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1.
Chemosphere ; : 134822, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35523292

RESUMO

Chlorpyrifos (CPF) is an extensively used organophosphorus pesticide. Recently, it has attracted increasing attention due to environmental health problems caused by it. Although numerous studies have discovered the dechlorinated photoproduct of CPF, its structure and toxicity remain largely unknown. In this study, we systematically investigated the structure and toxicity of dechlorinated photoproduct of CPF. The CPF degradation experiment was performed, and its products were identified by ultra high performance liquid chromatography-orbitrap fusion tribid mass spectrometer (UHPLC-Orbitrap Fusion TMS). Additionally, bond dissociation energy (BDE) calculations and photoproduct chemical synthesis were employed to determine the structure of dechlorinated photoproduct of CPF. The toxicity of CPF photoproduct was evaluated through the Ecological Structure Activity Relationships (ECOSAR) Class Program, the Toxicity Estimation Software Tool (T.E.S.T.) software, and acute toxicity testing. The results indicated that the dechlorinated photoproduct of CPF was identified as O,O-Diethyl-O-(3,5-dichloro-2-pyridyl) phosphorothioate (Dechloro-CPF), which was produced in large quantity within the first 30 min of photodegradation experiment. The acute and chronic toxicity values of Dechloro-CPF were obviously higher than those for the other two photoproducts. The median lethal dose (LD50) of Dechloro-CPF was 31.6 mg/kg for female mice and 58.4 mg/kg for male mice. This study reveals the photodegradation mechanism of CPF and confirms that Dechloro-CPF was dechlorinated photoproduct of CPF with potential acute toxicity to aquatic species and mammalian (including human). Our findings will contribute to a more comprehensive risk evaluation of CPF in food and the environment.

2.
Environ Res ; 212(Pt C): 113371, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35504339

RESUMO

Involuntary smoking was a major public health problem for women in China. Previous studies mainly focused on secondhand smoke (SHS), which referred to direct exposure to smoke from burning cigarettes. Little evidence existed about the relationship between thirdhand smoke (THS), the residual tobacco smoke remaining in the environment after tobacco had been smoked, and cervical cancer. The China Kadoorie Biobank (CKB) study recruited 0.3 million female participants from 10 areas across China during 2004-2008. After an 11.2-year median follow-up, we documented 1094 cervical cancer cases. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of SHS and THS with cervical cancer incidence, respectively and jointly. Overall, 60.3% reported weekly SHS exposure, and 83.2% had been exposed to THS. Daily SHS exposure and THS exposure at the enrollment were associated with elevated risks of cervical cancer incidence, with adjusted HRs (95% CI) of 1.22 (1.06,1.42) and 1.24 (1.03,1.49), respectively. The longer the exposure duration, the higher the risks (P for trend = 0.006, 0.035, respectively). Compared with those who were neither exposed to SHS nor THS, those exposed to both SHS and THS had the highest risk, with adjusted HRs (95% CI) of 1.29 (1.05,1.58). Area of residence, breastfeeding duration and heating fuel types are potential effect modifiers. Among Chinese females, both SHS and THS were associated with higher risks of cervical cancer incidence, and a dose-response relationship was found between the exposure duration and cervical cancer risk. Our findings reinforce the need for proactive strategies for tobacco control, to protect women health.

3.
BMJ Open ; 12(5): e058353, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534062

RESUMO

OBJECTIVES: To systematically assess the sero-prevalence and associated factors of major infectious pathogens in China, where there are high incidence rates of certain infection-related cancers. DESIGN: Cross-sectional study. SETTING: 10 (5 urban, 5 rural) geographically diverse areas in China. PARTICIPANTS: A subcohort of 2000 participants from the China Kadoorie Biobank. PRIMARY MEASURES: Sero-prevalence of 19 pathogens using a custom-designed multiplex serology panel and associated factors. RESULTS: Of the 19 pathogens investigated, the mean number of sero-positive pathogens was 9.4 (SD 1.7), with 24.4% of participants being sero-positive for >10 pathogens. For individual pathogens, the sero-prevalence varied, being for example, 0.05% for HIV, 6.4% for human papillomavirus (HPV)-16, 53.5% for Helicobacter pylori (H. pylori) and 99.8% for Epstein-Barr virus . The sero-prevalence of human herpesviruses (HHV)-6, HHV-7 and HPV-16 was higher in women than men. Several pathogens showed a decreasing trend in sero-prevalence by birth cohort, including hepatitis B virus (HBV) (51.6% vs 38.7% in those born <1940 vs >1970), HPV-16 (11.4% vs 5.4%), HHV-2 (15.1% vs 8.1%), Chlamydia trachomatis (65.6% vs 28.8%) and Toxoplasma gondii (22.0% vs 9.0%). Across the 10 study areas, sero-prevalence varied twofold to fourfold for HBV (22.5% to 60.7%), HPV-16 (3.4% to 10.9%), H. pylori (16.2% to 71.1%) and C. trachomatis (32.5% to 66.5%). Participants with chronic liver diseases had >7-fold higher sero-positivity for HBV (OR=7.51; 95% CI 2.55 to 22.13). CONCLUSIONS: Among Chinese adults, previous and current infections with certain pathogens were common and varied by area, sex and birth cohort. These infections may contribute to the burden of certain cancers and other non-communicable chronic diseases.


Assuntos
Doenças Transmissíveis , Infecções por Vírus Epstein-Barr , Helicobacter pylori , Adulto , Idoso , Estudos Transversais , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Vírus da Hepatite B , Herpesvirus Humano 4 , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
4.
Elife ; 112022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35503096

RESUMO

Wnt/ß-catenin signaling has been well established as a potent inhibitor of adipogenesis. Here, we identified a population of adipocytes that exhibit persistent activity of Wnt/ß-catenin signaling, as revealed by the Tcf/Lef-GFP reporter allele, in embryonic and adult mouse fat depots, named as Wnt+ adipocytes. We showed that this ß-catenin-mediated signaling activation in these cells is Wnt ligand- and receptor-independent but relies on AKT/mTOR pathway and is essential for cell survival. Such adipocytes are distinct from classical ones in transcriptomic and genomic signatures and can be induced from various sources of mesenchymal stromal cells including human cells. Genetic lineage-tracing and targeted cell ablation studies revealed that these adipocytes convert into beige adipocytes directly and are also required for beige fat recruitment under thermal challenge, demonstrating both cell autonomous and non-cell autonomous roles in adaptive thermogenesis. Furthermore, mice bearing targeted ablation of these adipocytes exhibited glucose intolerance, while mice receiving exogenously supplied such cells manifested enhanced glucose utilization. Our studies uncover a unique adipocyte population in regulating beiging in adipose tissues and systemic glucose homeostasis.


Assuntos
Adipócitos , beta Catenina , Adipócitos/metabolismo , Adipogenia/fisiologia , Animais , Glucose/metabolismo , Mamíferos/metabolismo , Camundongos , Via de Sinalização Wnt/fisiologia , beta Catenina/genética , beta Catenina/metabolismo
5.
PLoS One ; 17(5): e0267931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35507629

RESUMO

BACKGROUND: Predicting reduced health-related quality of life (HRQoL) after resection of a benign or low-grade brain tumour provides the opportunity for early intervention, and targeted expenditure of scarce supportive care resources. We aimed to develop, and evaluate the performance of, machine learning (ML) algorithms to predict HRQoL outcomes in this patient group. METHODS: Using a large prospective dataset of HRQoL outcomes in patients surgically treated for low grade glioma, acoustic neuroma and meningioma, we investigated the capability of ML to predict a) HRQoL-impacting symptoms persisting between 12 and 60 months from tumour resection and b) a decline in global HRQoL by more than the minimum clinically important difference below a normative population mean within 12 and 60 months after resection. Ten-fold cross-validation was used to measure the area under the receiver operating characteristic curve (AUC), area under the precision-recall curve (PR-AUC), sensitivity, and specificity of models. Six ML algorithms were explored per outcome: Random Forest Classifier, Decision Tree Classifier, Logistic Regression, K Neighbours Classifier, Support Vector Machine, and Gradient Boosting Machine. RESULTS: The final cohort included 262 patients. Outcome measures for which AUC>0.9 were Appetite loss, Constipation, Nausea and vomiting, Diarrhoea, Dyspnoea and Fatigue. AUC was between 0.8 and 0.9 for global HRQoL and Financial difficulty. Pain and Insomnia achieved AUCs below 0.8. PR-AUCs were similar overall to the AUC of each respective classifier. CONCLUSIONS: ML algorithms based on routine demographic and perioperative data show promise in their ability to predict HRQoL outcomes in patients with low grade and benign brain tumours between 12 and 60 months after surgery.


Assuntos
Glioma , Neoplasias Meníngeas , Meningioma , Neuroma Acústico , Glioma/patologia , Glioma/cirurgia , Humanos , Aprendizado de Máquina , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Neuroma Acústico/cirurgia , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos
6.
BMC Med ; 20(1): 134, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35513801

RESUMO

BACKGROUND: Previous studies of primarily Western populations have reported contrasting associations of dairy consumption with certain cancers, including a positive association with prostate cancer and inverse associations with colorectal and premenopausal breast cancers. However, there are limited data from China where cancer rates and levels of dairy consumption differ importantly from those in Western populations. METHODS: The prospective China Kadoorie Biobank study recruited ~0.5 million adults from ten diverse (five urban, five rural) areas across China during 2004-2008. Consumption frequency of major food groups, including dairy products, was collected at baseline and subsequent resurveys, using a validated interviewer-administered laptop-based food frequency questionnaire. To quantify the linear association of dairy intake and cancer risk and to account for regression dilution bias, the mean usual consumption amount for each baseline group was estimated via combining the consumption level at both baseline and the second resurvey. During a mean follow-up of 10.8 (SD 2.0) years, 29,277 incident cancer cases were recorded among the 510,146 participants who were free of cancer at baseline. Cox regression analyses for incident cancers associated with usual dairy intake were stratified by age-at-risk, sex and region and adjusted for cancer family history, education, income, alcohol intake, smoking, physical activity, soy and fresh fruit intake, and body mass index. RESULTS: Overall, 20.4% of participants reported consuming dairy products (mainly milk) regularly (i.e. ≥1 day/week), with the estimated mean consumption of 80.8 g/day among regular consumers and of 37.9 g/day among all participants. There were significant positive associations of dairy consumption with risks of total and certain site-specific cancers, with adjusted HRs per 50 g/day usual consumption being 1.07 (95% CI 1.04-1.10), 1.12 (1.02-1.22), 1.19 (1.01-1.41) and 1.17 (1.07-1.29) for total cancer, liver cancer (n = 3191), female breast cancer (n = 2582) and lymphoma (n=915), respectively. However, the association with lymphoma was not statistically significant after correcting for multiple testing. No significant associations were observed for colorectal cancer (n = 3350, 1.08 [1.00-1.17]) or other site-specific cancers. CONCLUSION: Among Chinese adults who had relatively lower dairy consumption than Western populations, higher dairy intake was associated with higher risks of liver cancer, female breast cancer and, possibly, lymphoma.

7.
J Clin Lab Anal ; : e24476, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522153

RESUMO

BACKGROUND: The purpose of our study is to analyze the microbiological and clinical characteristics of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) that causes nosocomial infection. METHODS: We collected the carbapenem-resistant K. pneumoniae (CRKP) strains that caused nosocomial infection in a hospital in China and collected the relevant clinical data. We characterized these strains for their antimicrobial and virulence-associated phenotype and genotype and analyzed the clonal relatedness. We screened hypervirulent strains and compared them with non-hypervirulent strains. RESULTS: We retrospectively analyzed 62 CRKP strains that caused nosocomial infection in a tertiary hospital within 1 year, of which 41 (41/62, 66.1%) CRKP were considered as CR-hvKP. All CR-hvKP strains were multi-drug resistance (MDR) and the vast majority of isolates (39/41, 95.1%) were ST11 KPC-2-producing strains. Two hypermucoviscous isolates and 4 capsular types were found in 41 CR-hvKP. Twenty-nine isolates (29/41, 70.7%) showed hypervirulence in Galleria mellonella infection model. PFGE showed that ST11-KL47 CR-hvKP and ST11-KL64 CR-hvKP exhibited a high degree of clonality, while non-hypervirulent strains were not significant. CR-hvKP had higher positive rates of blaKPC-2 and blaCTX-M-65 and higher levofloxacin resistance (p < 0.001, p = 0.005 and p = 0.046, respectively) when compared to the non-hypervirulent strains. There was no significant difference between the two groups in terms of in-hospital mortality (7/41, 17.1% vs 5/21, 23.8%, p = 0.743). CONCLUSION: Our research finds that ST11 KPC-2-producing CR-hvKP is the main type of CRKP that caused nosocomial infection, and clonal spread has occurred. We provide more information about CR-hvKP in health care.

8.
Front Nutr ; 9: 833271, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35495958

RESUMO

Objective: The metabolic mechanism of harmful effects of red meat on the cardiovascular system is still unclear. The objective of the present study is to investigate the associations of self-reported red meat consumption with plasma metabolic markers, and of these markers with the risk of cardiovascular diseases (CVD). Methods: Plasma samples of 4,778 participants (3,401 CVD cases and 1,377 controls) aged 30-79 selected from a nested case-control study based on the China Kadoorie Biobank were analyzed by using targeted nuclear magnetic resonance to quantify 225 metabolites or derived traits. Linear regression was conducted to evaluate the effects of self-reported red meat consumption on metabolic markers, which were further compared with the effects of these markers on CVD risk assessed by logistic regression. Results: Out of 225 metabolites, 46 were associated with red meat consumption. Positive associations were observed for intermediate-density lipoprotein (IDL), small high-density lipoprotein (HDL), and all sizes of low-density lipoprotein (LDL). Cholesterols, phospholipids, and apolipoproteins within various lipoproteins, as well as fatty acids, total choline, and total phosphoglycerides, were also positively associated with red meat consumption. Meanwhile, 29 out of 46 markers were associated with CVD risk. In general, the associations of metabolic markers with red meat consumption and of metabolic markers with CVD risk showed consistent direction. Conclusions: In the Chinese population, red meat consumption is associated with several metabolic markers, which may partially explain the harmful effect of red meat consumption on CVD.

9.
Hepatol Res ; 2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35366388

RESUMO

AIM: Hepatocellular carcinoma (HCC) is common and causes many deaths worldwide. The aim of this study is to explore the mechanism by which long non-coding RNA FGD5-AS1 regulates HCC cell proliferation and stemness. METHODS: Tumor and normal adjacent tissues were harvested from HCC patients. Real-time quantitative reverse transcription-PCR was applied to examine the expression of FGD5-AS1, miR-223, Epithelial cell transforming sequence 2 (ECT2) and FAT1. The protein levels of ECT2, FAT1, proliferating cell nuclear antigen (PCNA), OCT4, CD133 and CD90 were analyzed by western blot. The localization of FGD5-AS1 was examined by Fluorescence in situ hybridization. Cell proliferation was analyzed with CCK-8 and colony formation assays. Spheroid formation was used for analyzing cell stemness. Gene interaction was examined by RNA immunoprecipitation and luciferase activity assays. A subcutaneous xenograft mouse model was established to analyze HCC growth and stemness in vivo. Immunohistochemistry staining was used to analyze the expression PCNA and OCT4 in subcutaneous tumors. RESULTS: FGD5-AS1 was upregulated in HCC and its high expression indicated poor prognosis of patients. High expression of FGD5-AS1 enhanced HCC cell proliferation and stemness. Knockdown of FGD5-AS1 restrained tumor growth and stemness in mice. FGD5-AS1 directly sponged miR-223 and promoted the expression of ECT2 and FAT1 in HCC. Both knockdown of miR-223 and overexpression of ECT2 and FAT1 reversed FGD5-AS1 silencing-mediated suppression of HCC cell proliferation and stemness. CONCLUSION: FGD5-AS1 directly sponged miR-223 and promoted the expression of ECT2 and FAT1 in HCC, thus enhancing HCC cell proliferation and stemness. Our study identifies potential prognostic biomarkers and therapeutic targets for HCC.

10.
PLoS Med ; 19(4): e1003967, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35452448

RESUMO

BACKGROUND: Taller adult height is associated with lower risks of ischemic heart disease in mendelian randomization (MR) studies, but little is known about the causal relevance of height for different subtypes of ischemic stroke. The present study examined the causal relevance of height for different subtypes of ischemic stroke. METHODS AND FINDINGS: Height-associated genetic variants (up to 2,337) from previous genome-wide association studies (GWASs) were used to construct genetic instruments in different ancestral populations. Two-sample MR approaches were used to examine the associations of genetically determined height with ischemic stroke and its subtypes (cardioembolic stroke, large-artery stroke, and small-vessel stroke) in multiple ancestries (the MEGASTROKE consortium, which included genome-wide studies of stroke and stroke subtypes: 60,341 ischemic stroke cases) supported by additional cases in individuals of white British ancestry (UK Biobank [UKB]: 4,055 cases) and Chinese ancestry (China Kadoorie Biobank [CKB]: 10,297 cases). The associations of genetically determined height with established cardiovascular and other risk factors were examined in 336,750 participants from UKB and 58,277 participants from CKB. In MEGASTROKE, genetically determined height was associated with a 4% lower risk (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.94, 0.99; p = 0.007) of ischemic stroke per 1 standard deviation (SD) taller height, but this masked a much stronger positive association of height with cardioembolic stroke (13% higher risk, OR 1.13 [95% CI 1.07, 1.19], p < 0.001) and stronger inverse associations with large-artery stroke (11% lower risk, OR 0.89 [0.84, 0.95], p < 0.001) and small-vessel stroke (13% lower risk, OR 0.87 [0.83, 0.92], p < 0.001). The findings in both UKB and CKB were directionally concordant with those observed in MEGASTROKE, but did not reach statistical significance: For presumed cardioembolic stroke, the ORs were 1.08 (95% CI 0.86, 1.35; p = 0.53) in UKB and 1.20 (0.77, 1.85; p = 0.43) in CKB; for other subtypes of ischemic stroke in UKB, the OR was 0.97 (95% CI 0.90, 1.05; p = 0.49); and for other nonlacunar stroke and lacunar stroke in CKB, the ORs were 0.89 (0.80, 1.00; p = 0.06) and 0.99 (0.88, 1.12; p = 0.85), respectively. In addition, genetically determined height was also positively associated with atrial fibrillation (available only in UKB), and with lean body mass and lung function, and inversely associated with low-density lipoprotein (LDL) cholesterol in both British and Chinese ancestries. Limitations of this study include potential bias from assortative mating or pleiotropic effects of genetic variants and incomplete generalizability of genetic instruments to different populations. CONCLUSIONS: The findings provide support for a causal association of taller adult height with higher risk of cardioembolic stroke and lower risk of other ischemic stroke subtypes in diverse ancestries. Further research is needed to understand the shared biological and physical pathways underlying the associations between height and stroke risks, which could identify potential targets for treatments to prevent stroke.


Assuntos
AVC Embólico , AVC Isquêmico , Acidente Vascular Cerebral , Adulto , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética
11.
Neurology ; 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35410902

RESUMO

BACKGROUND AND OBJECTIVES: Contemporary cardiovascular disease (CVD) risk prediction models are rarely applied in routine clinical practice in China due to substantial regional differences in absolute risks of major CVD types within China. Moreover, the inclusion of blood lipids in most risk prediction models also limits their use in the Chinese population. We developed 10-year CVD risk prediction models excluding blood lipids that may be applicable to diverse regions of China. METHODS: We derived sex-specific models separately for ischemic heart disease (IHD), ischemic stroke (IS), and hemorrhagic stroke (HS) in addition to total CVD in the China Kadoorie Biobank. Participants were aged 30-79 years without CVD at baseline. Predictors included age, systolic and diastolic blood pressure, use of blood pressure-lowering treatment, current daily smoker, diabetes, and waist circumference. Total CVD risks were combined in terms of conditional probability using the predicted risks of three submodels. Risk models were recalibrated in each region by two methods ("practical" and "ideal") and risk prediction was estimated before and after recalibration. RESULTS: Model derivation involved 489,596 individuals, including 45,947 IHD, 43,647 IS, and 11,168 HS cases during 11 years of follow-up. In women, the Harrell's C was 0.732 (95% CI 0.706-0.758), 0.759 (0.738-0.779), and 0.803 (0.778-0.827) for IHD, IS, and HS, respectively. The Harrell's C for total CVD was 0.734 (0.732-0.736), 0.754 (0.752-0.756), and 0.774 (0.772-0.776) for models before recalibration, after practical recalibration, and after ideal recalibration. The calibration performances improved after recalibration, with models after ideal recalibration showing the best model performances. The results for men were comparable to those for women. DISCUSSION: Our CVD risk prediction models yielded good discrimination of IHD and stroke subtypes in addition to total CVD without including blood lipids. Flexible recalibration of our models for different regions could enable more widespread use using resident health records covering the overall Chinese population. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that a prediction model incorporating accessible clinical variables predicts 10-year risk of ischemic heart disease, ischemic stroke, and hemorrhagic stroke in the Chinese population, age 30-79 years.

12.
Artigo em Inglês | MEDLINE | ID: mdl-35460564

RESUMO

BACKGROUND: There is an evidence gap about whether a low-risk lifestyle is as important as achieving blood pressure (BP) and random blood glucose (RBG) control. OBJECTIVES: To explore the long-term impacts and relative importance of low-risk lifestyle and health factors on the risk of all-cause and cancer mortality and macrovascular and microvascular complications among diabetic patients. METHODS: This study included 26,004 diabetes patients in the China Kadoorie Biobank. We defined five lifestyle factors (smoking, alcohol drinking, physical activity, fruits and vegetables intake, and waist-to-hip ratio) and two health factors (BP and RBG). Cox regression was used to yield adjusted hazard ratios (HRs) and confidence intervals (CIs) for individual and combined lifestyle and health factors with the risks of diabetes-related outcomes. RESULTS: There were 5,063 deaths, 6,848 macrovascular complications, and 2,055 microvascular complications that occurred during a median follow-up of 10.2 years. Combined low-risk lifestyle factors were associated with lower risk of all main outcomes, with HRs (95%CIs) for participants having 4-5 low-risk factors versus 0-1 of 0.50 (0.44 to 0.57) for all-cause mortality, 0.55 (0.43 to 0.71) for cancer mortality, 0.60 (0.54 to 0.67) for macrovascular complications, and 0.75 (0.62 to 0.91) for microvascular complications. The combined 4-5 low-risk lifestyle factors showed relative importance in predicting all-cause and cancer mortality and macrovascular complications. CONCLUSIONS: Assuming causality exists, our findings suggest that adopting a low-risk lifestyle should be regarded as important as achieving ideal BP and glycemic goals in the prevention and management of diabetes-related adverse outcomes.

13.
Eur J Nutr ; 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35445833

RESUMO

PURPOSE: There is limited and inconsistent evidence about the relationships of erythrocyte polyunsaturated fatty acids (PUFAs) with stroke and stroke types, particularly in China where the stroke rates are high. We aimed to investigate the associations of different erythrocyte PUFAs with incidence of total stroke, ischemic stroke (IS), and intracerebral hemorrhage (ICH) in Chinese adults. METHODS: In the prospective China Kadoorie Biobank, erythrocyte PUFAs were measured using gas chromatography in 10,563 participants who attended 2013-14 resurvey. After a mean follow-up of 3.8 years, 412 incident stroke cases (342 IS, 53 ICH) were recorded among 8,159 participants without prior vascular diseases or diabetes. Cox regression yielded adjusted hazard ratios (HRs) for stroke associated with 13 PUFAs. RESULTS: Overall, the mean body mass index was 24.0 (3.4) kg/m2 and the mean age was 58.1 (9.9) years. In multivariable analyses, 18:2n-6 was positively associated with ICH (HR = 2.33 [95% CIs 1.41, 3.82] for top versus bottom quintile, Ptrend = 0.007), but inversely associated with IS (0.69 [0.53,0.90], Ptrend = 0.027), while 20:3n-6 was positively associated with risk of IS (1.64 [1.32,2.04], Ptrend < 0.001), but not with ICH. Inverted-U shape curve associations were observed of 20:5n-3 with IS (Pnonlinear = 0.002) and total stroke (Pnonlinear = 0.008), with a threshold at 0.70%. After further adjustment for conventional CVD risk factors and dietary factors, these associations remained similar. CONCLUSION: Among relatively lean Chinese adults, erythrocyte PUFAs 18:2n-6, 20:3n-6 and 20:5n-3 showed different associations with risks of IS and ICH. These results would improve the understanding of stroke etiology.

14.
Lancet Reg Health West Pac ; 22: 100443, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35400017

RESUMO

Background: Pneumonia represents a public health problem of substantial health and economic burden. However, the evidence on the burden of adult pneumonia is limited in China. Methods: The China Kadoorie Biobank recruited 512,725 participants aged 30-79 years from five urban and five rural areas during 2004-2008. The current analyses included 506,086 participants who were alive in 2009. Pneumonia hospitalizations were ascertained through the health insurance system until December 31, 2017. Generalized linear models were used to examine the secular trends and regional and population variations in pneumonia hospitalization rate, mean length of hospital stay (LOS), and 30-day case fatality rate (CFR). Findings: A total of 27,879 participants with 36,567 pneumonia hospitalizations were identified with a mean follow-up time of 8·9 years. The unadjusted hospitalization rate was 8·4 (95% confidence interval [CI]: 8·3, 8·6) per 1000 person-years, with an increase of 15·5% annually from 4·2 (3·9, 4·4) in 2009 to 10·9 (10·6, 11·3) in 2017, after adjusting for age, sex, study area. The mean LOS was 8·8 (95% CI: 8·7, 8·9) days, with a slight decrease of 1·0% annually from 2009 to 2017. The average 30-day CFR remained practically unchanged at 2·4 (95% CI: 2·2, 2·5) deaths per 100 admissions. A clear seasonal pattern of pneumonia hospitalization rate was observed, and the hospitalization rate and CFR differed across regions and subpopulations of different ages and underlying conditions. Interpretation: There was an increasing hospitalization burden of pneumonia in Chinese adults, especially for adults aged ≥60 years or those with underlying conditions. Funding: The National Natural Science Foundation of China, the Kadoorie Charitable Foundation, the National Key R&D Program of China, the Chinese Ministry of Science and Technology. Translated abstract in Chinese: This translation in Chinese was submitted by the authors and we reproduce it as supplied. It has not been peer reviewed. Our editorial processes have only been applied to the original abstract in English, which should serve as reference for this manuscript. :, ., .:(China Kadoorie Biobank)2004-2008555030-79.506,086200911.20091120171231.,30,.:8.9, 27,879, 36,567.8.4 (95% CI:8.3, 8.6)/1000, ,, 20094.2 (3.9, 4.4)201710.9 (10.6, 11.3), 15.5%.8.8(95% CI:8.7, 8.9), 1.0%.30, 2.4(95% CI:2.2, 2.5)/100.;,, 30.:, ≥60.

15.
Anal Chem ; 94(13): 5293-5300, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35319873

RESUMO

An electrical resistance-based particle counter (ERPC) with simple operation and high resolution has proved to be a promising biosensing toolkit, whereas amplification-free ERPC biosensors are incapable of analyzing trace small molecules due to their relatively low sensitivity. In this work, click chemistry-mediated particle counting sensing of small-molecule hazards in food samples with high sensitivity was developed. In this strategy, unbound alkyne-functionalized polystyrene microspheres were collected by magnetic separation from the copper-ion-mediated click reaction between alkyne-functionalized polystyrene microspheres and azido-functionalized magnetic beads, which could be used as signal probes for the readout. This click chemistry-mediated ERPC biosensor converts the detection of targets to the quantification of copper ions or ascorbic acid by performing competitive immunoassay-based coordination chemistry and enzymatic reaction, respectively. The sensitivity of the ERPC biosensor has been improved by an order of magnitude due to the signal amplification effects of click chemistry, coordination adsorption, and enzyme catalysis. Furthermore, because of the efficient separation and enrichment of immunomagnetic beads and the robustness of click chemistry, the interference from food matrixes and immunoassay is effectively reduced, and thus, our strategy is exceedingly suitable for detecting trace targets in complex samples.


Assuntos
Técnicas Biossensoriais , Química Click , Alcinos/química , Cobre/química , Ácido Poliglutâmico
16.
Biosens Bioelectron ; 207: 114127, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35278785

RESUMO

Traditional magnetic relaxation switching (MRS) biosensors suffer from poor sensitivity and unsatisfactory stability. In this study, a polydopamine (PDA) nanoparticles (NPs)-Cu2+ chelate complex mediated signal conversion system and a Cu+-catalyzed click chemistry triggered magnetic signal amplification system were evaluated and dynamically integrated into an MRS biosensor. Owing to abundant functional groups and a large surface area, PDA NPs enabled the absorption of a large amount of Cu2+ ions by chelation. The residual Cu2+ ions can be reduced with sodium ascorbate to Cu+, which could initiate the click reaction between azide-functionalized magnetic NPs (MNPs) and alkyne-functionalized MNPs that resulted in the production of aggregated nanoclusters. The transverse relaxation time (T2) depends on the degree of aggregation of MNPs; T2 is expressed as the magnetic signal readout. In addition, PDA NPs can be easily conjugated with antibodies by mixing, thus providing a straightforward bridge that integrates the immunoassay and magnetic signal readout. Combined with the high capacity of PDA NPs for chelating Cu2+ and high efficiency of click reaction for changing the T2 signals, the PDA-MRS biosensor enables the detection of chlorpyrifos with a limit of detection of 0.084 ng/mL, providing 22-fold enhancement than traditional enzyme-linked immunosorbent assay (1.86 ng/mL). This demonstrates its great potential for the detection of hazardous chemical molecules in a complex sample matrix.


Assuntos
Técnicas Biossensoriais , Clorpirifos , Nanopartículas , Técnicas Biossensoriais/métodos , Quelantes , Química Click , Cobre/química , Indóis , Íons , Fenômenos Magnéticos , Polímeros
17.
J Med Chem ; 65(7): 5675-5689, 2022 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-35332774

RESUMO

Stereochemically and structurally complex cyclic dinucleotide-based stimulator of interferon genes (STING) agonists were designed and synthesized to access a previously unexplored chemical space. The assessment of biochemical affinity and cellular potency, along with computational, structural, and biophysical characterization, was applied to influence the design and optimization of novel STING agonists, resulting in the discovery of MK-1454 as a molecule with appropriate properties for clinical development. When administered intratumorally to immune-competent mice-bearing syngeneic tumors, MK-1454 exhibited robust tumor cytokine upregulation and effective antitumor activity. Tumor shrinkage in mouse models that are intrinsically resistant to single-agent therapy was further enhanced when treating the animals with MK-1454 in combination with a fully murinized antimouse PD-1 antibody, mDX400. These data support the development of STING agonists in combination with pembrolizumab (humanized anti-PD-1 antibody) for patients with tumors that are partially responsive or nonresponsive to single-agent anti-PD-1 therapy.


Assuntos
Proteínas de Membrana , Neoplasias , Animais , Citocinas , Humanos , Imunoterapia/métodos , Interferons , Camundongos , Neoplasias/tratamento farmacológico
18.
Food Chem ; 386: 132712, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35339078

RESUMO

In this work, a one-step homogeneous micro-orifice resistance immunoassay has been proposed for chlorpyrifos detection by integrating functionalized polystyrene (PS) microsphere probes with particle counting technology. The particle counter is highly sensitive and accurate for detecting the state of PS microspheres, where the particles of different states exhibit significant differences in resistance. The state of the functionalized PS microspheres is altered from dispersed to aggregated during the antigen-antibody recognition. Based on the degree of aggregation of the functionalized PS microsphere probes, chlorpyrifos can be quantitatively detected through the competitive immune response between PS antibodies and PS complete antigens. This one-step homogeneous micro-orifice resistance immunoassay simplified the procedures and greatly increased the sensitivity of detection, which has been successfully applied to detect chlorpyrifos in orange samples within 0.5 h, with the detection limit of 0.058 ng/mL.


Assuntos
Clorpirifos , Citrus sinensis , Anticorpos , Imunoensaio/métodos , Limite de Detecção , Microesferas , Poliestirenos
19.
Artigo em Inglês | MEDLINE | ID: mdl-35244853

RESUMO

China is facing increasing pressure to reduce CO2 emissions from energy consumption. Given this issue, understanding the characteristics, influencing factors, and trends can provide adequate information for decision-makers to solve the CO2 emission problem. This study analyzes the characteristics of CO2 emissions from energy consumption in 30 regions of China from 2005 to 2018 and applies the STIRPAT model to identify the impact of the influencing factors. Combined with the CO2 emission trend in 2030 as predicted by the ARIMA model, the key mitigation regions and strategies reduction have been determined. Results indicate that CO2 emissions have been increasing from 2005 to 2018 in China, thus showing the characteristic of the east being larger than the west spatially. Under the baseline scenario, these emissions will continue to rise in 2030. Carbon emissions intensity is declining, and the gap between provinces with the highest and lowest per capita CO2 emissions is widening. Although per capita GDP is significantly positively correlated with provinces, population is the key factor influencing more provinces, followed by the proportion of the secondary industry and urbanization rate. To achieve low-carbon sustainable development, Shandong, Shanxi, Inner Mongolia, Guangdong, Shaanxi, Xinjiang, and Ningxia are considered the key regions of concern for emission reduction. The heterogeneity of CO2 emission characteristics and influencing factors among regions provides a direction for the development of targeted and differentiated regional emission reduction strategies.

20.
J Nutr ; 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35234872

RESUMO

BACKGROUND: Lower consumption of whole grains is associated with higher risks of diabetes and coronary heart disease in Western populations, but evidence is still limited for stroke. Moreover, little is known in China, where the rates of cardiometabolic diseases are high and grain types consumed are different from Western countries. OBJECTIVES: To examine the associations between coarse grain (e.g., millet, corn and sorghum) consumption and incident cardiometabolic diseases among Chinese adults. METHODS: The prospective China Kadoorie Biobank enrolled > 0.5 million adults aged 30-79 years from ten urban and rural areas during 2004-2008. At baseline, consumption frequencies (in 5 categories from never to daily) of 12 major food groups, including coarse grains, were collected using a validated food frequency questionnaire. After a median of 11 years of follow-up, 17,149 cases of diabetes, 29,876 ischemic strokes, 6097 hemorrhagic strokes, and 6704 major coronary events were recorded among 461,047 participants without prevalence of major chronic diseases at baseline. Cox regression analyses were used to yield adjusted hazard ratios (HRs) for each disease associated with coarse grain consumption. RESULTS: Overall, 13.8% of participants reported regular consumption (i.e., ≥4 days/week, regular consumers) and 29.4% reported never or rarely consumption of coarse grains (i.e., non-consumers) at baseline. Compared with non-consumers, regular consumers had lower risks of diabetes (adjusted HR: 0.88; 95% CI: 0.78, 0.98) and ischemic stroke (0.86; 0.81, 0.93), but not hemorrhagic stroke (0.96; 0.76, 1.20) and major coronary events (0.95; 0.81, 1.12). For diabetes and ischemic stroke, each 100 g/day higher usual intake of coarse grains was associated with 14% (0.86; 0.76, 0.97) and 13% (0.87; 0.81, 0.94) lower risks, respectively, which were similar in various subgroups. CONCLUSIONS: In Chinese adults, higher coarse grain consumption is associated with lower risks of diabetes and ischemic stroke, supporting the promotion of coarse grain consumption in China.

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