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As an energy-intensive industry, cement production can emit significant air pollutants that negatively impact human health and the environment. Geospatial data on cement plants are crucial for managing the cement industry and designing effective policies to mitigate ever-increasing air pollution. However, the available fundamental asset-level datasets of global cement plants are generally incomplete and may not adequately satisfy the above requirements. To address this gap, (i) we proposed an innovative semi-automatic framework, which is based on the high-temperature signal from active kilns in time-series Landsat-8 Operational Land Imager (OLI) and Sentinel-2 Multispectral Instrument (MSI) imagery and the iconic characteristics of cement processing equipment in high-resolution imagery, to identify global cement plants, assess their operational status, and evaluate relevant activity levels. (ii) We compiled a state-of-the-art inventory of global cement plants, enriched with detailed attributes, using multi-source spaceborne observations/products. We identified 3075 cement plants with rotary/shaft kilns and pinpointed 1960 locations for cement grinding and storage facilities. (iii) We investigated the status of global cement plants using time-series Sentinel-2 MSI imagery. Our results show that from 2016 to date, 69.3% of cement plants are continuously operating, 4.3% were newly constructed, and 26.4% were decommissioned. (iv) We proposed two normalized metrics, namely the occurrence rate and the mean detected area, to assess the activity level of cement plants. The results showed that the rotary kilns in wet-process cement plants had the highest activity level due to the higher energy consumption. The activity level of global cement plants increased by ∼9% during 2016–2021 and then decreased by ∼4% in 2022, possibly due to the influence of COVID-19 and weak market demand. The proposed framework provides valuable insights for investigating the locations and dynamics of other industrial hot sources, such as those in steel mills, coke ovens, refineries, and oil/gas development areas, to improve the estimates of CO 2 emissions and air pollutants and then to promote climate action. • An innovative framework for identifying global cement plants was proposed. • The state-of-the-art inventory of global cement plants was compiled. • The operational status was assessed by time-series Sentinel-2 MSI images. • The activity level increased by 8.8% during 2016–2021 and decreased by 4% in 2022. [ABSTRACT FROM AUTHOR]

• Inactivated vaccines appear to be safe for PWE following resection surgery. • Individuals with active seizures may have a reduced acceptance of vaccines. • Education and public awareness campaigns focused on promoting vaccine safety in children are required to increase COVID-19 vaccination rates. In light of the ongoing COVID-19 pandemic, vaccination has emerged as the primary and most effective solution. The aim of this study was to examine compliance rates of vaccination and explore the factors that predict vaccine uptake among patients with epilepsy (PWE) who have undergone resection surgery. To examine the variations in vaccination coverage, safety concerns, and factors influencing vaccination hesitancy among PWE who have undergone resection surgery, this study recruited patients with at least one-year follow-up. We utilized questionnaires to gather clinical characteristics and obtain information regarding COVID-19 vaccines. Among the 303 patients included in the study, a majority of 229 (75.58%) achieved a seizure-free outcome (Engel Ia). Of these patients, 178 (58.75%) received at least one dose of COVID-19 vaccine, and the vaccination rate has remained relatively consistent over the past six months. Nearly 94.95% of those who received the vaccine completed the full vaccination regimen, with the majority (n = 174, 97.75%) opting for an inactivated vaccine. Only three patients reported side effects unrelated to epilepsy, and one patient experienced a worsening of typical aura seizures within one month after vaccination. Notably, significant positive associations were observed between COVID-19 vaccine acceptance and adulthood (age 18 years or older) (OR = 1.820, 95% CI = 1.018–3.252, p = 0.043) as well as achieving a seizure-free outcome (OR = 2.823, 95% CI = 1.619–4.921, p < 0.001). Regarding the unvaccinated patients, approximately one-fifth expressed willingness to receive a future COVID-19 vaccine, while the remainder were hesitant (41.60%) or unsure (39.20%) about vaccination. These reservations mainly stemmed from concerns about the potential worsening of seizures and vaccine safety. Inactivated vaccines can be considered safe for individuals with epilepsy who have undergone resection surgery. The likelihood of being vaccinated was found to be comparatively higher among the cohort with seizure-free status or adults. To promote COVID-19 vaccination among children, it is crucial to implement comprehensive education and public awareness campaigns that emphasize the safety of vaccines. These efforts will help encourage widespread acceptance of vaccination and ensure the well-being of individuals with epilepsy. [ABSTRACT FROM AUTHOR]

NF-E2-related factor 2 (Nrf2) has been shown to be protective in atherosclerosis. The loss of Nrf2 in macrophages enhances foam cell formation and promotes early atherogenesis. Tanshindiol C (Tan C) is isolated from the root of Salvia miltiorrhiza Bge., a traditional Chinese medicine that has been used for the treatment of several cardiovascular diseases for many years. This study was aimed to test the potential role of Tan C against macrophage foam cell formation and to explore the underlying mechanism. Firstly, we observed that Tan C markedly suppressed oxidized low-density lipoprotein (oxLDL) induced macrophage foam cell formation. Then, we found that Tan C was an activator of both Nrf2 and Sirtuin 1 (Sirt1) in macrophages. Nrf2 and Sirt1 synergistically activated the transcription of anti-oxidant peroxiredoxin 1 (Prdx1) after Tan C treatment. More important, we demonstrated that silencing of Prdx1 promoted oxLDL-induced macrophage foam cell formation. Prdx1 upregulated adenosine triphosphate-binding cassette (ABC) transporter A1 (ABCA1) expression and decreased intracellular lipid accumulation. Furthermore, Tan C ameliorated oxLDL induced macrophage foam cell formation in a Prdx1-dependent manner. These observations suggest that Tan C protects macrophages from oxLDL induced foam cell formation via activation of Prdx1/ABCA1 signaling and that Prdx1 may be a novel target for therapeutic intervention of atherosclerosis. [ABSTRACT FROM AUTHOR]

Agriculture is the main source of ammonia (NH 3) emissions which result in air pollution and degrade human health. However, the global pattern of NH 3 emissions still remains uncertain, and very few studies report the crop- and animal-specific NH 3 emissions both regionally and globally. Here, we developed an improved long-term (1961–2018) agricultural NH 3 emissions inventory considering the detailed information of crop- and animal-specific sources at 0.5o grids. Global agricultural NH 3 emissions were estimated as 39.2 Tg N yr-1 averaged over 1961–2018, driven by livestock production (58.4%) and cropland (41.6%). Cattle, rice, maize and wheat together explain about 53.4% of total agricultural NH 3 emissions. Agricultural NH 3 emissions increased by 225% from 18.5 Tg N in 1961–60.1 Tg N in 2018 with the increase rate of 2.1% yr-1 (for cropland 3.8% yr-1 and for livestock 1.3% yr-1). Regarding regions, China, India, Brail, Pakistan, United States and European Union accounted for over half of total agricultural NH 3 emissions. The hotspots of agricultural NH 3 emissions have shifted from the United States and European Union in the 1960s to China and India in recent years. Our findings benefit the understanding of agricultural NH 3 dynamics by crops and animals and provide an important reference for the formulation of NH 3 pollution prevention and control policy. [Display omitted] • An improved long-term agricultural NH 3 emissions inventory is developed. • Integrated crop- and animal-specific NH 3 emissions are estimated. • Cattle, rice, maize and wheat are dominated sources of agricultural NH 3 emissions. • Hotspots of agricultural NH 3 emissions shift from United States and European Union to China and India. [ABSTRACT FROM AUTHOR]

BackgroundMethodsResultsConclusionsAs the high-risk stage of diabetes, the role of prediabetes in the development of hepatocellular carcinoma (HCC) remains unclear. To address this knowledge gap, we undertook a meta-analysis to investigate the potential association between the prediabetic stage and HCC.In this study, two independent investigators conducted a comprehensive search for relevant articles published up until May 2023 in several databases, including PubMed, Web of Science, Medline, EMBASE, and Google Scholar. The results were then summarized using STATA 12.0 software.Our analysis included a total of 6 cohort studies involving 1,490,752 participants, as well as 1 case–control study with 220 participants. The research aimed to examine the association between prediabetes and the risk of HCC. Our meta-analysis revealed that prediabetes was significantly associated with an elevated risk of HCC (odds ratio (OR)/relative risk (RR) = 1.25, 95% confidence interval (CI) 1.06 to 1.48, I2 = 57.2%, p = 0.012), using a random-effects model. Moreover, four cohort studies, encompassing 1,362,847 participants, explored the relationship between prediabetes and HCC mortality. The meta-analysis showed that prediabetes was associated with a higher mortality rate of HCC, also utilizing a random-effects model (hazard ratio (HR) = 1.36, 95% CI 1.02 to 1.81, I2 = 55.8%, p = 0.060).Overall, our findings highlight a significant association between prediabetes and an increased risk of HCC and suggest that prediabetes may also contribute to higher mortality rates among HCC patients. [ABSTRACT FROM AUTHOR]

Introduction: The aim was to evaluate the clinical characteristics and prognostic significance of subclinical seizures (SCSs) on scalp video-electroencephalogram (VEEG) monitoring with or without intracranial electroencephalogram (IEEG) monitoring in patients who had epilepsy surgery. Methods: We reviewed 286 epileptic patients who underwent subsequent epilepsy surgery during scalp-VEEG evaluation with or without IEEG monitoring between 2013 and 2020, with a minimum follow-up of 1 year. The prevalence and clinical characteristics of SCSs, as well as their prognostic significance, were analyzed. Results: A total of 286 patients were enrolled for analysis, and 80 patients had IEEG implanted. SCSs were recorded in 9.79% of the patients based on VEEG and 50% based on IEEG. In the VEEG group (n = 286), younger seizure onset (P = 0.004) was associated with the presence of s-SCSs (SCSs detected on scalp VEEG). In the IEEG group (n = 80), temporal lobe epilepsy (P = 0.015) was associated with the presence of i-SCSs (SCSs detected on IEEG). Of 286 patients, 208 (72.73%) were seizure-free in the VEEG group, and 56 0f 80 patients (70%) were seizure-free in the IEEG group through the last follow-up. In the VEEG group, the presence of s-SCSs did not affect seizure outcome; predictors of seizure recurrence were longer epilepsy duration (P = 0.003, OR 1.003, 95% CI 1.001–1.005), history of focal to bilateral tonic–clonic seizure (P = 0.027, OR 1.665, 95% CI 1.060–2.613), nonspecific pathology (P = 0.018, OR 2.184, 95% CI 1.145–4.163), and incomplete resection (P = 0.004, OR 2.705, 95% CI 1.372–5.332). In the IEEG group, i-SCSs were significantly associated with seizure outcome (P = 0.028, OR 0.371, 95% CI 0.153–0.898). Conclusion: The rate of SCSs captured on IEEG monitoring was higher than that on VEEG monitoring during presurgical evaluation. SCSs detected on VEEG monitoring were associated with younger seizure onset. SCSs detected on IEEG monitoring were associated with temporal lobe epilepsy and also predicted surgical outcomes in focal epilepsy. [ABSTRACT FROM AUTHOR]

Aging provokes both morphological and functional changes in cells, which are accompanied by a fundamental shift in gene expression patterns. One of the characteristic alterations associated with senescence in fibroblast cells is the down-regulation of collagen type I genes. In the present study, we investigated the contribution of myocardin-related transcription factor A, or MRTF-A, in this process. In mouse embryonic fibroblast (MEF) cells and human foreskin fibroblast (HFF) cells, senescence, induced by either progressive passage or treatment with hydrogen peroxide (H 2 O 2), led to augmented lysine acetylation of MRTF-A paralleling down-regulation of collagen type I and SIRT1, a lysine deacetylase. SIRT1 interacted with MRTF-A to promote MRTF-A deacetylation. SIRT1 over-expression or activation by selective agonists enhanced trans-activation of the collagen promoters by MRTF-A. On the contrary, SIRT1 depletion or inhibition by specific antagonists suppressed trans-activation of the collagen promoters by MRTF-A. Likewise, mutation of four lysine residues within MRTF-A rendered it more potent in terms of activating the collagen promoters but unresponsive to SIRT1. Importantly, SIRT1 activation in senescent fibroblasts mitigated repression of collagen type I expression whereas SIRT1 inhibition promoted the loss of collagen type I expression prematurely in young fibroblasts. Mechanistically, SIRT1 enhanced the affinity of MRTF-A for the collagen type I promoters. In conclusion, our data unveil a novel mechanism that underscores aging-associated loss of collagen type I in fibroblasts via SIRT1-mediated post-translational modification of MRTF-A. • Senescence-induced repression of collagen type I accompanies augmented MRTF-A acetylation. • SIRT1 interacts with and deacetylates MRTF-A. • SIRT1 enhances the ability of MRTF-A to activate collagen type I transcription. • SIRT1 promotes MRTF-A recruitment to the collagen promoters defying collagen repression. [ABSTRACT FROM AUTHOR]

The peony pod is a component of the cash crop oil peony (Paeonia suffruticosa Andr.), it accounts for more than half of the quality of the peony seed. However, indiscriminate disposal leads to resource waste. In addition, the pollution caused by the overuse of antibiotics and the evolution of resistance have been a conundrum. There is an urgent need to find a pollutant removal method that conforms to the current concept of sustainable development. In this study, the biomass porous carbon (PC N, Fe -0.5) was prepared and modified by one-step synthesis method using the by-product peony pod as carbon precursor, urea as nitrogen source, and steel slag as magnetic material. The utilization of biomass waste solved resources waste caused by the unreasonable disposal of agricultural solid waste. The doped materials were cheap and easy to obtain, and they improved the structure and function of porous carbon. The maximum adsorption capacity of PC N,Fe -0.5 reached 726.4 mg·g−1 with 100 mg·L−1 of tetracycline (TC). The adsorption mechanism was summarized as pore filling, van der Waals force, π-π EDA, surface complexation, hydrogen bonding and chemisorption. A low-budget tetracycline (TC) removal method was explored through the investigation on the adsorption performance and recovery capability of PC N,Fe -0.5, which was also conducive to realizing the recycling of biomass waste and industrial waste. [Display omitted] • Peony pods acted as carbon sources to prepare porous carbon with excellent pore structure. • The carbonization, activation and modification were realized synchronously in one step. • Activator (KHCO 3), urea (N) and steel slag (Fe) were green, low-cost and resource-based. • The maximum adsorption capacity of PC N,Fe -0.5 for tetracycline was 726.4 mg·g−1. [ABSTRACT FROM AUTHOR]

Developing probes for simultaneous diagnosis and killing of cancer cells is crucial, yet challenging. This article presents the design and synthesis of a novel Rhodamine B fluorescence probe. The design strategy involves utilizing an anticancer drug (Melphalan) to bind with a fluorescent group (HRhod-OH), forming HRhod-MeL, which is non-fluorescent. However, when exposed to the high levels of reactive oxygen species (ROS) of cancer cells, HRhod-MeL transforms into a red-emitting Photocage (Rhod-MeL), and selectively accumulates in the mitochondria of cancer cells, where, when activated with green light (556 nm), anti-cancer drugs released. The Photocage improve the efficacy of anti-cancer drugs and enables the precise diagnosis and killing of cancer cells. Therefore, the prepared Photocage can detect cancer cells and release anticancer drugs in situ, which provides a new method for the development of prodrugs. [Display omitted] • High fluorescence quantum yield and good biocompatibility. • Simultaneously detect the release of cancer cells and anticancer drugs. • Targeting, releasing and imaging. [ABSTRACT FROM AUTHOR]

Aims Macrophage-mediated inflammatory response represents a key pathophysiological process in a host of cardiovascular diseases including heart failure. Regardless of aetiology, heart failure is invariably preceded by cardiac hypertrophy. In the present study, we investigated the effect of macrophage-specific deletion of myocardin-related transcription factor A (MRTF-A) on cardiac hypertrophy and the underlying mechanism. Methods and results We report that when subjected to transverse aortic constriction (TAC), macrophage MRTF-A conditional knockout (CKO) mice developed a less severe phenotype of cardiac hypertrophy compared to wild-type (WT) littermates and were partially protected from the loss of heart function. In addition, there was less extensive cardiac fibrosis in the CKO mice than WT mice following the TAC procedure. Further analysis revealed that cardiac inflammation, as assessed by levels of pro-inflammatory cytokines and chemokines, was dampened in CKO mice paralleling reduced infiltration of macrophages in the heart. Mechanistically, MRTF-A deficiency attenuated the expression of integrin beta 2 (ITGB2/CD18) in macrophage thereby disrupting adhesion of macrophages to vascular endothelial cells. MRTF-A was recruited by Sp1 to the ITGB2 promoter and cooperated with Sp1 to activate ITGB2 transcription in macrophages. Administration of a CD18 blocking antibody attenuated TAC-induced cardiac hypertrophy in mice. Interaction between MRTF-A and the histone demethylase KDM3A likely contributed to IGTB2 transcription and consequently adhesion of macrophages to endothelial cells. Conclusions Our data suggest that MRTF-A may regulate macrophage trafficking and contribute to the pathogenesis of cardiac hypertrophy by activating ITGB2 transcription. [ABSTRACT FROM AUTHOR]

Aims Establishment of an inflammatory milieu following elevated leukocyte adhesion to the vascular endothelium, which is mediated by transcriptional activation of cell adhesion molecules (CAMs), contributes to the pathogenesis of chronic hypoxia-induced pulmonary hypertension (HPH). The epigenetic switch that dictates CAM transactivation in response to hypoxia in endothelial cells leading up to HPH is not fully appreciated. Methods and results We report here that brahma-related gene 1 (Brg1) and brahma (Brm), two catalytic components of the mammalian chromatin remodelling complex, were induced in cultured endothelial cells challenged with hypoxia in vitro as well as in pulmonary arteries in an animal model of HPH. Over-expression of Brg1/Brm enhanced, while the depletion of Brg1/Brm attenuated, CAM transactivation and adhesion of leukocytes. Endothelial-specific deletion of Brg1/Brm ameliorated vascular inflammation and HPH in mice. Chromatin immunoprecipitation (ChIP) and re-ChIP assays revealed that hypoxia up-regulated the occupancies of Brg1 and Brm on CAM promoters in a nuclear factor κB (NF-κB) -dependent manner. Finally, Brg1 and Brm activated CAM transcription by altering the chromatin structure surrounding the CAM promoters. Conclusion Our data suggest that Brg1 provides the crucial epigenetic link to hypoxia-induced CAM induction and leukocyte adhesion that engenders endothelial malfunction and pathogenesis of HPH. As such, targeting Brg1 in endothelial cells may yield promising strategies in the intervention and/or prevention of HPH. [ABSTRACT FROM PUBLISHER]

Non-alcoholic steatohepatitis (NASH) is characterized by aberrant lipid metabolism in hepatocytes. We investigated the involvement of a histone H3K9 methyltransferase Suv39h2 in the pathogenesis of NASH. NASH is induced by feeding the mice with a high-fat high-carbohydrate (HFHC) diet or a high-fat choline-deficient amino acid defined (HFD-CDAA) diet. The Suv39h2 f/f mice were crossbred with the Alb -Cre mice to specifically delete Suv39h2 in hepatocytes. Ablation of Suv39h2 in hepatocytes improved insulin sensitivity of the mice fed either the HFHC diet or the CDAA-HFD diet. Importantly, Suv39h2 deletion significantly ameliorated NAFLD as evidenced by reduced lipid accumulation, inflammation, and fibrosis in the liver. RNA-seq uncovered Vanin-1 (Vnn1) as a novel transcriptional target for Suv39h2. Mechanistically, Suv39h2 repressed Vnn1 transcription in hepatocytes exposed to free fatty acids. Consistently, Vanin-1 knockdown normalized lipid accumulation in Suv39h2-null hepatocytes. Importantly, a significant correlation between Suv39h2, Vanin-1, and hepatic triglyceride levels was identified in NASH patients. Our study uncovers a novel mechanism whereby Suv39h2 may contribute to NASH pathogenesis and suggests that targeting the Suv39h2-Vanin-1 axis may yield novel therapeutic solutions against NASH. [ABSTRACT FROM AUTHOR]

Interictal epileptiform discharges (IEDs) often co-occur across spatially-separated cortical regions, forming IED networks. However, the factors prompting IED propagation remain unelucidated. We hypothesized that slow oscillations (SOs) might facilitate IED propagation. Here, the amplitude and phase synchronization of SOs preceding propagating and non-propagating IEDs were compared in 22 patients with focal epilepsy undergoing intracranial electroencephalography (EEG) evaluation. Intracranial channels were categorized into the irritative zone (IZ) and normal zone (NOZ) regarding the presence of IEDs. During wakefulness, we found that pre-IED SOs within the IZ exhibited higher amplitudes for propagating IEDs than non-propagating IEDs (delta band: p = 0.001, theta band: p < 0.001). This increase in SOs was also concurrently observed in the NOZ (delta band: p = 0.04). Similarly, the inter-channel phase synchronization of SOs prior to propagating IEDs was higher than those preceding non-propagating IEDs in the IZ (delta band: p = 0.04). Through sliding window analysis, we observed that SOs preceding propagating IEDs progressively increased in amplitude and phase synchronization, while those preceding non-propagating IEDs remained relatively stable. Significant differences in amplitude occurred approximately 1150 ms before IEDs. During non-rapid eye movement (NREM) sleep, SOs on scalp recordings also showed higher amplitudes before intracranial propagating IEDs than before non-propagating IEDs (delta band: p = 0.006). Furthermore, the analysis of IED density around sleep SOs revealed that only high-amplitude sleep SOs demonstrated correlation with IED propagation. Overall, our study highlights that transient but widely distributed SOs are associated with IED propagation as well as generation in focal epilepsy during sleep and wakefulness, providing new insight into the EEG substrate supporting IED networks. • An increase in slow oscillations (SOs) preceding IEDs was observed in the irritative zone and normal zone. • SOs have higher amplitudes before propagating IEDs than before non-propagating IEDs. • Pre-IED SOs show distinct evolution patterns for propagating IEDs versus non-propagating IEDs. • IEDs can exhibit a longer propagation delay (200–500 ms) than previously believed. • SOs correlate with IED generation and propagation during both sleep and wakefulness. [ABSTRACT FROM AUTHOR]

Background and Aims The incidence of inflammatory bowel disease ( IBD) is increasing in China with urbanization and socioeconomic development. There is however a lack of prospective, population-based epidemiology study on IBD in China. The aim of the study is to define the incidence and clinical characteristics of IBD in a developed region of Guangdong Province in China. Methods A prospective, population-based incidence study was conducted from July 2011 to June 2012 in Zhongshan, Guangdong, China. All newly diagnosed IBD cases in Zhongshan were included. Results In total, 48 new cases of IBD (17 Crohn's disease [ CD]; 31 ulcerative colitis [ UC]) were identified over a 1-year period from July 2011. Age-standardized incidence rates for IBD, UC, and CD were 3.14, 2.05, and 1.09 per 100 000 persons, respectively. The median age of UC was 38, and that of CD was 25. Terminal ileum involvement only ( L1), isolated colonic disease ( L2), and ileocolonic disease ( L3) were reported in 24%, 6%, and 71% of patients with CD, respectively. Twenty-four percent of patients had coexisting upper gastrointestinal disease ( L4). Inflammatory ( B1), stricturing ( B2), and penetrating ( B3) behavior were seen in 65%, 24%, and 12% of CD patients, respectively. Fifty-nine percent of CD and 26% of UC patients had extra-intestinal manifestations. Conclusions This is the first prospective, population-based IBD epidemiological study in a developed region of China. The incidence of IBD is similar to that in Japan and Hong Kong but lower than that in South Korea and Western countries. [ABSTRACT FROM AUTHOR]

Abstract: Decreased expression of collagen by vascular smooth muscle cells (SMCs) within the atherosclerotic plaque contributes to the thinning of the fibrous cap and poses a great threat to plaque rupture. Elucidation of the mechanism underlying repressed collagen type I (COL1A2) gene would potentially provide novel solutions that can prevent rupture-induced complications. We have previously shown that regulatory factor for X-box (RFX5) binds to the COL1A2 transcription start site and represses its transcription. Here we report that SIRT1, an NAD-dependent, class III deacetylase, forms a complex with RFX5. Over-expression of SIRT1 or NAMPT, which synthesizes NAD+ to activate SIRT1, or treatment with the SIRT1 agonist resveratrol decreases RFX5 acetylation and disrupts repression of the COL1A2 promoter activity by RFX5. On the contrary, knockdown of SIRT1 or treatment with SIRT1 inhibitors induces RFX5 acetylation and enhances the repression of collagen transcription. SIRT1 antagonizes RFX5 activity by promoting its nuclear expulsion and proteasomal degradation hence dampening its binding to the COL1A2 promoter. The pro-inflammatory cytokine IFN-γ represses COL1A2 transcription by down-regulating SIRT1 expression in SMCs. Therefore, our data have identified as novel pathway whereby SIRT1 maintains collagen synthesis in SMCs by modulating RFX5 activity. [Copyright &y& Elsevier]

Macrophage-dependent inflammation plays a critical role in atherogenesis. Inducible nitric oxide synthase (iNOS) is one of key pro-inflammatory mediators produced in macrophages and its levels can be upregulated by lipopolysaccharide (LPS). The epigenetic mechanism whereby LPS induces iNOS transcription is incompletely understood. We show here myocardin-related transcription factor A (MRTF-A) potentiated iNOS promoter activity in macrophages. There was a decrease in LPS-induced iNOS expression in several cell models due to the lack of MRTF-A. LPS treatment promoted nuclear accumulation of MRTF-A and its interaction with NF-κB/p65 on the iNOS promoter. The absence of MRTF-A prevented the accumulation of active histone marks on the iNOS promoter in response to LPS treatment. Mechanistically, MRTF-A recruited ASH2, a key component of the mammalian histone H3K4 methyltransferase complex, to the iNOS promoter. Silencing of ASH2 attenuated iNOS expression following LPS treatment. Together, our data highlight a role for MRTF-A-dependent recruitment of H3K4 methyltransferase in iNOS induction and as such provide a novel target in the intervention of atherosclerosis. [ABSTRACT FROM AUTHOR]

• The water-soluble Cu2+–CDs has been successfully prepared, and its preparation is simple and low-cost fabrication. • The Cu2+–CDs shows specifically recognize Cr(VI) in any environment by fluorescence quenching without interruptions from other metal ions. • The Cu2+–CDs is highly sensitive to staphylococcus aureus , which is perhaps promising antibiotics. A simple and low-cost fabrication of water-soluble Cu2+-doped carbon dots (Cu2+–CDs) was reported in the paper. The preparation method was mainly via a one-step hydrothermal carbonization of mixture containing cupric acetate monohydrate (Cu(Ac) 2 •H 2 O) and waste tea extract. During pyrolysis process, the waste tea extract underwent simultaneous carbonization and doping of Cu2+ onto carbon dots surfaces. Cu2+–CDs was characterized by FTIR, XRD, TEM, XPS, UV-visible and fluorescence. Cu2+–CDs appeared blue fluorescence under UV-light and the fluorescence could be specifically quenched by Cr(VI). The phenomenon was not disturbed by other metal ions, common anions and amino acids. Cu2+–CDs successfully detected Cr(VI) in real samples (tap water and mineral spring water) by standard adding methods. Besides, Cu2+–CDs was highly sensitive to staphylococcus aureus , and the minimum inhibitory concentration was 0.156 mg/mL. Results showed Cu2+–CDs had outstanding biocompatibility and low cytotoxicity. Therefore, Cu2+–CDs could serve as nanoprobe and potential antibiotics. [ABSTRACT FROM AUTHOR]

Endothelial-derived factors regulate a wide range of pathophysiological events. It has been reported previously that IL-33 promotes acute kidney injury (AKI) in mice although the underlying epigenetic mechanism is unclear. In the present study we investigated the role of BRG1, a chromatin remodeling protein, in AKI with a focus on its regulation of IL-33 expression in endothelial cells. Smarca4 -flox mice were crossbred with Cdh5 -Cre mice to achieve endothelial-specific deletion of BRG1. AKI was induced by unilateral renal ischemia followed by reperfusion. Compared to wild type (WT) littermates, endothelial conditional BRG1 knockout (CKO) mice were protected from ischemia-reperfusion induced AKI as evidenced by decreased plasma creatinine levels, attenuated caste and tubular necrosis, and diminished immune infiltrates. CKO mice also developed less severe renal fibrosis as indicated by expression levels of extracellular matrix proteins, picrosirius red staining of collagenous tissues, and quantification of renal hydroxylproline levels. Of interest, renal expression of IL-33 was down-regulated as result of endothelial BRG1 deficiency. In cultured endothelial cells, BRG1 directly bound to the IL-33 promoter to activate transcription. Endothelial cell-derived conditioned media promoted the synthesis of pro-fibrogenic proteins in renal tubular epithelial cells. Knockdown of either BRG1 or IL-33 in endothelial cells blunted the pro-fibrogenic response in renal tubular epithelial cells. In conclusion, we propose that BRG1 may contribute to ischemia-reperfusion induced renal injury and fibrosis by promoting IL-33 transcription in endothelial cells. • Endothelial BRG1 deletion attenuates renal IR injury in mice. • Endothelial BRG1 deletion attenuates renal fibrosis in mice. • BRG1 activates IL-33 transcription in endothelial cells. • BRG1 regulates renal tubular epithelial cell injury by activating IL-33. [ABSTRACT FROM AUTHOR]

Higher efficient degradation of methyl orange (MO) was demonstrated with nanometer-sized high-silica SAPO-5. By a hydrothermal process, synthesized high-silica SAPO-5 and low-silica SAPO-5 showed Si-to-Al ratios of 4.20 and 0.11, respectively. High-silica SAPO-5 showed much better MO degradation efficiency with a dosage of 70 mg in MO solution with a concentration of 10 mg/L under ultraviolet illumination. High-silica SAPO-5 also exhibited good producibility for preparation and stable photocatalytic activity even after the fifth recycling test. Optical characterizations of DRS, XPS, photocurrent density and time-resolved fluorescence were carried out for SAPO-5 samples. Finally, free radical and hole scavenging experiments were investigated for high-silica SAPO-5, and a MO photodegradation mechanism based on the charge transfer excited state of [Al2+-O−]* was proposed. This work highlights great prospects of high-silica SAPO-5 for organic pollutant removal with virtues of ideal efficiency and environmental friendliness. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Excessive accumulation of reactive oxygen species (ROS), catalyzed by the NADPH oxidases (NOX), is involved in the pathogenesis of ischemia-reperfusion (IR) injury. The underlying epigenetic mechanism remains elusive. Methods: We evaluated the potential role of megakaryocytic leukemia 1 (MKL1), as a bridge linking epigenetic activation of NOX to ROS production and cardiac ischemia-reperfusion injury. Results: Following IR injury, MKL1-deficient (knockout) mice exhibited smaller myocardial infarction along with improved heart function compared with wild-type littermates. Similarly, pharmaceutical inhibition of MKL1 with CCG-1423 also attenuated myocardial infarction and improved heart function in mice. Amelioration of IR injury as a result of MKL1 deletion or inhibition was accompanied by reduced ROS in vivo and in vitro. In response to IR, MKL1 levels were specifically elevated in macrophages, but not in cardiomyocytes, in the heart. Of note, macrophage-specific deletion (MϕcKO), instead of cardiomyocyte-restricted ablation (CMcKO), of MKL1 in mice led to similar improvements of infarct size, heart function, and myocardial ROS generation. Reporter assay and chromatin immunoprecipitation assay revealed that MKL1 directly bound to the promoters of NOX genes to activate NOX transcription. Mechanistically, MKL1 recruited the histone acetyltransferase MOF (male absent on the first) to modify the chromatin structure surrounding the NOX promoters. Knockdown of MOF in macrophages blocked hypoxia/reoxygenation-induced NOX transactivation and ROS accumulation. Of importance, pharmaceutical inhibition of MOF with MG149 significantly downregulated NOX1/NOX4 expression, dampened ROS production, and normalized myocardial function in mice exposed to IR injury. Finally, administration of a specific NOX1/4 inhibitor GKT137831 dampened ROS generation and rescued heart function after IR in mice. Conclusions: Our data delineate an MKL1-MOF-NOX axis in macrophages that contributes to IR injury, and as such we have provided novel therapeutic targets in the treatment of ischemic heart disease. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy is a significant contributor to the global pandemic of heart failure. In the present study we investigated the involvement of myocardin-related transcription factor A (MRTF-A), a transcriptional regulator, in this process. Diabetic cardiomyopathy was induced in mice by feeding with a high-fat diet (HFD) or streptozotocin (STZ) injection. We report that MRTF-A was up-regulated in the hearts of mice with diabetic cardiomyopathy. MRTF-A expression was also up-regulated by treatment with palmitate in cultured cardiomyocytes in vitro. Mechanistically, serum response factor (SRF) bound to the MRTF-A gene promoter and activated MRTF-A transcription in response to pro-diabetic stimuli. Knockdown of SRF abrogated MRTF-A induction in cardiomyocytes treated with palmitate. When cardiomyocytes conditional MRTF-A knockout mice (MRTF-A CKO) and wild type (WT) mice were placed on an HFD to induce diabetic cardiomyopathy, it was found that the CKO mice and the WT mice displayed comparable metabolic parameters including body weight, blood insulin concentration, blood cholesterol concentration, and glucose tolerance. However, both systolic and diastolic cardiac function were exacerbated by MRTF-A deletion in the heart. These data suggest that MRTF-A up-regulation might serve as an important compensatory mechanism to safeguard the deterioration of cardiac function during diabetic cardiomyopathy. [Display omitted] [ABSTRACT FROM AUTHOR]

• Almost two-fifths of patients with adult PWE have received a COVID-19 vaccine. • Attention should be paid to educating epilepsy patients without jobs on the significance and safety of the vaccine. • There was a low risk of seizure worsening in the short term after vaccination in PWE. This study assesses the hesitancy and safety of vaccination administration for the novel 2019 Coronavirus Disease (COVID-19) among adult people with epilepsy (PWE). We recruited adult PWE who visited the outpatient epilepsy clinic from August 2021 to February 2022. We administered a structured questionnaire and a face-to-face interview regarding demographic factors, epilepsy characteristics, and relevant vaccine issues to all patients. Factors related to receiving a vaccine and epilepsy-related events after vaccination were then analyzed. A total of 501 PWE were surveyed; 288 were unvaccinated and 213 were vaccinated. Patients without jobs (OR: 0.59; 95% CI: 0.37–0.95, p = 0.03) were less likely to receive the vaccine compared to students or those with jobs. Other factors associated with vaccination were a higher number of anti-seizure medications (OR: 0.72; 95% CI: 0.55–0.95, p = 0.02) and a lower pre-vaccine seizure frequency (OR: 2.21; 95% CI: 1.06–4.59, p = 0.03). Of the 213 vaccinated patients, 10 (4.70%) reported at least one local and/or systemic side effect. Most patients (92.50%) did not report worse seizures within one month of vaccination. Poor ASM adherence (OR: 15.06; 95% CI: 1.75–129.87, p = 0.01) and fatigue/stimulant drinks such as caffeine (OR: 50.59; 95% CI: 7.57–337.94, p < 0.01) were significantly associated with seizure worsening within one month of receiving the COVID-19 vaccination. Almost two-fifths of patients with adult PWE have received a COVID-19 vaccine. Attention should be paid to educating epilepsy patients without jobs on the significance and safety of the vaccine. There was a low risk of seizure worsening in the short term after vaccination in PWE. [ABSTRACT FROM AUTHOR]

Angiotensin II (Ang II) stimulates endothelin (ET-1) transcription, which contributes to cardiac hypertrophy and fibrosis. We have previously reported that myocardin related transcription factor A (MRTF-A) is indispensable for ET-1 transcription in vascular endothelial cells under hypoxic conditions, indicating that MRTF-A might mediate Ang II-induced pathological hypertrophy. Here we report that Ang II augmented the expression of MRTF-A in cultured endothelial cells and in the lungs of mice with cardiac hypertrophy. Over-expression of MRTF-A enhanced, whereas depletion of MRTF-A attenuated, transcriptional activation of ET-1 gene by Ang II. MRTF-A deficiency ameliorated Ang II induced cardiac hypertrophy and fibrosis in mice paralleling diminished synthesis and release of ET-1. Mechanistically, MRTF-A was recruited to the ET-1 promoter by c-Jun/c-Fos (AP-1) in response to Ang II treatment. Once bound, MRTF-A altered the chromatin structure by modulating histone acetylation and H3K4 methylation on the ET-1 promoter. More importantly, mice with endothelial-specific MRTF-A silencing by lentiviral particles phenocopied mice with systemic MRTF-A deletion in terms of Ang II-induced pathological hypertrophy. In conclusion, we data have unveiled a MRTF-A-containing complex that links ET-1 transactivation in endothelial cells to cardiac hypertrophy and fibrosis by Ang II. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) and acute lung injury (ALI) are considered two severe public health issues, attributed to malfunctions of neutrophils. They can cause chronic inflammation and have association with subsequent tissue damages. There have been rare drugs applying to the efficient treatment in clinical practice. Existing research revealed that Leukotriene B 4 (LTB 4) is the critical endogenous molecule to induce neutrophil inflammatory response. LTB 4 blocking biosynthesis is the potential strategy treating IPF and ALI. In the present study, 45 hydroxamic acid derivatives were produced, and compound 26 was screened out as a highly selective Lead compound of Leukotriene A4 Hydrolase (LTA 4 H), i.e., an enzyme critical to the biosynthesis of LTB 4. This compound is capable of relieving neutrophilic inflammation in an IPF mouse model at early stage, as well as mitigating LPS-induced acute lung injury via a mechanism of LTB 4 blocking biosynthesis in vivo. Whether this compound acts as the potential lead compound for the treatment of IPF and ALI requires further verification. Image 1 • Compound 26 is a highly selective inhibitor of LTA 4 H. • IC 50 of Hydrolase is 99 nM, 2000 fold stronger than IC 50 of Aminopeptidase. • Remarkably alleviates IPF & ALI in vivo. [ABSTRACT FROM AUTHOR]

Ammonia (NH 3), as an alkaline gas, contributes substantially to atmospheric nitrogen deposition, which can cause biodiversity loss, water eutrophication and soil acidification. Advances in the application of satellite observations allow us to gain deeper insights into atmospheric NH 3 concentrations at large spatial scales. A new satellite-based methodology is proposed for estimating dry NH 3 deposition with consideration of bi-directional NH 3 exchange. We estimate the global dry NH 3 deposition for nine years (2008–2016) by using the Infrared Atmospheric Sounding Interferometer Instrument (IASI) NH 3 retrievals. Satellite-based dry NH 3 deposition is in general consistent with measured dry NH 3 deposition over the monitoring sites (R2 = 0.65). Global dry NH 3 deposition over 8 kg N ha−1 is mainly distributed in the Eastern China, Northern and Central Pakistan, and Northern India. An annual increase rate of 0.27 and 0.13 kg N ha−1 y−1 in dry NH 3 deposition during 2008–2016 occurs in Eastern China and Sichuan Basin, which are the major Chinese agricultural regions. The NH 3 compensation point is high during warm months, and can be above 1 μg m−3 such as in Eastern China, implying the importance of considering the NH 3 compensation points for estimating dry NH 3 deposition. We find, if the upward NH 3 flux was ignored, it will cause 11%, 17%, 5% and 3% overestimation in dry NH 3 deposition in Eastern China, Northern India, Eastern United States and Western Europe, respectively. This study presents the potential of using the satellite retrievals to estimate the large-scale dry NH 3 deposition, and the methodology is able to provide temporally continuous and spatially complete fine-resolution datasets. Unlabelled Image • A new satellite-based method is proposed to estimate dry ammonia deposition. • An overestimation in dry ammonia deposition will be caused using unidirectional methods. • Satellite-based estimates capture the general variability of dry ammonia deposition. [ABSTRACT FROM AUTHOR]