved in various signaling pathways. Furthermore, HDAC9 triggered the transformation of VSMCs from a systolic to synthetic phenotype, increasing their proliferation and migration abilities and suppressing their apoptosis. Consistent with these results, in vivo experiments revealed that TMP195, a pharmacological inhibitor of HDAC9, suppressed the formation of the ß-aminopropionitrile-induced AAD phenotype in mice. Our findings indicate that HDAC9 may be a novel endogenous risk factor that promotes the onset of AAD by mediating the phenotypic transformation of VSMCs. Therefore, HDAC9 may serve as a potential therapeutic target for drug-based AAD treatment. Furthermore, TMP195 holds potential as a therapeutic agent for AAD treatment.

Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection.

Thoracic aortic aneurysms (TAAs) are a major cause of death owing to weaker blood vessel walls and higher rupture rates in affected individuals. Vascular smooth muscle cells (VSMCs) are the predominant cell type within the aortic wall and their dysregulation may contribute to TAA progression. Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, is involved in several pathological processes; however, the biological functions and mechanisms underlying VSMC phenotype transition and vascular intimal hyperplasia remain unclear. The present study aimed to determine the involvement of EZH2 in mediating VSMC function in the development of TAAs. The expression of EZH2 was revealed to be elevated in patients with thoracic aortic dissection and TAA mouse model through western blotting and reverse transcription-quantitative PCR experiments. Subsequently, a mouse model was established using ß-aminopropionitrile. In vitro, EdU labeling, Transwell assay, wound healing assay and hematoxylin-eosin staining revealed that knocking down the Ezh2 gene could reduce the proliferation, invasion, migration, and calcification of mouse primary aortic smooth muscle cells. Flow cytometry analysis found that EZH2 deficiency increased cell apoptosis. Depletion of Ezh2 in mouse primary aortic VSMCs promoted the transformation of VSMCs from a synthetic to a contractile phenotype. Using RNA-sequencing analysis, it was demonstrated that Ezh2 regulated a group of genes, including integrin ß3 (Itgb3), which are critically involved in the extracellular matrix signaling pathway. qChIP found Ezh2 occupies the Itgb3 promoter, thereby suppressing the expression of Itgb3. Ezh2 promotes the invasion and calcification of VSMCs, and this promoting effect is partially reversed by co-knocking down Itgb3. In conclusion, the present study identified a previously unrecognized EZH2-ITGB3 regulatory axis and thus provides novel mechanistic insights into the pathophysiological function of EZH2. EZH2 may thus serve as a potential target for the management of TAAs.

Overexpression of Lias Gene Alleviates Cadmium-Induced Kidney Injury in Mice Involving Multiple Effects: Metabolism, Oxidative Stress, and Inflammation.

Oxidative stress is an important mechanism underlying toxicity induced by cadmium (Cd) exposure. However, there are significant differences of the antioxidant baseline in different populations. This means that different human has different intensity of oxidative stress in vivo after exposure to toxicants. LiasH/H mouse is a specific model which is created by genetically modifying the Lias 3'-untranslated region (3'-UTR). LiasH/H mice express high levels of LA and have high endogenous antioxidant capacity which is approximately 150% higher than wild-type C57BL/6 J mice (WT, Lias+/+). But more importantly, they have dual roles of metal chelator and antioxidant. Here, we applied this mouse model to evaluate the effect of endogenous antioxidant levels in the body on alleviating Cd-induced renal injury including Cd metabolism, oxidative stress, and inflammation. In the experiment, mice drank water containing Cd (50 mg/L), for 12 weeks. Many biomarkers of Cd metabolism, oxidative stress, inflammation, and major pathological changes in the kidney were examined. The results showed overexpression of the Lias gene decreased Cd burden in the body of mice, mitigated oxidative stress, attenuated the inflammatory response, and subsequent alleviated cadmium-induced kidney injury in mice.

Lias overexpression alleviates pulmonary injury induced by fine particulate matter in mice.

Oxidative stress and inflammation are mechanisms underlying toxicity induced by fine particulate matter (PM2.5). The antioxidant baseline of the human body modulates the intensity of oxidative stress in vivo. This present study aimed to evaluate the role of endogenous antioxidants in alleviating PM2.5-induced pulmonary injury using a novel mouse model (LiasH/H) with an endogenous antioxidant capacity of approximately 150% of its wild-type counterpart (Lias+/+). LiasH/H and wild-type (Lias+/+) mice were randomly divided into control and PM2.5 exposure groups (n = 10), respectively. Mice in the PM2.5 group and the control group were intratracheally instilled with PM2.5 suspension and saline, respectively, once a day for 7 consecutive days. The metal content, major pathological changes in the lung, and levels of oxidative stress and inflammation biomarkers were examined. The results showed that PM2.5 exposure induced oxidative stress in mice. Overexpression of the Lias gene significantly increased the antioxidant levels and decreased inflammatory responses induced by PM2.5. Further study found that LiasH/H mice exerted their antioxidant function by activating the ROS-p38MAPK-Nrf2 pathway. Therefore, the novel mouse model is useful for the elucidation of the mechanisms of pulmonary injury induced by PM2.5.

Effects of silver nanoparticles on maternal mammary glands and offspring development under lactation exposure.

The widespread applications of silver nanoparticles (AgNPs) throughout our daily lives have raised concerns regarding their environmental health and safety (EHS). Despite an increasing number of studies focused on the EHS impacts of AgNPs, there remain significant knowledge gaps with respect to their potential health impacts on susceptible populations, such as lactating mothers and infants. Herein, we aimed to investigate the deleterious effects of AgNPs with different sizes (20 and 40 nm) and surface coatings (PVP and BPEI) on maternal mice and their offspring following lactation exposure at doses of 20, 100 and 400 µg/kg body weight. We discovered that AgNPs could accumulate in the maternal mammary glands and disrupt the epithelial barrier in a dose-dependent manner. Notably, BPEI-coated AgNPs caused more damage to the mammary glands than PVP-coated particles. Importantly, we observed that, while AgNPs were distributed throughout the blood and main tissues, they were particularly enriched in the brains of breastfed offspring after maternal exposure during lactation, exhibiting exposure dosage- and particle coating-dependent patterns. Compared to PVP-coated nanoparticles, BPEI-coated AgNPs were more readily transferred to the offspring, possibly due to their enhanced deposition in maternal mammary glands. Moreover, we observed reduced body weight, blood cell toxicity, and tissue injuries in breastfed offspring whose dams received AgNPs. As a whole, these results reveal that maternal exposure to AgNPs results in the translocation of AgNPs into offspring via breastfeeding, inducing developmental impairments in these breastfed offspring. This study provides important new insights into the EHS impacts of AgNP consumption during lactation.

A simple, rapid method for simultaneous determination of multiple elements in serum by using an ICP-MS equipped with collision cell.

We developed an inductively coupled plasma mass spectrometry method for testing 23 elements, namely, Mg, Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Mo, Cd, Sn, Sb, Ba, W, Tl, Pb, and U, in human serum. The serum samples were analyzed after diluting 1/25 with 0.5% nitric acid, 0.02% Triton-X-100, and 2% methanol. Sc, In, Y, Tb, and Bi were assigned internal standards to correct the baseline drift and matrix interference. The kinetic energy discrimination mode of the instrument with helium gas as the collision gas eliminated polyatomic interference. All 23 elements exhibited excellent linearity in their testing range, with a coefficient of determination ≥ 0.9996. The limits of detection of the 23 elements were within the range of 0.0004-0.2232 µg/L. The intra- and inter-day precision (relative standard deviation) were < 12.19%. The recoveries of the spiked standard for all elements were 88.98-109.86%. Among the 23 elements of the serum reference materials, the measured results of Mg, Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, and Se were within the specified range of the certificate, and the results of the other elements were also satisfactory. The developed method was simple, rapid, and effective, and only 60 µL sample was consumed. A total of 1000 serum samples from healthy individuals were randomly selected from the Henan Rural Cohort, which reflects the status of serum elements in rural adults from the Northern Henan province of central China.

Mixed exposure effect of seminal metals on semen quality, mediation of total antioxidant capacity, and moderation of GSTM1/GSTT1 gene deletion in Chinese reproductive-aged men.

BACKGROUND: The effects of metal exposure on semen quality and the role of oxidative damage in this process remain unclear. METHODS: We recruited 825 Chinese male volunteers, and 12 seminal metals (Mn, Cu, Zn, Se, Ni, Cd, Pb, Co, Ag, Ba, Tl, and Fe), the total antioxidant capacity (TAC), and reduced glutathione were measured. Semen parameters and GSTM1/GSTT1-null genotypes were also detected. Bayesian kernel machine regression (BKMR) was applied to evaluate the effect of the mixed exposure to metals on semen parameters. The mediation of TAC and moderation of GSTM1/GSTT1 deletion were analyzed. RESULTS: Most seminal metal concentrations were correlated with each other. The BKMR models revealed a negative association between the semen volume and metal mixture, with Cd (cPIP = 0.60) and Mn (cPIP = 0.10) as the major contributors. Compared to fixing all scaled metals at their median value (50th percentiles), fixing the scaled metals at their 75th percentiles decreased the TAC by 2.17 units (95%CI: -2.60, -1.75). Mediation analysis indicated that Mn decreased the semen volume, with 27.82% of this association mediated by TAC. Both the BKMR and multi-linear models showed that seminal Ni was negatively correlated with sperm concentration, total sperm count, and progressive motility, which was modified by GSTM1/GSTT1. Furthermore, Ni and the total sperm count showed a negative association in GSTT1 and GSTM1 null males (ß[95%CI]: 0.328 [-0.521, -0.136]) but not in males with GSTT1 and/or GSTM1. Although Fe and the sperm concentration and total sperm count were positively correlated, they showed inverse "U" shapes in univariate analysis. CONCLUSION: Exposure to the 12 metals was negatively associated with semen volume, with Cd and Mn as the major contributors. TAC may mediate this process. GSTT1 and GSTM1 can modify the reduction in the total sperm count caused by seminal Ni exposure.

The effect of gum consumption on blood pressure as a risk factor for coronary heart disease: A meta-analysis of controlled trials.

Guar gum has been used in the management of hypercholesterolemia, constipation, weight loss, type 2 diabetes mellitus and hypertension. Our aim was to verify the hypothesis that Guar gum can be used as an alternative to pharmacological agents in the treatment of mild hypertension. Thus, we conducted a systematic review and meta-analysis to evaluate the effectiveness of Guar gum in reducing blood pressure. We searched the Cochrane Library, PubMed/Medline, Scopus and Google Scholar databases for studies published in the English language up to June 2020 which evaluated the effects of gum consumption on systolic blood pressure (SBP) and diastolic blood pressure (DBP). Nine randomized clinical trials with suitable comparison groups (placebo/control) reported SBP and DBP as outcome measures. These trials involved in total 640 participants. The overall results indicated that the consumption of gum resulted in a significant change in SBP (WMD: -1.190 mmHg, 95% CI: -2.011, -0.370) and DBP (WMD: -1.101 mmHg, 95% CI: -1.597, -0.605). Moreover, the greatest reduction in blood pressure was seen in patients with type 2 diabetes mellitus and metabolic syndrome who consumed Guar gum (WMD: -3.375 mmHg). In addition, there was a significant decrease in SBP if the gum dosage was > 15 g (WMD: -6.637 mmHg) and if the intervention duration was > 12 weeks (WMD: -1.668 mmHg). The results of the present dose-response meta-analysis support the employment of gum consumption in the reduction of SBP and DBP. Based on the sub-group analyses, we highlight that the greatest decrease in SBP was experienced if the gum dosage was > 15 g and when the intervention lasted > 12 weeks.

Alterations in the gut microbiota and its metabolic profile of PM2.5 exposure-induced thyroid dysfunction rats.

Fine particulate matter (PM2.5) has drawn more and more interest due to its adverse effects on health. Thyroid has been demonstrated to be the key organ impacted by PM2.5. However, the mechanisms for PM2.5 exposure-induced thyrotoxicity remain unclear. To explore the mechanisms, a rat thyroid injury model was established by exposing rats to PM2.5 via passive pulmonary inhalation. Thyroid hormones and thyroid function proteins were detected. The thyroid function affected by PM2.5 exposure was investigated via metabolomics analysis using liquid chromatography-mass spectrometry and 16S rRNA gene sequencing. Results showed that PM2.5 exposure induced remarkable alterations in gut microbiome evenness, richness, and composition. Metabolomics profiling revealed that the urine metabolites levels were changed by PM2.5 exposure. The altered gut microbiota and urine metabolites showed significant correlations with thyroid function indicators (total T3, total T4 and thyrotropin hormone, etc.). These metabolites were involved in metabolic pathways including thyroid hormone synthesis, metabolisms of tryptophan, d-Glutamine and D-glutamate, histidine, glutathione, etc. The altered gut microbiota showed significant correlations with urine metabolites (glutathione, citric acid, D-Glutamic acid, kynurenic acid and 5-Aminopentanoic acid, etc.). For example, the taurocholic acid levels positively correlated with the relative abundance of several genera including Elusimicrobium (r = 0.9741, p = 0.000000), Muribaculum (r = 0.9886, p = 0.000000), Candidatus_Obscuribacter (r = 0.8423, p = 0.000585), Eubacterium (r = 0.9237, p = 0.000017), and Parabacteroides (r = 0.8813, p = 0.000150), while it negatively correlated with the relative abundance of Prevotella (r = -0.8070, p = 0.001509). PM2.5 exposure-induced thyrotoxicity led to remarkable alterations both in gut microbiome composition and some metabolites involved in metabolic pathways. The altered intestinal flora and metabolites can in turn influence thyroid function in rats. These findings may provide novel insights regarding perturbations of the gut-thyroid axis as a new mechanism for PM2.5 exposure-induced thyrotoxicity.

Gene-Environment Interactions Between Environmental Response Genes Polymorphisms and Mitochondrial DNA Copy Numbers Among Benzene Workers.

OBJECTIVE: To determine the effect of mitochondrial DNA copy number (mtDNAcn) as a biomarker of benzene exposure. METHODS: A total of 294 benzene-exposed workers and 102 controls were recruited. Biomarkers of mtDNAcn, cytokinesis-block micronucleus (MN) frequency, and peripheral blood white blood cells (WBC) were detected. Eighteen polymorphism sites in DNA damage repair and metabolic genes were analyzed. RESULTS: Benzene exposure increased mtDNAcn and indicated a dose-response relationship (P < 0.001). mtDNAcn was negatively correlated with WBC count and DNA methylation and positively correlated with MN frequency. The AG type in rs1695 interacted with benzene exposure to aggravate mtDNAcn (ß = 0.006, 95% CI: 0, 0.012, P = 0.050). rs13181, rs1695, rs1800975, and GSTM1 null were associated with benzene-induced mtDNAcn. Rs1695 interacted with benzene to increase mitochondrial damage. CONCLUSIONS: Benzene exposure increases mtDNAcn levels in benzene-exposed workers.

Influence of sex and menopausal status on the relationship between metabolic syndrome and coronary artery calcification: a Chinese community-based cross-sectional study.

OBJECTIVE: To evaluate the association between metabolic syndrome and coronary artery calcification according to different sex and menopausal status. METHODS: This cross-sectional study included 2,704 adults from the Jidong community (Tangshan, China) recruited from July 2013 to August 2014. Adults aged ≥40 years with no cardiovascular disease and with coronary artery calcification score data were included. Metabolic syndrome was defined according to the 2005 International Diabetes Federation standard. Coronary artery calcification score was determined using the Agatston method. The associations between metabolic syndrome and coronary artery calcification prevalence were evaluated using logistic regression. RESULTS: In the multivariable regression analysis, metabolic syndrome was associated with coronary artery calcification (odds ratio: 1.34, 95% confidence interval: 1.04-1.71, P = 0.021). When stratified by sex, metabolic syndrome was positively associated with coronary artery calcification prevalence in female participants (odds ratio: 2.79, 95% confidence interval: 1.96-3.96, P < 0.001), whereas no association was observed in male participants. Furthermore, metabolic syndrome was associated with a higher prevalence of coronary artery calcification (P < 0.001) independent of adjustment for covariates in postmenopausal women than in premenopausal women, and coronary artery calcification prevalence increased with an increase in conditions related to metabolic syndrome. CONCLUSIONS: Our findings indicate that metabolic syndrome in postmenopausal women is associated with a higher prevalence of coronary artery disease than in premenopausal women and men.

PM2.5 disrupts thyroid hormone homeostasis through activation of the hypothalamic-pituitary-thyroid (HPT) axis and induction of hepatic transthyretin in female rats 2.5.

Fine particulate matter (PM2.5), a ubiquitous environmental pollutant, has been indicated to affect thyroid hormone (TH) homeostasis in women, but the detailed mechanism behind this effect remains unclear. The objective of this study was to evaluate the roles of the hypothalamic-pituitary-thyroid (HPT) axis and hepatic transthyretin in the thyroid-disrupting effects of PM2.5. Sprague Dawley rats were treated with PM2.5 (0, 15 and 30 mg/kg) by passive pulmonary inhalation for 49 days; and recovery experimental group rats were dosed with PM2.5 (30 mg/kg) for 35 days, and no treatment was done during the subsequent 14 days. PM2.5 was handled twice a day by passive pulmonary inhalation throughout the study. After treatment, pathological changes were analyzed by performing haemotoxylin and eosin staining, measuring levels of THs and urine iodine (UI) in serum, plasma, and urine samples using enzyme-linked immunoabsorbent assay, and expression of proteins in the hypothalamus, pituitary, thyroid, and liver tissues of rats were analyzed by immunohistochemistry and Western blotting. The levels of oxidative stress factors, such as reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (Gpx), and nuclear factor-kappa B (NF-κB) in female rats' plasma were also evaluated by ELISA. The results of these analyses revealed that PM2.5 treatment induced pathologic changes in rat thyroid and liver characterized by increased follicular cavity size and decreased amounts of follicular epithelial cells and fat vacuoles, respectively. Serum levels of triiodothyronine, thyroxine, and thyroid stimulating hormone were significantly decreased, plasma NF-κB level was increased and plasma redox state was unbalanced (enhanced ROS, MDA and Gpx levels; reduced SOD activities) in female rats treated with PM2.5 (P < 0.05). PM2.5 treatment suppressed the biosynthesis and biotransformation of THs by increasing sodium iodide symporter, thyroid transcription factor 1, thyroid transcription factor 2, and paired box 8 protein expression levels (P < 0.05). Additionally, thyroid stimulating hormone receptor and thyroid peroxidase levels were significantly decreased (P < 0.05). Both thyrotropin releasing hormone receptor and thyroid stimulating hormone beta levels were enhanced (P < 0.05). Moreover, transport of THs was inhibited due to reduced protein expression of hepatic transthyretin upon treatment with PM2.5. In summary, PM2.5 treatment could perturb TH homeostasis by affecting TH biosynthesis, biotransformation, and transport, affecting TH receptor levels, and inducing oxidative stress and inflammatory responses. Activation of the HPT axis and altered hepatic transthyretin levels therefore appear to play a crucial role in PM2.5-induced thyroid dysfunction.

Enhanced visible light photoelectrocatalytic degradation of tetracycline hydrochloride by I and P co-doped TiO2 photoelectrode.

Elimination of antibiotics such as tetracycline hydrochloride (TC) from wastewater is of great significance, but still faces challenges. Herein, for the first time, I and P co-doped TiO2 catalysts were prepared via a hydrolysis method. We also reported a simple method to prepare I and P co-doped TiO2 photoelectrodes, which exhibited preeminent photoelectrocatalytic (PEC) performance for the decomposition of TC. The synergistic effect of I and P co-doping could significantly improve the charge separation rate and enhance the light absorption capacity of TiO2, leading to an enhancement of PEC activity. The main factors affecting the PEC performance were investigated, and the highest degradation rate constant (4.20 × 10-2 min-1) was achieved when the doping content of P was 4 at% (ITP-4 photoelectrode) at pH 11.02 under visible light. The Langmuir-Hinshelwood kinetic model and active species trapping experiments were selected to investigate the degradation mechanism of TC. The results suggest that the hydroxyl radicals and photogenerated holes were the main active species that were responsible for the decomposition of TC. Moreover, the degradation pathways of TC based on the intermediates also demonstrated that the hydroxyl radicals and holes showed a principal role in degrading TC.

Aberrant resting-state cerebral blood flow and its connectivity in primary dysmenorrhea on arterial spin labeling MRI.

PURPOSE: This study aimed to clarify the resting-state cerebral blood flow alteration patterns induced by primary dysmenorrhea, investigate the relationships between cerebral blood flow alterations and clinical parameters of patients with primary dysmenorrhea, and explore whether brain regions with abnormal cerebral blood flow also feature functional connectivity changes. METHODS: Arterial spin labeling imaging and clinical parameters were acquired in 42 patients with primary dysmenorrhea and 41 healthy controls during their menstrual phases. Differences in cerebral blood flow were compared between the two groups, and the clusters with significant group differences were selected as the regions of interest for further statistical analyses. RESULTS: Compared to healthy controls, patients with primary dysmenorrhea exhibited increased cerebral blood flow in the bilateral precuneus, left posterior cingulate cortex, and right rolandic operculum. Among patients with primary dysmenorrhea, we identified a negative correlation between the cerebral blood flow in the right rolandic operculum and the visual analogue score for anxiety, and greater correlation between the functional connectivity in the precuneus/posterior cingulate cortex and the right middle cingulate cortex, and between the right rolandic operculum and the left inferior parietal lobule and the bilateral postcentral gyrus. DISCUSSION: Cerebral blood flow abnormalities associated with primary dysmenorrhea were mainly concentrated in the areas comprising the default mode network in primary dysmenorrhea patients, which could be involved in the central mechanism of primary dysmenorrhea. Cerebral blood flow alteration in the rolandic operculum may underlie an anxiety-induced compulsive tendency in patients with primary dysmenorrhea. Investigating the enhanced connectivity among various pain-related brain regions could improve understanding of the onset and development of primary dysmenorrhea.

Promoter hypermethylation in CSF3R induces peripheral neutrophil reduction in benzene-exposure poisoning.

Benzene is a global pollutant and has been established to cause leukemia. To better understand the role of DNA methylation in benzene toxicity, peripheral blood mononuclear cells were collected from six benzene-poisoning patients and six matched controls for genome-wide DNA methylation screening by Illumina Infinium Methylation 450 BeadChip. The Gene Chip Human Gene 2.0 ST Array (Affymetrix) was used to analyze global mRNA expression. Compared with the corresponding sites of controls, 442 sites in patients were hypermethylated, corresponding to 253 genes, and 237 sites were hypomethylated, corresponding to 130 genes. The promoter methylation and mRNA expression of CSF3R, CREB5, and F2R were selected for verification by bisulfite sequencing and real-time PCR in a larger data set with 21 cases and 23 controls. The results indicated that promoter methylation of CSF3R (p = .005) and F2R (p = .015) was significantly higher in cases than in controls. Correlation analysis showed that the promoter methylation of CSF3R (p < .001) and F2R (p < .001) was highly correlated with its mRNA expression. In the poisoning cases, neutrophil percentage was significantly different among the high, middle, and low CSF3R-methylation groups (p = .002). In particular, the neutrophil percentage in the high CSF3R-methylation group (48.10 ± 9.63%) was significantly lower than that in the low CSF3R-methylation group (59.30 ± 6.26%) (p = .012). The correlation coefficient between promoter methylation in CSF3R and the neutrophil percentage was -0.445 (p = .020) in cases and - 0.398 (p = .060) in controls. These results imply that hypermethylation occurs in the CSF3R promoter due to benzene exposure and is significantly associated with a reduction in neutrophils.

Electrical Tuning of the SERS Enhancement by Precise Defect Density Control.

Surface-enhanced Raman scattering (SERS) has been widely established as a powerful analytical technique in molecular fingerprint recognition. Although conventional noble metal-based SERS substrates show admirable enhancement of the Raman signals, challenges on reproducibility, biocompatibility, and costs limit their implementations as the preferred analysis platforms. Recently, researches on SERS substrates have found that some innovatively prepared metal oxides/chalcogenides could produce noble metal comparable SERS enhancement, which profoundly expanded the material selection. Nevertheless, to tune the SERS enhancement of these materials, careful experimental designs and sophisticated processes were needed. Here, an electrically tunable SERS substrate based on tungsten oxides (WO3-x) is demonstrated. An electric field is used to introduce the defects in the oxide on an individual substrate, readily invoking the SERS detection capability, and further tuning the enhancement factor is achieved through electrical programming of the oxide leakage level. Additionally, by virtue of in situ tuning the defect density and enhancement factor, the substrate can adapt to different molecular concentrations, potentially improving the detection range. These results not only help build a better understanding of the chemical mechanism but also open an avenue for engaging non-noble metal materials as multifunctional SERS substrates.

A multi-GPU accelerated virtual-reality interaction simulation framework.

In this paper, we put forward a real-time multiple GPUs (multi-GPU) accelerated virtual-reality interaction simulation framework where the reconstructed objects from camera images interact with virtual deformable objects. Firstly, based on an extended voxel-based visual hull (VbVH) algorithm, we design an image-based 3D reconstruction platform for real objects. Then, an improved hybrid deformation model, which couples the geometry constrained fast lattice shape matching method (FLSM) and total Lagrangian explicit dynamics (TLED) algorithm, is proposed to achieve efficient and stable simulation of the virtual objects' elastic deformations. Finally, one-way virtual-reality interactions including soft tissues' virtual cutting with bleeding effects are successfully simulated. Moreover, with the purpose of significantly improving the computational efficiency of each time step, we propose an entire multi-GPU implementation method of the framework using compute unified device architecture (CUDA). The experiment results demonstrate that our multi-GPU accelerated virtual-reality interaction framework achieves real-time performance under the moderate calculation scale, which is a new effective 3D interaction technique for virtual reality applications.

Nicotine Induces Cardiomyocyte Hypertrophy Through TRPC3-Mediated Ca2+/NFAT Signalling Pathway.

BACKGROUND: Nicotine is thought to be an important risk factor for the development of cardiovascular diseases. However, the effects of nicotine on cardiomyocyte hypertrophy are poorly understood. The present study was designed to explore the role of nicotine in cardiomyocyte hypertrophy and its underlying mechanism. METHODS: We used primary cardiomyocytes isolated from Wistar rats to examine the effects of nicotine on intracellular Ca2+ mobilization and hypertrophy determined by immunofluorescence, quantitative polymerase chain reaction, and western blot analysis. A luciferase reporter assay was used to examine the activity of NFAT signalling. RESULTS: We found that nicotine caused cardiomyocyte hypertrophy, which was accompanied by increased intracellular Ca2+. Nicotine-enhanced intracellular Ca2+ concentration ([Ca2+]i) was significantly abolished by store-operated Ca2+ entry (SOCE) and TRPC inhibitors. Knockdown of TRPC3 significantly decreased nicotine-induced SOCE and hypertrophy. Moreover, calcineurin-nuclear factor of activated T cells (NFAT) is involved in TRPC3-mediated Ca2+ signalling and cardiomyocyte hypertrophy. Notably, upregulation of TRPC3 by nicotine requires TRPC3-mediated Ca2+ influx and calcineurin-NFAT signalling activation. CONCLUSIONS: Our findings demonstrate that the prohypertrophic effect of nicotine on cardiomyocytes is dependent on enhanced TRPC3 expression through a calcium-dependent regulatory loop, which could become a potential target for prevention and treatment of cardiac hypertrophy.