Adrenergic microenvironment driven by cancer-associated Schwann cells contributes to chemoresistance in patients with lung cancer.

Doublecortin (DCX)-positive neural progenitor-like cells are purported components of the cancer microenvironment. The number of DCX-positive cells in tissues reportedly correlates with cancer progression; however, little is known about the mechanism by which these cells affect cancer progression. Here we demonstrated that DCX-positive cells, which are found in all major histological subtypes of lung cancer, are cancer-associated Schwann cells (CAS) and contribute to the chemoresistance of lung cancer cells by establishing an adrenergic microenvironment. Mechanistically, the activation of the Hippo transducer YAP/TAZ was involved in the acquisition of new traits of CAS and DCX positivity. We further revealed that CAS express catecholamine-synthesizing enzymes and synthesize adrenaline, which potentiates the chemoresistance of lung cancer cells through the activation of YAP/TAZ. Our findings shed light on CAS, which drive the formation of an adrenergic microenvironment by the reciprocal regulation of YAP/TAZ in lung cancer tissues.

HCR-Assisted RTF-EXPAR-Based Lateral Flow Analysis for Sensitive Detection of H1N1 Influenza Virus.

The H1N1 influenza virus is a significant pathogen responsible for seasonal influenza, and its frequent outbreaks pose substantial challenges to global public health. The present study successfully developed a lateral flow analysis platform that integrates reverse transcription-free exponential amplification reaction (RTF-EXPAR) and hybridization chain reaction (HCR) processes with functionalized quantum dots for the direct detection of H1N1 influenza virus RNA, eliminating the need for reverse transcription. The fluorescence signal on the band recorded with a smartphone can be utilized for the quantitative determination of the target. Interestingly, the dual signal amplification strategy exhibits high sensitivity with a remarkably low detection limit of 10 aM. Moreover, this platform exhibits excellent flexibility and universality, where the various pathogens can be determined by replacing the specific nucleic acid fragments in RTF-EXPAR. The aforementioned advantages reveal its huge potential in the early diagnosis of H1N1 influenza virus infection and developing point-of-care testing (POCT) equipment for nucleic acid analysis.

Effects of Cuisine-Based Chinese Heart-Healthy Diet in Lowering Blood Pressure Among Adults in China: Multicenter, Single-Blind, Randomized, Parallel Controlled Feeding Trial.

BACKGROUND: More than one-fifth of the world's population consumes Chinese cuisines regularly, but no evidence-based healthy diets fitting the Chinese food culture are available for implementation. METHODS: A multicenter, patient- and outcome assessor-blind, randomized feeding trial was conducted among 265 participants with 130 to 159 mm Hg baseline systolic blood pressure (SBP) for 4 major Chinese cuisines (Shangdong, Huaiyang, Cantonese, Szechuan). After a 7-day run-in period on a control diet matching the usual local diets, participants were randomized to continue with the control diet or the cuisine-based Chinese heart-healthy diet for another 28 days. The primary outcome was SBP, and secondary outcomes included diastolic blood pressure and food preference score. Linear regression models were used to estimate the intervention effects and adjustments for the center. The incremental cost per 1 mm Hg reduction in SBP was also calculated. RESULTS: A total of 265 participants were randomized (135 on the Chinese heart-healthy diet and 130 on the control diet), with 52% women, mean age of 56.5±9.8 years, and mean SBP and diastolic blood pressure of 139.4±8.3 and 88.1±8.0 mm Hg, respectively, at baseline. The change in SBP and diastolic blood pressure from baseline to the end of the study in the control group was -5.0 (95% CI, -6.5 to -3.5) mm Hg and -2.8 (95% CI, -3.7 to -1.9) mm Hg, respectively. The net difference of change between the 2 groups in SBP and diastolic blood pressure were -10.0 (95% CI, -12.1 to -7.9) mm Hg and -3.8 (95% CI, -5.0 to -2.5) mm Hg, respectively. The effect size did not differ among cuisines (P for interaction=0.173). The mean food preference score was 9.5 (with 10 the best preferred) at baseline, and the net change during intervention was 0.1 (95% CI, -0.1 to 0.2; P=0.558). The incremental cost-effectiveness ratio per 1 mm Hg SBP reduction was CNY 0.4 (USD 0.06) per day. No difference in the number of adverse events was found between the 2 groups (P=0.259), and none of the adverse events was associated with the intervention. CONCLUSIONS: The Chinese heart-healthy diet is effective, palatable, and cost-effective in reducing blood pressure in Chinese adults with high blood pressure, with a clinically significant effect applicable across major Chinese cuisine cultures. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03882645.

Drug repositioning of tranilast to sensitize a cancer therapy by targeting cancer-associated fibroblast.

Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment that mediate resistance of cancer cells to anticancer drugs. Tranilast is an antiallergic drug that suppresses the release of cytokines from various inflammatory cells. In this study, we investigated the inhibitory effect of tranilast on the interactions between non-small cell lung cancer (NSCLC) cells and the CAFs in the tumor microenvironment. Three EGFR-mutant NSCLC cell lines, two KRAS-mutant cell lines, and three CAFs derived from NSCLC patients were used. To mimic the tumor microenvironment, the NSCLC cells were cocultured with the CAFs in vitro, and the molecular profiles and sensitivity to molecular targeted therapy were assessed. Crosstalk between NSCLC cells and CAFs induced multiple biological effects on the NSCLC cells both in vivo and in vitro, including activation of the STAT3 signaling pathway, promotion of xenograft tumor growth, induction of epithelial-mesenchymal transition (EMT), and acquisition of resistance to molecular-targeted therapy, including EGFR-mutant NSCLC cells to osimertinib and of KRAS-mutant NSCLC cells to selumetinib. Treatment with tranilast led to inhibition of IL-6 secretion from the CAFs, which, in turn, resulted in inhibition of CAF-induced phospho-STAT3 upregulation. Tranilast also inhibited CAF-induced EMT in the NSCLC cells. Finally, combined administration of tranilast with molecular-targeted therapy reversed the CAF-mediated resistance of the NSCLC cells to the molecular-targeted drugs, both in vitro and in vivo. Our results showed that combined administration of tranilast with molecular-targeted therapy is a possible new treatment strategy to overcome drug resistance caused by cancer-CAF interaction.

Enhanced Electrochemiluminescence of Graphitic Carbon Nitride by Adjustment of Carbon Vacancy for Supersensitive Detection of MicroRNA.

Herein, a supersensitive biosensor was constructed by using graphitic carbon nitride with a carbon vacancy (VC-g-C3N4) as an efficient electrochemiluminescence (ECL) emitter for detection of microRNA-21 (miRNA-21). Impressively, VC-g-C3N4 could be prepared by formaldehyde (HCHO)-assisted urea ploycondensation, and the concentration of the carbon vacancy could be controlled by adjusting the dosage of HCHO to improve the ECL performance, in which the carbon vacancy could improve the charge carrier transfer to enhance the conductivity and it also could be used as an electron trap to prevent electrode passivation and facilitate the adsorption of coreactant S2O82- to accelerate its reduction. Compared with original g-C3N4, the introduction of carbon vacancies resulted in a significant enhancement of the ECL efficiency of VC-g-C3N4. With the aid of improved cascade strand displacement amplification (IC-SDA), the ECL biosensor realized sensitive detection of miRNA-21 with a low detection limit of 3.34 aM. This successful strategy promoted the development of g-C3N4 in the ECL field to construct the sensitive biosensor for molecular and disease diagnoses.

The recanalization after thrombolysis as surrogate for clinical outcomes in patients with ST-segment elevation acute myocardial infarction: A systematic review and meta-regression analysis of data from randomized controlled trials.

AIMS: Thrombolytic therapy has been known to be effective in reducing clinical outcomes and increasing recanalization rate among patients with ST-segment elevation acute myocardial infarction (STEMI). However, whether post-thrombolysis recanalization could be used as a surrogate for clinical outcomes is unknown. METHODS: We systematically searched PubMed, EMBASE and the Cochrane Library database to identify randomized controlled trials (RCT) that examined effects of thrombolytic agents in STEMI. Recanalization was defined as TIMI grade 2 or 3 flow. The primary outcome was in-hospital all-cause mortality. Secondary outcomes included in-hospital and 30-day recurrent myocardial infarction (re-MI), composite of death and re-MI, major bleeding and all bleeding. Random-effects meta-regression was used for analysis. RESULTS: We identified 111 eligible study arms and 52 eligible comparisons from 58 RCTs involving 16 536 patients. Our analyses showed that among study arms recanalization rate was significantly inversely associated with the incidence of in-hospital all-cause mortality (ß: -0.07, 95% confidence interval [CI]: -0.13 to -0.02), re-MI (ß: -0.09, 95%CI: -0.18 to -0.01) and the composite of death and re-MI (ß: -0.17, 95%CI: -0.28 to -0.05), and positively associated with in-hospital all bleeding but not with major bleeding. Among paired comparisons, the difference in recanalization rate was associated with the corresponding difference in incidence of in-hospital all-cause mortality (ß: -0.15, 95%CI: -0.28 to -0.01) but the relationship was not significant for any other outcome. CONCLUSION: Pooled evidence from RCTs suggest the potential use of recanalization as a surrogate for clinical outcomes in evaluating the efficacy of thrombolysis among patients with STEMI.

Trajectories of depressive symptoms and subsequent cognitive decline in older adults: a pooled analysis of two longitudinal cohorts.

BACKGROUND: the course of depression is variable, but it is unknown how this variability over time affects long-term cognitive decline. OBJECTIVE: to examine the relationship of different trajectories of depressive symptoms on rates of subsequent cognitive decline in older adults. DESIGN: population-based cohort study. SETTING: communities in the USA and England. SUBJECTS: 17,556 older adults from the Health and Retirement Study and the English Longitudinal Study of Ageing. METHODS: depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale, and trajectories were calculated using group-based trajectory modelling. Global cognitive function and three cognitive domains of memory, executive function and temporal orientation were assessed for up to 18 years. RESULTS: five trajectories of depressive symptoms were identified. Compared with the 'non-depressed' trajectory, the 'worsening depressive symptoms' trajectory (pooled ß = -0.016 standard deviation (SD)/year, 95% confidence interval (CI): -0.021 to -0.010), 'persistent depressive symptoms' trajectory (pooled ß = -0.016 SD/year, 95% CI: -0.024 to -0.008), and 'mild depressive symptoms' trajectory (pooled ß = -0.008 SD/year, 95% CI: -0.014 to -0.003) were associated with faster rates of cognitive decline, while no such association was found for the 'improving depressive symptoms' trajectory (pooled ß = 0.001 SD/year, 95% CI: -0.010 to 0.012). CONCLUSIONS: subthreshold depressive symptoms are associated with an increased rate of cognitive decline, while individuals who show improving depressive symptoms do not exhibit accelerated cognitive decline. These findings raise the possibility that maintaining depressive symptoms as low as possible and ignoring the clinical threshold, might mitigate cognitive decline in older adults.

Development and validation of a deep learning algorithm based on fundus photographs for estimating the CAIDE dementia risk score.

BACKGROUND: the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score is a recognised tool for dementia risk stratification. However, its application is limited due to the requirements for multidimensional information and fasting blood draw. Consequently, an effective and non-invasive tool for screening individuals with high dementia risk in large population-based settings is urgently needed. METHODS: a deep learning algorithm based on fundus photographs for estimating the CAIDE dementia risk score was developed and internally validated by a medical check-up dataset included 271,864 participants in 19 province-level administrative regions of China, and externally validated based on an independent dataset included 20,690 check-up participants in Beijing. The performance for identifying individuals with high dementia risk (CAIDE dementia risk score ≥ 10 points) was evaluated by area under the receiver operating curve (AUC) with 95% confidence interval (CI). RESULTS: the algorithm achieved an AUC of 0.944 (95% CI: 0.939-0.950) in the internal validation group and 0.926 (95% CI: 0.913-0.939) in the external group, respectively. Besides, the estimated CAIDE dementia risk score derived from the algorithm was significantly associated with both comprehensive cognitive function and specific cognitive domains. CONCLUSIONS: this algorithm trained via fundus photographs could well identify individuals with high dementia risk in a population setting. Therefore, it has the potential to be utilised as a non-invasive and more expedient method for dementia risk stratification. It might also be adopted in dementia clinical trials, incorporated as inclusion criteria to efficiently select eligible participants.

Synergistic photothermal-photodynamic-chemotherapy toward breast cancer based on a liposome-coated core-shell AuNS@NMOFs nanocomposite encapsulated with gambogic acid.

A multifunctional nanoplatform with core-shell structure was constructed in one-pot for the synergistic photothermal, photodynamic, and chemotherapy against breast cancer. In the presence of gambogic acid (GA) as the heat-shock protein 90 (HSP90) inhibitor and the gold nanostars (AuNS) as the photothermal reagent, the assembly of Zr4+ with tetrakis (4-carboxyphenyl) porphyrin (TCPP) gave rise to the nanocomposite AuNS@ZrTCPP-GA (AZG), which in turn, further coated with PEGylated liposome (LP) to enhance the stability and biocompatibility, and consequently the antitumor effect of the particle. Upon cellular uptake, the nanoscale metal - organic framework (NMOF) of ZrTCPP in the resulted AuNS@ZrTCPP-GA@LP (AZGL) could be slowly degraded in the weak acidic tumor microenvironment to release AuNS, Zr4+, TCPP, and GA to exert the synergistic treatment of tumors via the combination of AuNS-mediated mild photothermal therapy (PTT) and TCPP-mediated photodynamic therapy (PDT). The introduction of GA serves to reduce the thermal resistance of the cell to re-sensitize PTT and the constructed nanoplatform demonstrated remarkable anti-tumor activity in vitro and in vivo. Our work highlights a facile strategy to prepare a pH-dissociable nanoplatform for the effective synergistic treatment of breast cancer.

Gene Expression Profiling between Patient Groups with High and Low Ki67 Levels after Short-term Preoperative Aromatase Inhibitor Treatment for Breast Cancer.

According to a recent report, a low Ki67 level after short-term preoperative hormone therapy (post-Ki67) might suggest a more favorable prognosis compared with a high post-Ki67 level in patients with hormone receptorpositive/human epidermal growth factor 2-negative (HR+/HER2-) breast cancer with high levels of Ki67. This study aimed to evaluate the pre-treatment genetic differences between these two patient groups. Forty-five luminal B-like patients were stratified into two groups, namely, a group with high (H→H) and one with low (H→L) Ki67 levels after short-term preoperative aromatase inhibitor (AI) treatment. We compared pre-treatment gene expression profiles between the two groups. In gene level analysis, there was no significant difference between the two groups by the class comparison test. In pathway analysis, five metabolism-related gene sets were significantly upregulated in the H→L group (p≤0.05). In the search for novel targets, five genes (PARP, BRCA2, FLT4, CDK6, and PDCD1LG2) showed significantly higher expression in the H→H group (p≤0.05). Several metabolism-related pathways were associated with sensitivity to AI. In the future, it will be necessary to seek out new therapeutic strategies for the poor prognostic group with high post-Ki67.

The hospital management practices in Chinese county hospitals and its association with quality of care, efficiency and finance.

BACKGROUND: County hospitals as the backbone of the China's healthcare system are providing services for over 70% of the total population. However, the hospital management practice (HMP) and its links with quality of care, efficiency and finance in these hospitals are unknown. METHODS: We did two cross-sectional surveys of HMP in 2013 and 2015 among 101 county hospitals across rural China. Three managing roles (hospital director, director of medical affairs office and director of cardiology) and a cardiologist were invited to the surveys. A novel HMP rating scale, with 100 as full score, was used to measure the HMP in 17 indicators under four dimensions (target, operation, performance, and talent management) for each hospital. We analyzed the association of HMP score with variables on quality of care, efficiency and finance using linear mixed models with and without adjustment for potential confounders. FINDINGS: A total of 95 hospitals participated in at least one survey and were included in the analysis. The overall mean HMP score varied dramatically across the hospitals and 84% of them scored less than 60. The dimension mean HMP score was 38.6 (target), 56.4 (operation), 53.2 (performance) and 55.7 (talent), respectively. The pattern of indicator mean HMP score, however, was almost identical between hospitals with high and low overall HMP score, showing the same 'strength' (staff satisfaction, staff performance appraisal, 'hard wares', patient-centered services, etc.) and 'weakness' (target balance, target setting, continuous quality improvement, penalties on staff with dissatisfied performance, etc.). The associations of overall mean HMP score with quality of care and efficiency variables and cost per hospitalization was not statistically significant. The statistical significance in the association with hospital annual total income disappeared after adjusting for region, teaching status, number of competitors, number of staff and number of beds in use. CONCLUSION: The HMP in Chinese county hospitals scores low in general and was not significantly associated with hospital care quality, efficiency and finance. The current healthcare reform in China should address the micro level issues in hospital management practices.

YES1 as a Therapeutic Target for HER2-Positive Breast Cancer after Trastuzumab and Trastuzumab-Emtansine (T-DM1) Resistance Development.

Trastuzumab-emtansine (T-DM1) is a therapeutic agent molecularly targeting human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC), and it is especially effective for MBC with resistance to trastuzumab. Although several reports have described T-DM1 resistance, few have examined the mechanism underlying T-DM1 resistance after the development of acquired resistance to trastuzumab. We previously reported that YES1, a member of the Src family, plays an important role in acquired resistance to trastuzumab in HER2-amplified breast cancer cells. We newly established a trastuzumab/T-DM1-dual-resistant cell line and analyzed the resistance mechanisms in this cell line. At first, the T-DM1 effectively inhibited the YES1-amplified trastuzumab-resistant cell line, but resistance to T-DM1 gradually developed. YES1 amplification was further enhanced after acquired resistance to T-DM1 became apparent, and the knockdown of the YES1 or the administration of the Src inhibitor dasatinib restored sensitivity to T-DM1. Our results indicate that YES1 is also strongly associated with T-DM1 resistance after the development of acquired resistance to trastuzumab, and the continuous inhibition of YES1 is important for overcoming resistance to T-DM1.

Identifying the key sludge properties characteristics in Fe2+-activated persulfate conditioning for dewaterability amelioration and engineering implementation.

Fe2+-activated persulfate process has been introduced into sludge conditioning currently, however the key sludge properties characteristics are worthwhile comprehensively considering for the engineering implementation and management. The results indicated that both the optimal dosages of persulfate and Fe2+ were 0.6 mmol/gTS for sludge dewaterability amelioration, and the reduction efficiencies of capillary suction time (CST), specific resistance of filtration (SRF), and water content (Wc) of dewatered sludge cake reached to 90.5%, 97.2%, and 22.4%, respectively. Significantly, the persulfate and Fe2+ exerted distinctive roles in the conditioning process. The increased persulfate could promote the oxidatively disintegrated effect on sludge flocs, rendering the decrease of particle size. With the oxidative decomposition of the negatively charged biopolymers, sludge zeta potential rose gradually. However, Fe2+ contributed to more persulfate activation to generate free radicals, and the produced Fe3+ could further electrically neutralize the broken sludge fragments. The core mechanism of Fe2+-activated persulfate conditioning is "destroying and re-building" of sludge flocs. Noteworthily, EPS protein was oxidatively degraded more preferentially than EPS polysaccharide, and the decrease of the α-helix content of EPS protein was conducive to the enhancement of sludge dewaterability. Furthermore, the hydrophilic functional groups reduced clearly and element chemical states on sludge flocs altered pronouncedly, also the destroyed structure and microchannel facilitated the flowability of water. These findings provide theoretical and technical support for the practical engineering implementation of the Fe2+-activated persulfate conditioning process.

TaCER1-1A is involved in cuticular wax alkane biosynthesis in hexaploid wheat and responds to plant abiotic stresses.

To protect above-ground plant organs from excessive water loss, their surfaces are coated by waxes. The genes involved in wax formation have been investigated in detail in Arabidopsis but scarcely in crop species. Here, we aimed to isolate and characterize a CER1 enzyme responsible for formation of the very long-chain alkanes present in high concentrations especially during late stages of wheat development. On the basis of comparative wax and transcriptome analyses of various wheat organs, we selected TaCER1-1A as a primary candidate and demonstrated that it was located to the endoplasmic reticulum, the subcellular compartment for wax biosynthesis. A wheat nullisomic-tetrasomic substitution line lacking TaCER1-1A had significantly reduced amounts of C33 alkane, whereas rice plants overexpressing TaCER1-1A showed substantial increases of C25 -C33 alkanes relative to wild type control. Similarly, heterologous expression of TaCER1-1A in Arabidopsis wild type and the cer1 mutant resulted in increased levels of unbranched alkanes, iso-branched alkanes and alkenes. Finally, the expression of TaCER1-1A was found activated by abiotic stresses and abscisic acid treatment, resulting in increased production of alkanes in wheat. Taken together, our results demonstrate that TaCER1-1A plays an important role in wheat wax alkane biosynthesis and involved in responding to drought and other environmental stresses.

Composition and function of soil fungal community during the establishment of Quercus acutissima (Carruth.) seedlings in a Cd-contaminated soil.

This study was designed to explore the functions of soil fungal communities in the Cd tolerance of Q. acutissima seedling. Three Cd levels of 15, 30, and 40 mg kg-1 were set up using the soils collected from Q. acutissima forests. The benomyl was applied to inhibit the fungal communities in the soil. Following a 100-day pot cultivation of Q. acutissima seedlings, the plant growth, Cd content, N uptake, and fungal communities were evaluated. The results showed that the root dry weights were significantly reduced after the benomyl addition at the Cd concentrations of 30 and 40 mg kg-1. Root fungi colonization was enhanced under higher Cd concentrations when soil fungi are present (without the benomyl treatment). The fungi associated with root increased the Cd accumulation in the roots while decreased the Cd transfer to the shoot at 40 mg Cd kg-1. The 15N enrichment in root tip was positively correlated with enzyme activities of soil catalase and urease. And the activities of acid phosphatase, catalase, and urease were inhibited at each Cd level. The abundance of the dominant fungal genus differed in their response to Cd contamination. The ectomycorrhizal fungi of Tomentella and Cortinarius were identified under the higher Cd levels (40 mg kg-1). Our results implied Tomentella and Cortinarius could be applied to enhance the capacity of Quercus acutissima in the bioremediation of Cd polluted soil.

Physicochemical and biological characteristics of BMP-2/IGF-1-loaded three-dimensional coaxial electrospun fibrous membranes for bone defect repair.

Coaxial electrospun fibrous membranes show favorable mechanical properties for use in guided bone regeneration (GBR). We used coaxial electrospinning technology to fabricate three-dimensional nanofiber membranes loaded with BMP-2 and IGF-1, and assessed the physicochemical and biological properties of these novel membranes in vitro. We fabricated four experimental groups of BMP-2/IGF-1/BSA-loaded membranes with different flow ratios (shell/core). Membrane characteristics were assessed by scanning and transmission electron microscopy, and laser confocal microscopy. Physicochemical and drug release properties were evaluated based on contact angle, mechanical property testing, X-ray diffraction analysis, and ELISA. The membranes were seeded with bone marrow-derived mesenchymal stem cells (BMMSCs) to estimate their biological properties based on cell viability and alkaline phosphatase (ALP) activity. The four membrane groups presented uniform diameters and core-shell structures. Acceleration of the shell solution flow rate increased the contact angle and mechanical properties of the fibrous membrane, while dual-factor addition did not impact fiber structure. Each drug-loaded membrane showed a gradually increasing release curve, with varying degrees of burst and sustained release. Compared to the other groups, the membranes with a core-shell flow ratio of 1:10 showed better drug-loading capacity and sustained release performance, higher biological properties and good barrier function. Optimal parameters were chosen based on the physical and chemical characteristics and biological properties of the membrane. Our results imply that the BMP-2/IGF-1/BSA-loaded coaxial electrospun fibrous membrane with optimum parameters is a suitable barrier membrane for GBR, and releases multiple factors promoting osteoconduction and osteoinduction.

Characterization of genome-wide H3K27ac profiles reveals a distinct PM2.5-associated histone modification signature.

BACKGROUND: Current studies of environmental health suggest a link between air pollution components, such as particulate matter (PM), and various diseases. However, the specific genes and regulatory mechanisms implicated in PM-induced diseases remain largely unknown. Epigenetic systems such as covalent modification of histones in chromatin may mediate environmental factors in gene regulation. Investigating the relationships between PM exposure and histone modification status may help understand the mechanisms underlying environment-associated health conditions. METHODS: In this study, we obtained genome-wide profiles of H3K27ac (histone 3 lysine 27 acetylation), known to be an active gene regulatory histone modification marker, in blood samples collected from four Chinese individuals exposed to high or low PM2.5 (particles with diameters up to 2.5 µm). RESULTS: The genome-wide chromatin immunoprecipitation sequencing (ChIP-Seq) data indicated a comprehensive differential H3K27ac landscape across the individual genomes, which was associated with high PM2.5. Moreover, a substantial number of these PM2.5-associated differential H3K27ac markers were in genes involved in immune cell activation, potentially linking these epigenetic changes with air pollution-induced immune and inflammatory responses. CONCLUSIONS: Our study provides the first genome-wide characterization of H3K27ac profiles in individuals subjected to different exposure levels of PM2.5. Future systematic investigations of the relationships between air pollutants and histone modifications in large population samples are warranted to elucidate the contributions of histone modifications to environment-associated diseases.

[Comparison of respiratory diseases and symptoms among school-age children in areas with different levels of air pollution].

OBJECTIVE: To compare the differences of children's health in different area, and to confirm if the prevalence of respiratory diseases and symptoms among children are closely associated with the air pollution. METHODS: A cross-sectional study was conducted in an urban area A and a suburban area B with different levels of air pollution in Beijing. Using a cluster sampling method, we recruited 4 564 children from 3 primary schools in urban A and 4 primary schools in suburban B. Respiratory symptoms were investigated using an international standardized questionnaire including characteristics of children, living conditions, respiratory diseases and symptoms and situation of parents. The concentrations of air pollutants for recent five years were obtained from Reports on the Quality of the Beijing Environment. SPSS 16.0 was used to analyze data. RESULTS: The prevalence of cough, persistent cough, phlegm, persistent phlegm, wheeze and asthma in A area were higher than those in B area [(62.2% vs. 59.9%), (6.3% vs. 3.1%), (42.4% vs. 37.4%),(3.6% vs. 2.4%),(13.3% vs. 9.9%)and(9.5% vs. 5.4%)]. Except for cough, cough with cold, cough without cold, the prevalence of respiratory diseases and symptoms in A area were significantly higher than those in B area (P<0.05). Logistic regression analysis showed the prevalence of persistent cough, phlegm without cold, asthma in A area were significantly higher than those in B area (P<0.05). CONCLUSION: Respiratory diseases and symptoms among school-age children were closely associated with the level of air pollution.

Ultrafine carbon black attenuates the antihypertensive effect of captopril in spontaneously hypertensive rats.

Particulate matter (PM) has been associated with increased blood pressure (BP) by affecting renin-angiotensin system (RAS) on a systemic level in spontaneously hypertensive rats (SHR). RAS in SHR is also an important target for the angiotensin converting enzyme (ACE) inhibitors such as captopril. We aimed to determine if ultrafine carbon black (UCB) could affect antihypertensive effect of captopril in SHR. The rats were randomly divided into six groups. Group 1 did not receive intratracheal instillation; group 2 received saline instillation plus captopril administration; groups 3, 4 and 5 received 0.15 mg/kg, 0.45 mg/kg and 1.35 mg/kg UCB per instillation plus captopril administration, respectively; group 6 received 1.35 mg/kg UCB instillation only. Rats in the above groups were intratracheally instilled with saline or UCB once every two days for three times and captopril was administered to group 2-5 after the final UCB treatment, once a day for one week. The BP was measured 24 h after each intratracheal instillation. During captopril administration and 24 h after last captopril administration, we measured BP every two days for four times. Our results showed that UCB at the dose of 1.35 mg/kg induced pulmonary and systemic inflammation in SHR. Captopril reduced BP in rats exposed to 0, 0.15 and 0.45 mg/kg UCB seven and eleven days after the first UCB instillation, and had no effect on BP in rats exposed to 1.35 mg/kg UCB. Captopril also reduced angiotensin II (AngII) in rats exposed to saline. The reduction, however, was attenuated with increasing doses of UCB. We conclude that UCB attenuated the antihypertensive effect of captopril in SHR, and the effect was accompanied by a systemic increase in the concentration of AngII.

[Concentrations of fine particulate matters and ultrafine particles and influenced factors during winter in an area of Beijing].

OBJECTIVE: To study the concentrations of fine particulate matters and ultrafine particles and influenced factors during winter in an area of Beijing. METHODS: Real-time monitoring of particles' mass and number concentrations were conducted in an area of Beijing from February 7(th) to 27(th), 2013. At the same time, the meteorological data were also collected from the Beijing meteorological website. Differences of the particles' mass and number concentrations during different periods were analyzed using Mann-Whitney U test. Meanwhile, the influenced factors were also analyzed. RESULTS: The mean concentrations of fine particulate matters and ultrafine particles were (157.2 ± 142.8) µg/m³ and (25 018 ± 9 309) particles/cm³, respectively. The particles' number and mass concentrations in haze days were 1.27 times and 2.91 times higher than those in non-haze days, respectively. The mass concentrations of fine particulate matters in the self-monitoring site were higher than those in the nearest central monitoring sites, and the hourly-average concentrations of particles were significantly consistent with those at the commuter times. Meanwhile, the setting off of fireworks/firecrackers during the Spring Festival could lead to short-term increases of the particles' number and mass concentrations. When the wind speed was low and the related humidity was high, the concentrations of particulate matters were relatively high, and the mass concentrations of fine particulate matters were lagged about 1-2 d. CONCLUSION: The level of the particulate matters in this area was high. Heavy traffic, setting off of fireworks/firecrackers and meteorological factors may be some of the main factors affecting the concentrations of the particulate matters in this area. Among those factors, the effect of setting off of fireworks/firecrackers didn't last long and the effect of the meteorological factors had a hysteresis effect.