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1.
EBioMedicine ; 51: 102583, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31901866

RESUMO

BACKGROUND: Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is an important RNA-binding protein that affects the RNA processing, splicing, transport and stability of many genes. hnRNPA2/B1 is expressed during proliferation and metastasis of various cancer types and promotes such processes. However, the precise role and mechanism of hnRNPA2/B1 in breast cancer remain unclear. METHODS: The association of hnRNPA2/B1 with breast cancer metastasis was assessed using tissue chips, mouse models and publicly available data. The role and mechanism of hnRNPA2/B1 in breast cancer metastasis were studied in cell lines and mouse models. FINDINGS: In contrast to other cancer research findings, hnRNPA2/B1 expression was negatively correlated with breast cancer metastasis. hnRNPA2/B1 inhibited MDA-MB-231 triple-negative breast cancer (TNBC) cell metastasis in vitro and in vivo. hnRNPA2/B1 knockout activated ERK-MAPK/Twist and GR-beta/TCF4 pathways but inhibited STAT3 and WNT/TCF4 signalling pathways. Profilin 2 (PFN2) promoted breast cancer cell migration and invasion, whereas hnRNPA2/B1 bound directly to the UAGGG locus in the 3'-untranslated region of PFN2 mRNA and reduced the stability of PFN2 mRNA. INTERPRETATION: Our data supported the role of hnRNPA2/B1 in tumour metastasis risk and survival prediction in patients with breast cancer. The inhibitory role of hnRNPA2/B1 in metastasis was a balance of downstream multiple genes and signalling pathways. PFN2 downregulation by hnRNPA2/B1 might partly explain the inhibitory mechanism of hnRNPA2/B1 in breast cancer metastasis. Therefore, hnRNPA2/B1 might be used as a new prognostic biomarker and valuable molecular target for breast cancer treatments.

2.
Toxicol Appl Pharmacol ; : 114881, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31954762

RESUMO

BACKGROUND/AIMS: Ethanol (EtOH) exposure during a period comparable to the third trimester in human results in obvious neurotoxicity in the developing hippocampus and persistent deficits in hippocampal neurogenesis. Dexmedetomidine (DEX), a highly selective α-2-adrenergic agonist has been demonstrated to restore the impaired neurogenesis and neuronal plasticity in the dentate gyrus (DG) that follows neurological insult. However, the protective roles of DEX in the EtOH-induced deficits of postnatal neurogenesis in the hippocampus are still unknown. METHODS: Mice were pretreated with DEX prior to EtOH exposure to determine its protective effects on impaired postnatal hippocampal neurogenesis. Six-day-old neonatal mice were treated with DEX (125 µg/kg) or saline, followed by EtOH at a total of 5 g/kg or an equivalent volume of saline on P7. Immunohistochemistry and immunofluorescence were used to evaluate the neurogenesis and activated microglia in the DG. Quantitative real time PCR (qRT-PCR) was utilized to assess the expression of inflammatory factors in the hippocampus. RESULTS: DEX pretreatment attenuated the inhibition of EtOH-mediated hippocampal neurogenesis and the reduction of hippocampal neural precursor cells (NPCs). We further confirmed that DEX pretreatment reversed the EtOH-induced microglia activation in the DG as well as the upregulation of the hippocampal TNFα, MCP-1, IL-6, and IL-1ß mRNA levels. CONCLUSION: Our findings indicate that DEX pretreatment protects against EtOH-mediated inhibition of hippocampal neurogenesis in postnatal mice and reverses EtOH-induced neuroinflammation via repressing microglia activation and the expression of inflammatory cytokines.

3.
J Hazard Mater ; 388: 122032, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31955024

RESUMO

Antibiotics are widely used in livestock and poultry industries, which results in large quantities of antibiotic residues in manure that influences subsequent treatments. In this study, an Escherichia coli strain was engineered to display erythromycin esterase on its cell surface. The engineered strain (E. coli ereA) efficiently degraded erythromycin by opening the macrocyclic 14-membered lactone ring in solution. Erythromycin (50 mg/L) was completely degraded in a solution by E. coli ereA (1 × 109 CFU/mL) within 24 h. E. coli ereA retained over 86.7 % of the initial enzyme activity after 40 days of storage at 25 °C, and 78.5 % of the initial activity after seven repeated batch reactions in solution at 25 °C. Mice were fed with E. coli ereA and real-time quantitative PCR data showed that E. coli ereA colonized in the mice large intestine. The mice group fed E. coli ereA exhibited 83.13 % decrease in erythromycin levels in their feces compared with the mice group not fed E. coli ereA. E. coli ereA eliminated antibiotics from the source preventing its release into the environment. The surface-engineered strain therefore is an effective alternative agent for treating recalcitrant antibiotics, and has the potential to be applied in livestock and poultry industries.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31909969

RESUMO

Paclitaxel (PTX) is a widely used anticancer drug that works by inhibiting microtubule disassembly. PTX safety was greatly enhanced by embedding it with human albumin. Here, we study the synergistic effects of PTX with photodynamic therapy (PDT) both in vitro and in vivo by constructing photosensitizer-PTX nanotheranostics (PPNTs). PPNTs were fabricated via noncovalent hydrophobic interactions and π-π stacking between an amphipathic photosensitizer and PTX with an average diameter of ∼80 nm, and these showed high stability in biological conditions. In a tumor-bearing mouse model, PPNTs were shown to accumulate at the tumor site based on three-dimensional fluorescence tomographic imaging. Under 680 nm light irradiation, PPNTs exhibited a superior solid tumor ablation effect in a mouse model, with a dose of PTX (0.2 mg/kg) that is 10-fold lower than that typically used. Mechanistically, PPNTs induced a strong apoptotic response in cells under light illumination and showed an increased antitumor efficacy that is 47.2-fold and 57.6-fold higher than that of the photosensitizer nanoparticles (PNTs) and free PTX, respectively. In addition, PPNTs showed enhanced cellular uptake with focused mitochondria and lysosome colocalization compared to that of PNTs and the amount of PTX delivered in PPNTs was sufficient to induce cell cycle arrest in the G2/M phase. These findings indicated that the current combination therapy has advantages over monotherapy in promoting tumor regression and ultimately achieving tumor elimination.

5.
Nucleic Acids Res ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31943080

RESUMO

Allele-specific protospacer adjacent motif (asPAM)-positioning SNPs and CRISPRs are valuable resources for gene therapy of dominant disorders. However, one technical hurdle is to identify the haplotype comprising the disease-causing allele and the distal asPAM SNPs. Here, we describe a novel CRISPR-based method (CRISPR-hapC) for haplotyping. Based on the generation (with a pair of CRISPRs) of extrachromosomal circular DNA in cells, the CRISPR-hapC can map haplotypes from a few hundred bases to over 200 Mb. To streamline and demonstrate the applicability of the CRISPR-hapC and asPAM CRISPR for allele-specific gene editing, we reanalyzed the 1000 human pan-genome and generated a high frequency asPAM SNP and CRISPR database (www.crispratlas.com/knockout) for four CRISPR systems (SaCas9, SpCas9, xCas9 and Cas12a). Using the huntingtin (HTT) CAG expansion and transthyretin (TTR) exon 2 mutation as examples, we showed that the asPAM CRISPRs can specifically discriminate active and dead PAMs for all 23 loci tested. Combination of the CRISPR-hapC and asPAM CRISPRs further demonstrated the capability for achieving highly accurate and haplotype-specific deletion of the HTT CAG expansion allele and TTR exon 2 mutation in human cells. Taken together, our study provides a new approach and an important resource for genome research and allele-specific (haplotype-specific) gene therapy.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31915860

RESUMO

RATIONALE: Deficits in response inhibition associated with heroin use could last several months after abstinence in heroin users, and their response inhibition can also be interfered with task-irrelevant drug-related cues. However, it is unclear whether exposure to drug-related cues affects subsequent response inhibition in heroin users following abstinence. OBJECTIVES: The present study aimed to investigate how drug-related cues with different durations between stimulus presentations, referred to as stimulus onset asynchronies (SOAs), affect subsequent response inhibition in heroin abstainers (HAs) with different length of abstinence. METHODS: Sixty-seven male HAs performed a modified Go/NoGo task in which a motor response to frequent Go targets and no response to rare NoGo targets were required and a Go or NoGo target was displayed after either a heroin-related or a neutral picture presented for the 200 ms and 600 ms SOAs. RESULTS: The HAs responded significantly faster to Go targets following the neutral pictures for the 600 ms SOA compared to other conditions. They also made more commission errors following heroin-related pictures compared to neutral pictures regardless of the SOAs. The shorter-term HAs made more commission errors compared to the longer-term HAs following the 200 ms SOA, and it was only a trend when the SOA was 600 ms. Additionally, negative correlations between the duration of current abstinence and commission errors were observed following cues with the 200 ms SOA. CONCLUSIONS: Impaired response inhibition in HAs can be improved through protracted drug abstinence. However, that effect can be reduced by exposure to drug-related cues, which may increase the risk of relapse.

7.
BMJ Open ; 10(1): e031028, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31924633

RESUMO

OBJECTIVE: The application of bowel movement frequency (BMF) in primary care is limited by the lack of solid evidence about the associations of BMF with health outcomes apart from Parkinson's disease and colorectal cancer. We examined the prospective associations of BMF with major vascular and non-vascular diseases outside the digestive system. DESIGN: Population-based prospective cohort study. SETTING: The China Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008. PARTICIPANTS: 487 198 participants aged 30 to 79 years without cancer, heart disease or stroke at baseline were included and followed up for a median of 10 years. The usual BMF was self-reported once at baseline. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident events of predefined major vascular and non-vascular diseases. RESULTS: In multivariable-adjusted analyses, participants having bowel movements 'more than once a day' had higher risks of ischaemic heart disease (IHD), heart failure, chronic obstructive pulmonary disease, type 2 diabetes mellitus and chronic kidney disease (CKD) when compared with the reference group ('once a day'). The respective HRs (95% CIs) were 1.12 (1.09 to 1.16), 1.33 (1.22 to 1.46), 1.28 (1.22 to 1.36), 1.20 (1.15 to 1.26) and 1.15 (1.07 to 1.24). The lowest BMF ('less than three times a week') was also associated with higher risks of IHD, major coronary events, ischaemic stroke and CKD. The respective HRs were 1.07 (1.02 to 1.12), 1.22 (1.10 to 1.36), 1.11 (1.05 to 1.16) and 1.20 (1.07 to 1.35). CONCLUSION: BMF was associated with future risks of multiple vascular and non-vascular diseases. The integration of BMF assessment and health counselling into primary care should be considered.

8.
PLoS Genet ; 16(1): e1008577, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31929527

RESUMO

Circadian systems provide a fitness advantage to organisms by allowing them to adapt to daily changes of environmental cues, such as light/dark cycles. The molecular mechanism underlying the circadian clock has been well characterized. However, how internal circadian clocks are entrained with regular daily light/dark cycles remains unclear. By collecting and analyzing indirect calorimetry (IC) data from more than 2000 wild-type mice available from the International Mouse Phenotyping Consortium (IMPC), we show that the onset time and peak phase of activity and food intake rhythms are reliable parameters for screening defects of circadian misalignment. We developed a machine learning algorithm to quantify these two parameters in our misalignment screen (SyncScreener) with existing datasets and used it to screen 750 mutant mouse lines from five IMPC phenotyping centres. Mutants of five genes (Slc7a11, Rhbdl1, Spop, Ctc1 and Oxtr) were found to be associated with altered patterns of activity or food intake. By further studying the Slc7a11tm1a/tm1a mice, we confirmed its advanced activity phase phenotype in response to a simulated jetlag and skeleton photoperiod stimuli. Disruption of Slc7a11 affected the intercellular communication in the suprachiasmatic nucleus, suggesting a defect in synchronization of clock neurons. Our study has established a systematic phenotype analysis approach that can be used to uncover the mechanism of circadian entrainment in mice.

9.
AAPS PharmSciTech ; 21(2): 66, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932983

RESUMO

The purpose of this study was to investigate the potential of Bletilla striata polysaccharide (BSP, a natural glucomannan material) for the development of a gastroretentive drug delivery system for the first time. Novel BSP-based porous wafer was prepared for levofloxacin hydrochloride (LFH) delivery by combining floating, swelling, and mucoadhesion mechanisms. The influences of BSP and ethyl cellulose (EC) on drug release and mucoadhesive strength were studied by 32 factorial design. The optimized matrix was coated with polycaprolactone (PCL) electrospun membrane by electrospinning and heat treatment technology. The optimized formula (F6, coated) exhibited Q4 h of 41.20 ± 1.90%, Q8 h of 76.49 ± 1.69%, and mucoadhesive strength of 86.11 ± 1.33 gf, and its drug release profile most closely resembled the Korsmeyer-Peppas model with anomalous diffusion driving mechanism. F6 (coated) also presented excellent buoyancy, preferred swelling characteristic due to the porous structure formed by freeze-drying. Meanwhile, the internal morphology, physical state, drug-excipient compatibility, and thermal behavior were recorded. The negligible cytotoxicity of F6 (coated) was observed in human gastric epithelial cell cultures. In the in vitro antimicrobial experiment, the prepared wafer exhibited obvious bacterial inhibition zone, and due to its longer gastric retention, the wafer also performed a more effective Helicobacter pylori clearance than free LFH in vivo. Graphical abstract.

10.
J Cardiovasc Pharmacol ; 75(1): 45-53, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895879

RESUMO

Atherosclerosis is a chronic inflammation condition resulting from the interaction between lipoproteins, monocyte-derived macrophages, T lymphocytes, and other cellular elements in the arterial wall. Macrophage-derived foam cells play a key role in both early and advanced stage of atherosclerosis. Previous studies have shown that berberine could inhibit foam cell formation and prevent experimental atherosclerosis. However, its underlying molecular mechanisms have not been fully clarified. In this study, we explored the cholesterol-lowering effects of berberine in macrophage-derived foam cells and investigated its possible mechanisms in prevention and treatment of atherosclerosis. Here, we demonstrated that berberine could inhibit atherosclerosis in apolipoprotein E-deficient mice and induce cholesterol reduction as well as decrease the content of macrophages. Berberine can regulate oxLDL uptake and cholesterol efflux, thus suppresses foam cell formation. Mechanisms study showed that berberine can suppress scavenger receptor expression via inhibiting the activity of AP-1 and upregulate ATP-binding cassette transporter via activating Nrf2/HO-1 signaling in human macrophage. In summary, berberine significantly inhibits atherosclerotic disease development by regulating lipid homeostasis and suppressing macrophage foam cell formation.

11.
Hemodial Int ; 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31808994

RESUMO

INTRODUCTION: Hemodialysis catheter-related superior vena cava (SVC) occlusions can cause considerable morbidity for patients and be challenging to treat if refractory to conventional guide wire transversal. This pilot study assessed the feasibility and safety of sharp recanalization of SVC occlusion in hemodialysis patients. METHODS: This study retrospectively enrolled hemodialysis patients treated in West China Hospital diagnosed with SVC occlusion who failed traditional guide wire transversal from January 2014 to November 2017. In brief, a guide wire from the femoral approach was advanced to the lower end of the obstructive lesion to act as a target, while the stiff end of hydrophilic wire was advanced though a jugular approach. Under fluoroscopic guidance in biplane imaging, the occlusive SVC lesion was penetrated with the stiff wire that was snared and pulled through. Graded dilation of the SVC and subsequent tunneled-cuffed catheter implantation were performed. Demographic information and clinical outcomes were recorded and evaluated. FINDINGS: Sixteen patients with a mean age of 62 ± 13 years (13 females and 3 males) who received SVC sharp recanalization were included in this study. The sharp recanalization procedure was successfully performed in 14 patients (87.5%). Two patients were complicated with SVC laceration and hemopericardium but remained asymptomatic and required no surgical repair. One patient suffered ventricular fibrillation during procedure. Despite the return of spontaneous circulation, the patient unfortunately died of gastrointestinal tract bleeding after 3 days in ICU. Follow-up suggested the 6-month catheter patency to be 92.85% and 12-month catheter patency to be 58.33%. No long-term procedure-related complications were recorded. DISCUSSION: Sharp recanalization might be a feasible strategy in managing SVC occlusion in hemodialysis patients. The potential life-threatening complications (cardiac arrhythmia and SVC laceration) necessitate strict eligibility screening, skillful operation, and avoidance of over-dilation of SVC.

12.
Molecules ; 24(24)2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31817084

RESUMO

The use of foodstuff as natural medicines has already been established through studies demonstrating the pharmacological activities that they exhibit. Knowing the nutritional and pharmacological significance of foods enables the understanding of their role against several diseases. Among the foods that can potentially be considered as medicine, is sesame or Sesamum indicum L., which is part of the Pedaliaceae family and is composed of its lignans such as sesamin, sesamol, sesaminol and sesamolin. Its lignans have been widely studied and are known to possess antiaging, anticancer, antidiabetes, anti-inflammatory and antioxidant properties. Modern chronic diseases, which can transform into clinical diseases, are potential targets of these lignans. The prime example of chronic diseases is rheumatic inflammatory diseases, which affect the support structures and the organs of the body and can also develop into malignancies. In line with this, studies emphasizing the anti-inflammatory and anticancer activities of sesame have been discussed in this review.

14.
Chem Commun (Camb) ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790113

RESUMO

The iodofluorination of alkynyl and alkenyl MIDA (N-methyliminodiacetyl) boronates led to the synthesis of two types of fluorinated organoborons bearing a valuable C-I bond. The B(MIDA) moiety confers exclusive regioselectivity to the reaction, and the products were formed in generally good yields. Preliminary utility of the products was demonstrated.

15.
Front Genet ; 10: 1149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803236

RESUMO

Dilated cardiomyopathy (DCM) is an important cause of sudden death and heart failure with an unknown etiology. Recent studies have suggested that long non-coding RNA (lncRNA) can interact with microRNA (miRNA) and indirectly interact with mRNA through competitive endogenous RNA (ceRNA) activities. However, the mechanism of ceRNA in DCM remains unclear. In this study, a miRNA array was first performed using heart samples from DCM patients and healthy controls. For further validation, we conducted real-time quantitative reverse transcription (RT)-PCR using samples from DCM patients and a doxorubicin-induced rodent model of cardiomyopathy, revealing that miR-144-3p and miR-451a were down-regulated, and miR-21-5p was up-regulated. Based on the ceRNA theory, we constructed a global triple network using data from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI-GEO) and our miRNA array. The lncRNA-miRNA-mRNA network comprised 22 lncRNA nodes, 32 mRNA nodes, and 11 miRNA nodes. Hub nodes and the number of relationship pairs were then analyzed, and the results showed that two lncRNAs (NONHSAT001691 and NONHSAT006358) targeting miR-144/451 were highly related to DCM. Then, cluster module and random walk with restart for the ceRNA network were analyzed and identified four lncRNAs (NONHSAT026953/NONHSAT006250/NONHSAT133928/NONHSAT041662) targeting miR-21 that were significantly related to DCM. This study provides a new strategy for research on DCM or other diseases. Furthermore, lncRNA-miRNA pairs may be regarded as candidate diagnostic biomarkers or potential therapeutic targets of DCM.

16.
J Inflamm (Lond) ; 16: 24, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827407

RESUMO

Background: Neuregulin receptor degradation protein-1 (Nrdp1) is an E3 ubiquitin ligase that plays an important role in regulating cell growth, apoptosis and oxidative stress. However, the data regarding its expression and exact mechanism in neuronal injury following ICH has not been well identified. Methods: In this study, primary cortical neurons from C57BL/6 mice were subjected to erythrocyte lysates. Nrdp1 expression, cell apoptosis, caspase-3 and BRUCE levels were detected. In addition, inflammatory response, brain edema, and neurological injury in ICH mice were also assessed. Results: We found that the expression of Nrdp1 was significantly increased in neuron cells accompanied by up-regulation of active caspase-3 and decreased expression of BRUCE (an inhibitor of apoptosis protein). However, inhibiting Nrdp1 levels of neurons reduced caspase-3 activity but induced up-regulation of BRUCE. In vivo, inhibiting Nrdp1 levels increased pro-inflammatory cytokines, brain edema, and neurological injury following ICH. Conclusions: Taken together, the data suggested that Nrdp1 might play a crucial role in neuronal apoptosis via inhibiting BRUCE following ICH.

17.
Front Oncol ; 9: 1294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31828036

RESUMO

p38 mitogen-activated protein kinases are signaling molecules with major involvement in cancer. A detailed mechanistic understanding of how p38 MAPK family members function is urgently warranted for cancer targeted therapy. The conformational dynamics of the most common member of p38 MAPK family, p38α, are crucial for its function but poorly understood. Here we found that, unlike in other cancer types, p38α is significantly activated in pancreatic adenocarcinoma samples, suggesting its potential for anti-pancreatic cancer therapy. Using a state of the art supercomputer, Anton, long-timescale (39 µs) unbiased molecular dynamics simulations of p38α show that apo p38α has high structural flexibility in six regions, and reveal potential catalysis mechanism involving a "butterfly" motion. Moreover, in vitro studies show the low-selectivity of the current p38α inhibitors in both human and mouse pancreatic cancer cell lines, while computational solvent mapping identified 17 novel pockets for drug design. Taken together, our study reveals the conformational dynamics and potentially druggable pockets of p38α, which may potentiate p38α-targeting drug development and benefit pancreatic cancer patients.

18.
Int J Biol Macromol ; 145: 620-633, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31883893

RESUMO

Herbal medicines are frequently used for the prevention and treatment of obesity and obesity-related disorders. Our preliminary screening showed that St. John's Wort (SJW) displayed potent inhibition on pancreatic lipase (PL), a key hydrolase responsible for lipid digestion and absorption in mammals. Herein, the inhibition potentials and inhibitory mechanism of SJW extract and its major constituents on PL were fully investigated by a set of in vitro and in silico studies. The results clearly demonstrated that the naphthodianthrones, biflavones and most of flavonoids in SJW displayed strong to moderate inhibition on PL. Among all tested natural compounds, two naphthodianthrones (hypericin and pseudohypericin) and one biflavone (I3,II8-biapigenin) isolated from SJW exhibited potent PL inhibition activity, with the IC50 values of <1 µM. Inhibition kinetics analyses showed that hypericin, pseudohypericin and I3,II8-biapigenin inhibited PL via a mixed manner, while molecular dynamics simulations revealed that three newly identified PL inhibitors could bind on PL at both the catalytic cavity and the interface between colipase and the C-terminal domain of PL. Collectively, our findings suggested that part of major constituents in SJW displayed potent PL inhibition activities, which could be used as lead compounds for the development of novel PL inhibitors.

19.
Huan Jing Ke Xue ; 40(9): 3868-3874, 2019 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854848

RESUMO

In order to study the seasonal variations in the chemical composition of atmospheric particulate matter with diameters less than 2.5 µm (PM2.5) and its influence on visibility in background areas, atmospheric PM2.5 samples were collected in spring, summer, autumn, and winter 2016 at Qixingtai in Ji'nan. The pollution characteristics of water-soluble ions components, organic carbon (OC), and elemental carbon (EC) were analyzed, and their regional transmission contributions were studied. The results show that NH4+, SO42-, and NO3- were the main components of water-soluble ions, accounting for 90.24% of the annual total ion concentration. The secondary water soluble inorganic ions were polluted severely. NO3-/SO42- presented obvious seasonal variations of high (low) levels in winter (summer). In each season, SO42- and NH4+ existed mainly in the form of (NH4)2SO4. The value of secondary OC (SOC)/OC ranged from 21.17% to 54.21%, indicating the presence of relatively severe secondary organic pollution in this area. The sulfur oxidation ratio (SOR) value in all seasons was greater than 0.1, indicating that the secondary generation of SO42- occurs in all seasons in this region, and the value of nitrogen oxidation ratio (NOR) in all seasons was higher than the SOR value. The secondary transformation of NO2 in the Qixingtai region was stronger than that of SO2. The range of atmospheric extinction coefficient (Bext) was 172.68-320.61 Mm-1, with an annual mean of 256.48 Mm-1. The atmospheric extinction coefficient showed an obvious seasonal trend of the lowest (highest) in summer (winter). The backward airflow trajectory shows that the Qixingtai was affected mainly by the long-distance transmission from Northwest China and the ocean in spring and summer and by local sources in autumn and winter. A comparison of the characteristics of atmospheric PM2.5 pollution in Ji'nan in 2008 revealed that the influence of motor vehicles on the atmospheric environment has been significantly improved.

20.
Menopause ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31876618

RESUMO

OBJECTIVE: Bone loss is accelerated after menopause in women, as is the risk of hip fracture, but little is known about the importance of age at menopause, time since menopause, and total reproductive years for risk of hip fracture. METHODS: Between 2004 and 2008, the China Kadoorie Biobank recruited 125,336 postmenopausal women who had a natural menopause and recorded 1,327 incident cases of hip fracture during the first 10 years of follow-up. Multivariable Cox regression was used to estimate hazard ratios and 95% CIs for incident hip fracture for age at menopause, time since menopause, and total reproductive years. RESULTS: The mean (SD) age at menopause was 48.8 (4.0) years. Compared with women who reached menopause before age 53 years, women with a later age at menopause had a 22% (95% CI, 11%-35%) lower risk of hip fracture. Compared with women who were <5 years since menopause, those who were 5 to 9, 10 to 14, 15 to 19, and ≥20 years since menopause had hazard ratios of hip fracture of 1.43 (95% CI, 1.01-2.04), 2.10 (95% CI, 1.71-2.57), 2.50 (95% CI, 2.21-2.83), and 2.33 (95% CI, 1.97-2.75), respectively. Women with a longer (≥36 y) versus shorter (<30 y) duration of total reproductive years had a 19% (95% CI, 9-28) lower risk of hip fracture. CONCLUSIONS: Women with younger age at menopause, longer interval since menopause, or shorter duration of total reproductive years had the highest risks of hip fracture.

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