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2.
Anal Bioanal Chem ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31761955

RESUMO

Vitamin A deficiency (VAD) is a major micronutrient deficiency in children. Although plasma and serum retinol levels are proposed as the key indicators of VAD, collecting and transporting plasma and serum are difficult and inconvenient in field studies. Dried blood spot (DBS) retinol has been used as an alternative to plasma retinol in several epidemiological and clinical studies. A limitation of methods that use DBS retinol is the instability and apparent loss of retinol in DBSs. Therefore, an accurate, reliable method for stabilizing retinol in DBSs and quantifying and comparing DBS retinol concentrations with equivalent plasma retinol levels is required. In this study, antioxidants on paper combined with vacuum treatment were found to greatly increase the stability of DBS retinol during 120 min of air drying and 30 days of room-temperature storage. A surrogate matrix of whole blood prepared using a mixture of human erythrocytes and 2% BSA in PBS was firstly used in DBS retinol determination based on the fact that retinol is excluded from erythrocytes. The method was linear in the concentration range of 0.04-300 µg/mL. Both the between-run (n = 5) and within-run (n = 6) precision (relative standard deviations, RSD%) were below 8.42%. The spiked recoveries at 3 concentrations ranged from 86.48 to 98.13%. The internal standard (IS)-normalized matrix factor (MF) was 99.72% with a RSD% of 10.50% (n = 3). The accuracy was calibrated using two National Institute of Standards and Technology (NIST) serum-generated calibrants at concentrations of 0.1962 and 0.3948 g/mL, and relative errors (RE% values) of 0.07% and 4.95% were found, respectively. A simple calibration model was first developed to convert DBS retinol concentration to the equivalent plasma retinol concentration, thereby enabling comparisons with clinical reference ranges and with studies using serum or plasma samples. Graphical abstract.

3.
Nanoscale ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769772

RESUMO

As a coordination polymer built of [Mo3S13]2- clusters, amorphous nanoscale MoSx (a-MoSx) is an attractive electrocatalyst for the hydrogen evolution reaction (HER) due to its abundant active sites and scalable synthesis. However, clarifying the internal catalytic mechanism and achieving even higher HER performance with scalable size are still challenging. Herein, a new hybrid catalyst of a-MoSx flakes decorated with Ni3S2 nanocrystals (size < 10 nm) has been successfully synthesized on 10 × 20 cm2-sized Ni foam by a portable hydrothermal route. As the strong interaction of [Mo3S13]2- clusters with Ni3S2 is evidenced by comprehensive binding state and Raman characterization, the polymerization effect of [Mo3S13]2- itself and the perfect interfaces between [Mo3S13]2- clusters and Ni3S2 are also confirmed by density functional theory calculations. These two factors greatly lower the absorption energy of hydrogen nearly to zero, leading to much improved HER activity. Current densities of 100 and 600 mA cm-2 are achieved at overpotentials of 181 and 246 mV, respectively, which are so far the highest values approaching practical applications. The findings of this work provide a fundamental reference about the catalytic origin of a-MoSx based catalysts, and shed light on the practical applications of non-precious electrocatalysts for their compatibility with low cost batch production.

4.
J Exp Clin Cancer Res ; 38(1): 429, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660998

RESUMO

BACKGROUND: miR-133a-3p has been recently discovered to be down-regulated in various human malignancies, including breast cancer, and reduced miR-133a-3p levels have been significantly associated with breast cancer cell growth and invasion. However, the regulatory mechanisms leading to abnormal expression of miR-133a-3p in breast cancer remain obscure. METHODS: qRT-PCR was applied to detect the expression of miR-133a-3p in breast cancer tissues and cell lines. Bisulfite sequencing was used to detect the degree of methylation of the miR-133a-3p promoter. The effects of miR-133a-3p on breast cancer in vitro were examined by cell proliferation assay, transwell assay, flow cytometry, and western blotting. Bioinformatic analysis, dual-luciferase assay and RIP assay were employed to identify the interaction between miR-133a-3p and MAML1. A xenograft model was used to show the metastasis of breast cancer cells. RESULTS: We confirmed that miR-133a-3p was silenced by DNA hypermethylation in breast cancer cell lines and tissues, which predicted poor prognosis in breast cancer patients, and reducing miR-133a-3p expression led to a significant increase in the migration, invasion, proliferation, and stemness of breast cancer cells in vitro. Mastermind-like transcriptional coactivator 1 (MAML1) was confirmed to be a target of miR-133a-3p involved in regulating breast cancer metastasis both in vitro and in vivo. Moreover, a series of investigations indicated that MAML1 initiated a positive feedback loop, which could up-regulate DNA methyltransferase 3A (DNMT3A) to promote hypermethylation of the miR-133a-3p promoter. CONCLUSION: Taken together, our findings revealed a novel miR-133a-3p/MAML1/DNMT3A positive feedback loop in breast cancer cells, which may become a potential therapeutic target for breast cancer.

5.
Medicine (Baltimore) ; 98(41): e17493, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593114

RESUMO

The aim of this study was to assess the bedside brain function monitoring of color density spectral array (CDSA) for early prognostic evaluation of coma patients in pediatric intensive care unit (PICU).Forty-two consecutive pediatric coma patients were enrolled. The individual conscious state was evaluated according to the Glasgow coma scale (GCS). CDSA parameters including CDSA pattern (CDSAP), sleep-wake cycle (SWC), sleep stage (SS), and drug-induced fast wave activity (DIFWA) were recorded. Three months later, prognosis was evaluated according to pediatric cerebral performance category (PCPC) score, based on which the patients were divided into FP-group (favorable prognosis) and PP-group (poor prognosis).The changeable type of CDSAP, appearance of SWC, SS, and DIFWA were significantly correlated with favorable prognosis. Both GCS and SWC were significantly correlated with the prognosis. However, there was substantial overlap in GCS between FP-group and PP-group. Although the absence of SWC was statistically an independent risk factor for poor prognosis but with a high false positive rate (0.143), a linear logistic regression showed the odds ratio of GCS for predicting prognosis was 0.93 (95% confidence interval: 0.48-1.80; P = .83) and that of SWC was 0.12 (95% confidence interval: 0.03-0.47; P = .03). Furthermore, the absence of SWC was correlated with poor prognosis in nonintracranial infection patients.Our study found that several CDSA factors are associated with prognosis of coma patients in PICU. SWC may be a potential indicator for evaluating the prognosis of coma patients in PICU.


Assuntos
Coma/diagnóstico , Monitores de Consciência/estatística & dados numéricos , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Testes Imediatos , Adolescente , Criança , Pré-Escolar , Colorimetria/métodos , Colorimetria/estatística & dados numéricos , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Modelos Logísticos , Masculino , Valor Preditivo dos Testes , Prognóstico
6.
Org Lett ; 21(20): 8285-8289, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31553197

RESUMO

A series of chalcogen-containing carborane derivatives were synthesized through a one-pot reaction. The nonconjugated six-membered ring of carborane-fused disulfide (1) can be electrochemically reduced to a dithiolate derivative. The five-membered ring of carborane-fused chalcogenophenes (2-4) showed aromaticity and considerable σ-π conjugation. The dicarborane chalcogenides (5-7) showed intramolecular charge-transfer-induced emission. These chalcogen-containing carborane derivatives provided a useful platform to study the electron interaction systematically and shed some light on the design of carborane-based optoelectronic materials.

7.
Cell Death Dis ; 10(9): 649, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501409

RESUMO

Breast cancer is the most prevalent cancer in women worldwide, which remains incurable once metastatic. Breast cancer stem cells (BCSCs) are a small subset of breast cancer cells, which are the radical cause of drug resistance, tumor relapse, and metastasis in breast cancer. The extracellular serine protease inhibitor serpinE2, also named protease nexin-1 (PN-1), contributes to enhanced metastasis of cancer cells mainly by remodeling the tumor matrix. In this study, we found that PN-1 was up-regulated in breast cancer, which promoted cell invasion, migration and stemness. Furthermore, by using specific inhibitors, we discovered that epidermal growth factor (EGF) up-regulated PN-1 in breast cancer cells through cascade activation of epidermal growth factor receptor (EGFR) to the activation of protein kinase Cδ (PKCδ), mitogen-activated protein kinase (MEK) and extracellular signal-related kinase (ERK), which finally led to the up-regulation of early growth response protein 1 (EGR1). Moreover, EGF signaling was further activated as a feedback of PN-1 up-regulation through PN-1 blocking HtrA1. Taken together, our findings revealed a novel signaling axis that up-regulated PN-1 expression in breast cancer cells, and the new mechanism of PN-1-promoted breast cancer metastasis, which may provide new insights into identifying novel therapeutic targets for breast cancer.

8.
BMJ Open ; 9(9): e031021, 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31501129

RESUMO

OBJECTIVE: To investigate the current situation of anaemia among children aged 6-23 months in a rural county in China, and to explore the influencing factors and the main causes of anaemia. DESIGN: A cross-sectional study. SETTING: Huzhu County in Qinghai Province, China PARTICIPANTS: We selected 38 sampled villages using Proportional to Population Size sampling method. We obtained the name list of children aged 6-23 months in each sampled village and planned to survey all the eligible children aged 6-23 months and their caregivers. PRIMARY AND SECONDARY OUTCOMES MEASURES: The prevalence of anaemia, the influencing factors of anaemia, the laboratory tests for biological causes of anaemia, including serum ferritin, soluble transferrin receptor, folic acid, homocysteine and vitamin B12. RESULTS: A total of 754 children aged 6-23 months and their caregivers were surveyed, and 183 anaemic children aged 12-23 months were collected venous blood sample. The anaemia prevalence of children aged 6-23 months in Huzhu County was 59.1%. Children of younger age (OR=0.968, 95% CI 0.940 to 0.998), Tibetan nationality (OR=3.123, 95% CI 1.473 to 6.623) and not introducing meat (OR=0.698, 95% CI 0.499 to 0.976) were more likely to be anaemic. More than 80% of children with anaemia were due to iron deficiency (ID), and 20.2% of them had both iron and folic acid deficiencies. CONCLUSIONS: The anaemia prevalence of children aged 6-23 months in Huzhu County was high and children of younger age, Tibetan nationality and not introducing meat were more likely to be anaemic. The main cause of anaemia was nutritional anaemia, with the vast majority being ID. Interventions of feeding counselling and nutrients supplements are appropriate and should be further strengthened. TRIAL REGISTRATION NUMBER: ChiCTRPRC12002444.

9.
Ecotoxicol Environ Saf ; 184: 109627, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31509782

RESUMO

The toxicities of heavy metals in sediments are related to their bioavailability, which is critical for deriving reliable sediment quality guidelines. To evaluate the bioavailability of the metals (Cd, Cu, Ni, Pb and Zn), sediments were collected from Taihu Lake, one of the largest and most important freshwater lakes in China. Concentrations of simultaneously extracted metals (1-M HCl extraction, CSEM) in the sediments, metals released from sediment to pore waters and accumulated by diffusive gradients in thin films (DGT, CDGT), and dissolved metals in the overlying water (COLW) were measured separately. Sediment toxicity was assessed with tubificids (Monopylephorus limosus) and chironomids (Chironomus kiiensis and Chironomus tentans). Significant relationships existed between the total metal concentrations and CSEM, CDGT, and COLW measurements (r2 = 0.43-0.95, n = 27, p < 0.001), with stronger relationships with CSEM (r2 = 0.91-0.95) than CDGT (r2 = 0.56-0.85) and COLW (r2 = 0.43-0.71). Risk quotients were derived by dividing CSEM by sediment quality guideline values (SQGVs), and by dividing both CDGT and COLW by water quality criteria (WQC). Toxicity of the sediments to the three species was better explained by the CSEM-based risk quotient than those derived from CDGT and COLW. The study indicated that DGT piston probes deployed face down in sediments did not accumulate metals in proportion to the bioavailable metal fraction that caused toxicity to these freshwater benthic organisms, and that single measurements of metals in overlying waters are not adequate for predicting risks of toxicity from sediments. The measurement of CSEM was determined to be effective for assessing the risk posed by the metals in the Taihu Lake sediments, but offered limited improvement over measurement of total metal concentrations.

10.
Small ; 15(45): e1902789, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31544354

RESUMO

Palladium diselenide (PdSe2 ) is an emerging 2D layered material with anisotropic optical/electrical properties, extra-high carrier mobility, excellent air stability, etc. So far, ultrathin PdSe2 is mainly achieved via mechanical exfoliation from its bulk counterpart, and the direct synthesis is still challenging. Herein, the synthesis of ultrathin 2D PdSe2 on conductive Au foil substrates via a facile chemical vapor deposition route is reported. Intriguingly, an anisotropic growth behavior is detected from the evolution of ribboned flakes with large length/width ratios, which is well explained from the orthorhombic symmetry of PdSe2 . A unique even-layered growth mode from 2 to 20 layers is also confirmed by the perfect combination of onsite scanning tunneling microscopy characterizations, through deliberately scratching the flake edge to expose both even and odd layers. This even-layered, ribboned 2D material is expected to serve as a perfect platform for exploring unique physical properties, and for developing high-performance electronic and optoelectronic devices.

11.
J Am Chem Soc ; 141(47): 18694-18703, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31558019

RESUMO

Two-dimensional (2D) metallic transition metal dichalcogenides (MTMDCs) have attracted tremendous interest due to their intriguing physical properties and broad application potential. However, batch production of high-quality 2D MTMDCs based on existing synthesis on 2D surfaces remains a huge challenge. Herein, a universal synthetic route for the scalable synthesis of high-quality 2D MTMDC (e.g., TaS2, V5S8, and NbS2) nanosheets using microcrystalline NaCl crystals as templates via a facile chemical vapor deposition method is reported. Obviously, this synthetic route is perfectly compatible with a facile water dissolution-filtration process for obtaining high-purity MTMDC nanosheet powders. Representatively, a thickness-uniform 1T-TaS2 nanosheet product can be achieved that shows unexceptionable dispersibility in ethanol, which allows its assembly onto arbitrary substrates/electrodes for high-performance energy-related applications, herein serving as a high-performance electrocatalyst for the hydrogen evolution reaction. This work sheds light on the batch production, green transfer, and energy-related application of 2D MTMDC materials.

13.
Nat Commun ; 10(1): 4263, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537790

RESUMO

Mesostriatal dopaminergic neurons possess extensively branched axonal arbours. Whether action potentials are converted to dopamine output in the striatum will be influenced dynamically and critically by axonal properties and mechanisms that are poorly understood. Here, we address the roles for mechanisms governing release probability and axonal activity in determining short-term plasticity of dopamine release, using fast-scan cyclic voltammetry in the ex vivo mouse striatum. We show that brief short-term facilitation and longer short term depression are only weakly dependent on the level of initial release, i.e. are release insensitive. Rather, short-term plasticity is strongly determined by mechanisms which govern axonal activation, including K+-gated excitability and the dopamine transporter, particularly in the dorsal striatum. We identify the dopamine transporter as a master regulator of dopamine short-term plasticity, governing the balance between release-dependent and independent mechanisms that also show region-specific gating.

14.
Int J Syst Evol Microbiol ; 69(11): 3414-3419, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31380736

RESUMO

A Gram-negative bacterium, namely strain ANRC-JHZ47T, was isolated from a seawater sample collected at Biological Bay, Fildes Peninsula, Antarctica. Cells of strain ANRC-JHZ47T were rod-shaped and motile by a single polar flagellum. Strain ANRC-JHZ47T was aerobic, oxidase-negative, and catalase-positive. The strain grew at 4-37 °C (optimum, 25 °C), pH at 3.5-10.0 (optimum, pH 5.5) and in NaCl at 1-7.0 % (w/v; optimum, 2-3 %). Strain ANRC-JHZ47T used Q-8 as the predominant respiratory quinone. Its predominant fatty acids were C16 : 0 (21.9 %), C12 : 0 (12.6 %), C19 : 0cyclo ω8c (12.4 %), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c; 13.1 %), C10 : 0 3-OH (11.3 %) and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c; 6.0 %). Its major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, one unidentified aminolipid and five unknown polar lipids. The DNA G+C content was 42.6 mol%. Strain ANRC-JHZ47T showed the highest 16S rRNA gene sequence similarity to Marinomonas arenicola KMM 3893T (97.9 %), followed by Marinomonas primoryensis KMM 3633T (97.6 %), Marinomonas profundimaris D104T (97.2 %) and Marinomonas pollencensis IVIA-Po-185T (97.0 %). Furthermore, the average nucleotide identity values between strain ANRC-JHZ47T and M. arenicola KMM 3893T, M. primoryensis KMM 3633T and M. profundimaris D104T were 79.8, 74.0, and 74.1 %, respectively. The in silico DNA-DNA hybridization values between them were 22.5±2.5, 20.4±2.3 and 19.9±2.3 %, respectively. Based on the results of phenotypic and phylogenetic analyses, strain ANRC-JHZ47T is considered to represent a novel species of the genus Marinomonas, for which the name Marinomonas flavescens sp. nov. is proposed. The type strain is ANRC-JHZ47T (=MCCC 1K03604T=KCTC 72113T).


Assuntos
Marinomonas/classificação , Filogenia , Água do Mar/microbiologia , Regiões Antárticas , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Marinomonas/isolamento & purificação , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/química
15.
Sci Adv ; 5(8): eaaw8337, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31448331

RESUMO

Directly incorporating heteroatoms into the hexagonal lattice of graphene during growth has been widely used to tune its electrical properties with superior doping stability, uniformity, and scalability. However the introduction of scattering centers limits this technique because of reduced carrier mobilities and conductivities of the resulting material. Here, we demonstrate a rapid growth of graphitic nitrogen cluster-doped monolayer graphene single crystals on Cu foil with remarkable carrier mobility of 13,000 cm2 V-1 s-1 and a greatly reduced sheet resistance of only 130 ohms square-1. The exceedingly large carrier mobility with high n-doping level was realized by (i) incorporation of nitrogen-terminated carbon clusters to suppress the carrier scattering and (ii) elimination of all defective pyridinic nitrogen centers by oxygen etching. Our study opens up an avenue for the growth of high-mobility/conductivity doped graphene with tunable work functions for scalable graphene-based electronic and device applications.

17.
Adv Mater ; 31(37): e1903176, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31379103

RESUMO

Covalent organic frameworks (COF) or metal-organic frameworks have attracted significant attention for various applications due to their intriguing tunable micro/mesopores and composition/functionality control. Herein, a coordination-induced interlinked hybrid of imine-based covalent organic frameworks and Mn-based metal-organic frameworks (COF/Mn-MOF) based on the MnN bond is reported. The effective molecular-level coordination-induced compositing of COF and MOF endows the hybrid with unique flower-like microsphere morphology and superior lithium-storage performances that originate from activated Mn centers and the aromatic benzene ring. In addition, hollow or core-shell MnS trapped in N and S codoped carbon (MnS@NS-C-g and MnS@NS-C-l) are also derived from the COF/Mn-MOF hybrid and they exhibit good lithium-storage properties. The design strategy of COF-MOF hybrid can shed light on the promising hybridization on porous organic framework composites with molecular-level structural adjustment, nano/microsized morphology design, and property optimization.

18.
Chemistry ; 25(59): 13472-13478, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31393035

RESUMO

A series of water-soluble cationic chalcogenoviologen-based photosensitizers for photodynamic antimicrobial therapy (PDAT) is reported. The Se-containing derivatives (SeMV2+ ) 5 b and 6 b showed good antimicrobial activities due to the presence of chalcogen atoms and a cationic scaffold. The former efficiently enhanced the generation of reactive oxygen species (ROS), and the latter facilitated the ROS delivery to bacteria, resulting in their death. Interestingly, alkyl-modified photosensitizers showed higher antimicrobial activities than commonly reported photosensitizers with quaternary ammonium (QA) groups. In particular, the SeMV2+ (6 b) with excellent antibacterial activities efficiently promoted the healing of infected wounds in mice. Simple yet novel, nontoxic and biocompatible chalcogenoviologens provided a promising strategy to develop new efficient photosensitizers for photodynamic antimicrobial therapy and skin regeneration.


Assuntos
Anti-Infecciosos/química , Cátions/química , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/química , Pele/fisiopatologia , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Camundongos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Regeneração
19.
Plant Biotechnol J ; 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31350935

RESUMO

Sugar transporters are necessary to transfer hexose from cell wall spaces into parenchyma cells to boost hexose accumulation to high concentrations in fruit. Here, we have identified an apple hexose transporter (HTs), MdHT2.2, located in the plasma membrane, which is highly expressed in mature fruit. In a yeast system, the MdHT2.2 protein exhibited high 14 C-fructose and 14 C-glucose transport activity. In transgenic tomato heterologously expressing MdHT2.2, the levels of both fructose and glucose increased significantly in mature fruit, with sugar being unloaded via the apoplastic pathway, but the level of sucrose decreased significantly. Analysis of enzyme activity and the expression of genes related to sugar metabolism and transport revealed greatly up-regulated expression of SlLIN5, a key gene encoding cell wall invertase (CWINV), as well as increased CWINV activity in tomatoes transformed with MdHT2.2. Moreover, the levels of fructose, glucose and sucrose recovered nearly to those of the wild type in the sllin5-edited mutant of the MdHT2.2-expressing lines. However, the overexpression of MdHT2.2 decreased hexose levels and increased sucrose levels in mature leaves and young fruit, suggesting that the response pathway for the apoplastic hexose signal differs among tomato tissues. The present study identifies a new HTs in apple that is able to take up fructose and glucose into cells and confirms that the apoplastic hexose levels regulated by HT controls CWINV activity to alter carbohydrate partitioning and sugar content.

20.
Br J Sports Med ; 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296585

RESUMO

BACKGROUND: Few studies have examined the associations between physical activity (PA), sedentary behaviour (SB) and risk of colorectal neoplasia (CN). METHODS: We systematically searched Medline, Embase, PsyInfo, Cochrane and other sources from their inception to 30 September 2018 for cohort, case-control and cross-sectional studies that evaluated these associations in asymptomatic, average-risk subjects. Random-effect models were used to estimate relative risks (RRs) of any-type CN, advanced CN, and non-advanced CN, respectively, in individuals with the highest versus the lowest level of PA and SB. Dose-response analyses and subgroup analyses were conducted. The I2 statistic was used to examine heterogeneity among studies. RESULTS: We identified 32 observational studies, including 17 cross-sectional studies, 10 case-control studies and five longitudinal studies. PA (highest vs lowest) was inversely associated with risk for any-type CN (n=23 studies) and advanced CN (n=15 studies), with a RR of 0.77 (95% CI=0.71 to 0.83, I2=57.5%) and 0.73 (95% CI=0.63 to 0.82, I2=45.5%), respectively. There was no association between PA and non-advanced CN (n=5 studies). There was an as association between PA and any-type CN in both sexes, and also for the distal colon. We found no dose-response relationship between PA and any-type or advanced CN. Based on three studies identified, SB time (longest vs shortest) was associated with an increased risk of advanced CN (RR=1.24, 95% CI 1.04 to 1.49, I2=14.4%). No publication bias was detected by Begg's test. CONCLUSION: We report a 23% lower relative risk of any type of CN and a 27% lower risk of advanced CN in people with the highest level of PA compared with those in the lowest.

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