High Thermoelectric Performance of Non-Stoichiometric and Oriented GeTe Thin Films.

The increasing demand for micro-thermoelectric coolers and generators promotes the research on thermoelectric (TE) thin films. As a promising medium-temperature TE material, GeTe has attracted wide attention recently. However, the thermoelectric performance of thin-film GeTe remains inferior. Herein, oriented GeTe films with excessive Ge are obtained by magnetron co-sputtering technique, which can not only reduce the carrier concentration but also increase the carrier mobility, maintaining the high electrical conductivity of GeTe. Furthermore, higher structural symmetry and grain boundary scattering enhance the Seebeck coefficient of oriented GeTe films. As a result, the power factor (PF) value can reach as high as 2848 µW m-1 K-2 at room temperature and increase to 5263 µW m-1 K-2 at 600 K. Furthermore, a TE device with the Ge-rich GeTe thin film is fabricated and the maximum output power density (power per unit area) reaches 0.3 W cm-2 at ΔT = 250 K. This work demonstrates that the stoichiometry and orientation modulations are effective strategies to improve the thermoelectric performance of GeTe thin films.

A sensitive and rapid electrochemical biosensor for sEV-miRNA detection based on domino-type localized catalytic hairpin assembly.

Small extracellular-vesicule-associated microRNA (sEV-miRNA) is an important biomarker for cancer diagnosis. However, rapid and sensitive detection of low-abundance sEV-miRNA in clinical samples is challenging. Herein, a simple electrochemical biosensor that uses a DNA nanowire to localize catalytic hairpin assembly (CHA), also called domino-type localized catalytic hairpin assembly (DT-LCHA), has been proposed for sEV-miRNA1246 detection. The DT-LCHA offers triple amplification, (i). CHA system was localized in DNA nanowire, which shorten the distance between hairpin substrate, inducing the high collision efficiency of H1 and H2 and domino effect. Then, larger numbers of CHAs were triggered, capture probe bind DT-LCHA by exposed c sites. (ii) The DNA nanowire can load large number of electroactive substance RuHex as amplified electrochemical signal tags. (iii) multiple DT-LCHA was carried by the DNA nanowire, only one CHA was triggered, the DNA nanowire was trapped by the capture probe, which greatly improve the detection sensitivity, especially when the target concentration is extremely low. Owing to the triple signal amplification in this strategy, sEV-miRNA at a concentration of as low as 24.55 aM can be detected in 20 min with good specificity. The accuracy of the measurements was also confirmed using reverse transcription quantitative polymerase chain reaction. Furthermore, the platform showed good performance in discriminating healthy donors from patients with early gastric cancer (area under the curve [AUC]: 0.96) and was equally able to discriminate between benign gastric tumors and early cancers (AUC: 0.77). Thus, the platform has substantial potential in biosensing and clinical diagnosis.

A simple and sensitive electrochemical biosensor for circulating tumor cell determination based on dual-toehold accelerated catalytic hairpin assembly.

Tumor cells in blood circulation (CTCs) are vital biomarkers for noninvasive cancer diagnosis. We developed a simple and sensitive electrochemical biosensor based on dual-toehold accelerated catalytic hairpin assembly (DCHA) to distinguish CTCs from blood cells. In the presence of CTCs, the aptamer probe initiates the DCHA process, which produces amplified electrochemical signals. Compared with conventional catalytic hairpin assembly (CHA), the proposed DCHA showed high sensitivity, which led to a broader working range of 10-1000 cells mL-1 with a limit of detection of 4 cells mL-1. Furthermore, our method exhibited an excellent capability of distinguishing malignant breast cancers from healthy people, with a sensitivity of 97.4%. In summary, we have established an enzyme-free, easy-to-operate, and nondisruptive method for detecting circulating tumor cells in blood circulation based on the DCHA strategy. Its versatility and simplicity will make it more widely used in clinical diagnosis and biomedical research.

Understanding of transverse spin angular momentum in tightly focused linearly polarized vortex beams.

Spin angular momentum (SAM) is widely used in spin-dependent unidirectional optical interfaces, optical manipulation, integrated optical signal processing, laser structuring and other fields, but its physical mechanism has not been fully understood so far. In this work, we investigate the three-dimensional (3D) SAM in tightly focused x-polarized first-order vortex beams from the perspectives of light field itself, phase distribution, and focusing propagation. It is shown that the distribution of three orthogonal components of SAM at the focal plane has pseudo two-fold rotational symmetry, because the cycloidal rotation of the electric field of the tightly focused vortex beam is opposite. The 3D SAM distribution in the focal region is visualized by mapping the 3D distribution of state of polarization (SoP). In addition, a principle experimental method for identifying the transverse SAM by using the direction of particle's rotation axis in optical tweezers is proposed.

Localized DNA tetrahedrons assisted catalytic hairpin assembly for the rapid and sensitive profiling of small extracellular vesicle-associated microRNAs.

The profiling of small extracellular vesicle-associated microRNAs (sEV-miRNAs) plays a vital role in cancer diagnosis and monitoring. However, detecting sEV-miRNAs with low expression in clinical samples remains challenging. Herein, we propose a novel electrochemical biosensor using localized DNA tetrahedron-assisted catalytic hairpin assembly (LDT-CHA) for sEV-miRNA determination. The LDT-CHA contained localized DNA tetrahedrons with CHA substrates, leveraging an efficient localized reaction to enable sensitive and rapid sEV-miRNA measurement. Based on the LDT-CHA, the proposed platform can quantitatively detect sEV-miRNA down to 25 aM in 30 min with outstanding specificity. For accurate diagnosis of gastric cancer patients, a combination of LDT-CHA and a panel of four sEV-miRNAs (sEV-miR-1246, sEV-miR-21, sEV-miR-183-5P, and sEV-miR-142-5P) was employed in a gastric cancer cohort. Compared with diagnosis with single sEV-miRNA, the proposed platform demonstrated a higher accuracy of 88.3% for early gastric tumor diagnoses with higher efficiency (AUC: 0.883) and great potential for treatment monitoring. Thus, this study provides a promising method for the bioanalysis and determination of the clinical applications of LDT-CHA.

Metabolomic profiling reveals serum L-pyroglutamic acid as a potential diagnostic biomarker for systemic lupus erythematosus.

OBJECTIVE: The spectrum of clinical manifestations and serological phenomena of SLE is heterogeneous among patients and even changes over time unpredictably in individual patients. For this reason, clinical diagnosis especially in complicated or atypical cases is often difficult or delayed leading to poor prognosis. Despite the medical progress nowadays in the understanding of SLE pathogenesis, disease-specific biomarkers for SLE remain an outstanding challenge. Therefore, we undertook this study to investigate potential biomarkers for SLE diagnosis. METHODS: Serum samples from 32 patients with SLE and 25 gender-matched healthy controls (HCs) were analysed by metabolic profiling based on liquid chromatography-tandem mass spectrometry metabolomics platform. The further validation for the potential biomarker was performed in an independent set consisting of 36 SLE patients and 30 HCs. RESULTS: The metabolite profiles of serum samples allowed differentiation of SLE patients from HCs. The levels of arachidonic acid, sphingomyelin (SM) 24:1, monoacylglycerol (MG) 17:0, lysophosphatidyl ethanolamine (lysoPE) 18:0, lysoPE 16:0, lysophosphatidyl choline (lysoPC) 20:0, lysoPC 18:0 and adenosine were significantly decreased in SLE patients, and the MG 20:2 and L-pyroglutamic acid were significantly increased in SLE group. In addition, L-pyroglutamic acid achieved an area under the receiver-operating characteristic curve of 0.955 with high sensitivity (97.22%) and specificity (83.33%) at the cut-off of 61.54 µM in the further targeted metabolism, indicating diagnostic potential. CONCLUSION: Serum metabolic profiling is differential between SLE patients and HCs and depicts increased L-pyroglutamic acid as a promising bitformatomarker for SLE.

Angular momentum separation in focused fractional vector beams for optical manipulation.

The generation, propagation, and applications of different types of integer vector beams have been extensively investigated. However, little attention focuses on the photophysical and photomechanical properties of the fractional vector beam (FVB). Herein, we theoretically and experimentally investigate the spin angular momentum (SAM) separation and propagation characteristics of weakly focused FVBs. It is demonstrated that such a beam carrying no SAM leads to both the transverse separation of SAM and the special intensity patterns in the focal region. Furthermore, we study the intensity, SAM, and orbital angular momentum (OAM) distributions of the tightly focused FVBs. It is shown that both three-dimensional SAM and OAM are spatially separated in the focal region of tightly focused FVBs. We investigate the optical forces, spin torques, and orbital torques on a dielectric Rayleigh particle produced by the focused FVBs. The results reveal that asymmetrical spinning and orbiting motions of optically trapped particles can be realized by manipulating FVBs.

Nonlinear accelerated orbiting motions of optical trapped particles through two-photon absorption.

Vortex beams carrying optical angular momentum (AM) could drive the orbital motion of a small particle around the optical axis. In general, the orbital rotation speed of trapped particles increases linearly with the increasing laser power. Beyond the linear optics regime, in this work, we investigate both the optical force and torque on a two-photon absorbing Rayleigh particle produced by the tightly focused femtosecond-pulsed circularly polarized vortex beam. Different from the trapping dynamics of particles without two-photon absorption (TPA), it is shown that the orbital motion of trapped particles with TPA accelerates nonlinearly as the laser power increases. Moreover, the orbital motion acceleration of trapped particles is proportional to the TPA coefficient. The corresponding underlying mechanism is discussed in detail. Our results may find interesting applications in the characterization of the optical nonlinearity of a single nanoparticle, and AM manipulation and particle transportation in the nonlinear optics regime.

The effect of previous eradication failure on antibiotic resistance of Helicobacter pylori: A retrospective study over 8 years in Beijing.

BACKGROUND: Antibiotic resistance is the main cause of Helicobacter pylori (H. pylori) treatment failure. This study aimed to explore the characteristics of antibiotic resistance of H. pylori isolates in Beijing in the last 8 years and to estimate the impact of previous eradication failure on resistance patterns. MATERIALS AND METHODS: This retrospective study included data from a single center in Beijing from 2013 to 2020. Antibiotic susceptibility of 365 clinical H. pylori isolates was tested for amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline. The characteristics of the included patients and their previous eradication history were collected. Primary and secondary resistance rates of H. pylori to the six antibiotics and the impact of previous eradication failure on antibiotic resistance patterns were analyzed. RESULTS: The overall primary resistance rates of amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline were 0.7%, 55.2%, 68.0%, 49.7%, 64.5%, and 0%, with no significant increase during the observed period; while the secondary resistance rates were 3.2%, 96.7%, 90.7%, 93.1%, 80.0%, and 0%, respectively. The secondary resistance rate of clarithromycin (p < .001), metronidazole (p = .001), and levofloxacin (p < .001) significantly increased to 100% as the number of previous eradication therapies increased and exhibited a linear association. For strains naive to eradication, only 6.8% were susceptible to all the antibiotics, while 32.4% were single resistant, and 60.8% dual or multiple resistant. Clarithromycin+metronidazole+fluoroquinolone multiple resistance was the predominant pattern (0 course: 21.6%, 1 course: 37.5%, 2 courses: 56.1%, ≥3 courses: 71.1%; p < .001) for patients with treatment failure. The prevalence of dual or multiple-resistance patterns increased significantly as the number of previous therapies increased. CONCLUSIONS: The prevalence of primary and secondary resistance rates of clarithromycin, metronidazole, moxifloxacin, and levofloxacin were high in Beijing. Multiple-resistance patterns were common after treatment failure. Resistance rates of amoxicillin and tetracycline remained low and stable.

Inorganic Photonic Microspheres with Localized Concentric Ordering for Deep Pattern Encoding and Triple Sensory Microsensor.

Photonic microspheres offer building units with unique topological structures and specific optical functions for diverse applications. Here, a new class of inorganic photonic microspheres with superior robustness, optical and electrical properties is reported by introducing a unique localized concentric ordering architecture and chemical interaction, which further serve as building blocks for deep pattern encoding and multiple sensory optoelectronic devices. Benefiting from localized concentric ordering architecture, the resultant photonic microspheres demonstrate orientation- and angle-independent structural colors. Notably, the formation of well-combined lamellae inorganic layers by chemical interaction grants the microspheres superior mechanical robustness, excellent solvent resistance, thermal stability, and multiple optoelectronic properties simultaneously, rarely seen in previous reports. Owing to these merits, such microspheres are used to construct diverse encoded photonic patterns for anti-counterfeiting applications. Interestingly, cross-communication among neighboring microspheres creates complex photonic sub-patterns, which provide "fingerprint information" with deep encryption security. Moreover, a single photonic microsphere-based optoelectronic microsensor is demonstrated for the first time, which achieves appealing application for real-time health monitoring and safety warning toward triple environmental stimuli. This work not only provides a new kind of robust, multifunctional photonic material, but also opens a new avenue for their uses as complexed pattern encoding and multi-parametric sensing platforms.

Disordered intestinal microbes are associated with the activity of Systemic Lupus Erythematosus.

Intestinal dysbiosis is implicated in Systemic Lupus Erythematosus (SLE). However, the evidence of gut microbiome changes in SLE is limited, and the association of changed gut microbiome with the activity of SLE, as well as its functional relevance with SLE still remains unknown. Here, we sequenced 16S rRNA amplicon on fecal samples from 40 SLE patients (19 active patients, 21 remissive patients), 20 disease controls (Rheumatoid Arthritis (RA) patients), and 22 healthy controls (HCs), and investigated the association of functional categories with taxonomic composition by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). We demonstrated SLE patients, particularly the active patients, had significant dysbiosis in gut microbiota with reduced bacterial diversity and biased community constitutions. Amongst the disordered microbiota, the genera Streptococcus, Campylobacter, Veillonella, the species anginosus and dispar, were positively correlated with lupus activity, while the genus Bifidobacterium was negatively associated with the disease activity. PICRUSt analysis showed metabolic pathways were different between SLE and HCs, and also between active and remissive SLE patients. Moreover, we revealed that a random forest model could distinguish SLE from RA and HCs (area under the curve (AUC) = 0.792), and another random forest model could well predict the activity of SLE patients (AUC = 0.811). In summary, SLE patients, especially the active patients, show an apparent dysbiosis in gut microbiota and its related metabolic pathways. Amongst the disordered microflora, four genera and two species are associated with lupus activity. Furthermore, the random forest models are able to diagnose SLE and predict disease activity.

Hybrid molecules of scutellarein and tertramethylpyrazine's active metabolites for ischemic stroke.

A series of hybrid molecules of scutellarein and tertramethylpyrazine's active metabolites have been synthesized. Compared to the original compound, these prepared compounds exhibited higher water solubility, more appropriate logP and better stability. Importantly, compounds 11b, 11d and 11e showed improved neuroprotective activity against the H2O2-induced cell death in PC12 cells, and better antithrombosis activity. The optimized compound 11b was further evaluated by cerebral ischemia/ reperfusion in the middle cerebral artery occlusion (MCAO) model, the results showed that the compound could significantly reduce the infarct area and decrease the neuronal cell damage in CA1 pyramidal neurons. Overall, we demonstrated that the twin drug strategy could be applied in the development of agents for the treatment of ischemic stroke.

Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study.

BACKGROUND: The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear. METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a large, epidemiological cohort study of individuals aged 35-70 years (enrolled between Jan 1, 2003, and March 31, 2013) in 18 countries with a median follow-up of 7·4 years (IQR 5·3-9·3). Dietary intake of 135 335 individuals was recorded using validated food frequency questionnaires. The primary outcomes were total mortality and major cardiovascular events (fatal cardiovascular disease, non-fatal myocardial infarction, stroke, and heart failure). Secondary outcomes were all myocardial infarctions, stroke, cardiovascular disease mortality, and non-cardiovascular disease mortality. Participants were categorised into quintiles of nutrient intake (carbohydrate, fats, and protein) based on percentage of energy provided by nutrients. We assessed the associations between consumption of carbohydrate, total fat, and each type of fat with cardiovascular disease and total mortality. We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random intercepts to account for centre clustering. FINDINGS: During follow-up, we documented 5796 deaths and 4784 major cardiovascular disease events. Higher carbohydrate intake was associated with an increased risk of total mortality (highest [quintile 5] vs lowest quintile [quintile 1] category, HR 1·28 [95% CI 1·12-1·46], ptrend=0·0001) but not with the risk of cardiovascular disease or cardiovascular disease mortality. Intake of total fat and each type of fat was associated with lower risk of total mortality (quintile 5 vs quintile 1, total fat: HR 0·77 [95% CI 0·67-0·87], ptrend<0·0001; saturated fat, HR 0·86 [0·76-0·99], ptrend=0·0088; monounsaturated fat: HR 0·81 [0·71-0·92], ptrend<0·0001; and polyunsaturated fat: HR 0·80 [0·71-0·89], ptrend<0·0001). Higher saturated fat intake was associated with lower risk of stroke (quintile 5 vs quintile 1, HR 0·79 [95% CI 0·64-0·98], ptrend=0·0498). Total fat and saturated and unsaturated fats were not significantly associated with risk of myocardial infarction or cardiovascular disease mortality. INTERPRETATION: High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. Global dietary guidelines should be reconsidered in light of these findings. FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).

Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study.

BACKGROUND: The association between intake of fruits, vegetables, and legumes with cardiovascular disease and deaths has been investigated extensively in Europe, the USA, Japan, and China, but little or no data are available from the Middle East, South America, Africa, or south Asia. METHODS: We did a prospective cohort study (Prospective Urban Rural Epidemiology [PURE] in 135 335 individuals aged 35 to 70 years without cardiovascular disease from 613 communities in 18 low-income, middle-income, and high-income countries in seven geographical regions: North America and Europe, South America, the Middle East, south Asia, China, southeast Asia, and Africa. We documented their diet using country-specific food frequency questionnaires at baseline. Standardised questionnaires were used to collect information about demographic factors, socioeconomic status (education, income, and employment), lifestyle (smoking, physical activity, and alcohol intake), health history and medication use, and family history of cardiovascular disease. The follow-up period varied based on the date when recruitment began at each site or country. The main clinical outcomes were major cardiovascular disease (defined as death from cardiovascular causes and non-fatal myocardial infarction, stroke, and heart failure), fatal and non-fatal myocardial infarction, fatal and non-fatal strokes, cardiovascular mortality, non-cardiovascular mortality, and total mortality. Cox frailty models with random effects were used to assess associations between fruit, vegetable, and legume consumption with risk of cardiovascular disease events and mortality. FINDINGS: Participants were enrolled into the study between Jan 1, 2003, and March 31, 2013. For the current analysis, we included all unrefuted outcome events in the PURE study database through March 31, 2017. Overall, combined mean fruit, vegetable and legume intake was 3·91 (SD 2·77) servings per day. During a median 7·4 years (5·5-9·3) of follow-up, 4784 major cardiovascular disease events, 1649 cardiovascular deaths, and 5796 total deaths were documented. Higher total fruit, vegetable, and legume intake was inversely associated with major cardiovascular disease, myocardial infarction, cardiovascular mortality, non-cardiovascular mortality, and total mortality in the models adjusted for age, sex, and centre (random effect). The estimates were substantially attenuated in the multivariable adjusted models for major cardiovascular disease (hazard ratio [HR] 0·90, 95% CI 0·74-1·10, ptrend=0·1301), myocardial infarction (0·99, 0·74-1·31; ptrend=0·2033), stroke (0·92, 0·67-1·25; ptrend=0·7092), cardiovascular mortality (0·73, 0·53-1·02; ptrend=0·0568), non-cardiovascular mortality (0·84, 0·68-1·04; ptrend =0·0038), and total mortality (0·81, 0·68-0·96; ptrend<0·0001). The HR for total mortality was lowest for three to four servings per day (0·78, 95% CI 0·69-0·88) compared with the reference group, with no further apparent decrease in HR with higher consumption. When examined separately, fruit intake was associated with lower risk of cardiovascular, non-cardiovascular, and total mortality, while legume intake was inversely associated with non-cardiovascular death and total mortality (in fully adjusted models). For vegetables, raw vegetable intake was strongly associated with a lower risk of total mortality, whereas cooked vegetable intake showed a modest benefit against mortality. INTERPRETATION: Higher fruit, vegetable, and legume consumption was associated with a lower risk of non-cardiovascular, and total mortality. Benefits appear to be maximum for both non-cardiovascular mortality and total mortality at three to four servings per day (equivalent to 375-500 g/day). FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).

Thickness dependent Raman spectra and interfacial interaction between Ag and epitaxial graphene on 6H-SiC(0001).

Graphene as the thinnest material has an extremely large specific surface area, and thus the physical properties of graphene based devices should be sensitively dependent on the contacted metals. Moreover, the interfacial interaction between graphene and metals is complicated and it is difficult to probe. In this paper, epitaxial graphene is prepared by thermal decomposition of 6H-SiC(0001), and then Ag is deposited on it. It is found that the morphology and distribution of Ag particles on graphene domains are independent of the graphene thickness. The Ag particles induce the surface enhanced Raman scattering (SERS) effect and the doping effect in epitaxial graphene. The enhancement factor of SERS as well as the splitting of the G band and the shift of the 2D band decreases with increasing graphene thickness, which can be ascribed to the weakened interaction between Ag and EG. This is confirmed by the charge transfer between the Ag atom and epitaxial graphene on 6H-SiC predicted by first-principles calculations. The results are helpful to the design and development of graphene-based composites and devices.

Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.

BACKGROUND: Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke. METHODS: We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals. FINDINGS: Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001). INTERPRETATION: Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke. FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network.

Alcohol consumption and cardiovascular disease, cancer, injury, admission to hospital, and mortality: a prospective cohort study.

BACKGROUND: Alcohol consumption is proposed to be the third most important modifiable risk factor for death and disability. However, alcohol consumption has been associated with both benefits and harms, and previous studies were mostly done in high-income countries. We investigated associations between alcohol consumption and outcomes in a prospective cohort of countries at different economic levels in five continents. METHODS: We included information from 12 countries participating in the Prospective Urban Rural Epidemiological (PURE) study, a prospective cohort study of individuals aged 35-70 years. We used Cox proportional hazards regression to study associations with mortality (n=2723), cardiovascular disease (n=2742), myocardial infarction (n=979), stroke (n=817), alcohol-related cancer (n=764), injury (n=824), admission to hospital (n=8786), and for a composite of these outcomes (n=11,963). FINDINGS: We included 114,970 adults, of whom 12,904 (11%) were from high-income countries (HICs), 24,408 (21%) were from upper-middle-income countries (UMICs), 48,845 (43%) were from lower-middle-income countries (LMICs), and 28,813 (25%) were from low-income countries (LICs). Median follow-up was 4.3 years (IQR 3.0-6.0). Current drinking was reported by 36,030 (31%) individuals, and was associated with reduced myocardial infarction (hazard ratio [HR] 0.76 [95% CI 0.63-0.93]), but increased alcohol-related cancers (HR 1.51 [1.22-1.89]) and injury (HR 1.29 [1.04-1.61]). High intake was associated with increased mortality (HR 1.31 [1.04-1.66]). Compared with never drinkers, we identified significantly reduced hazards for the composite outcome for current drinkers in HICs and UMICs (HR 0.84 [0.77-0.92]), but not in LMICs and LICs, for which we identified no reductions in this outcome (HR 1.07 [0.95-1.21]; pinteraction<0.0001). INTERPRETATION: Current alcohol consumption had differing associations by clinical outcome, and differing associations by income region. However, we identified sufficient commonalities to support global health strategies and national initiatives to reduce harmful alcohol use. FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.

Complete genome sequence and comparative genome analysis of a new special Yersinia enterocolitica.

Yersinia enterocolitica is the most diverse species among the Yersinia genera and shows more polymorphism, especially for the non-pathogenic strains. Individual non-pathogenic Y. enterocolitica strains are wrongly identified because of atypical phenotypes. In this study, we isolated an unusual Y. enterocolitica strain LC20 from Rattus norvegicus. The strain did not utilize urea and could not be classified as the biotype. API 20E identified Escherichia coli; however, it grew well at 25 °C, but E. coli grew well at 37 °C. We analyzed the genome of LC20 and found the whole chromosome of LC20 was collinear with Y. enterocolitica 8081, and the urease gene did not exist on the genome which is consistent with the result of API 20E. Also, the 16 S and 23 SrRNA gene of LC20 lay on a branch of Y. enterocolitica. Furthermore, the core-based and pan-based phylogenetic trees showed that LC20 was classified into the Y. enterocolitica cluster. Two plasmids (80 and 50 k) from LC20 shared low genetic homology with pYV from the Yersinia genus, one was an ancestral Yersinia plasmid and the other was novel encoding a number of transposases. Some pathogenic and non-pathogenic Y. enterocolitica-specific genes coexisted in LC20. Thus, although it could not be classified into any Y. enterocolitica biotype due to its special biochemical metabolism, we concluded the LC20 was a Y. enterocolitica strain because its genome was similar to other Y. enterocolitica and it might be a strain with many mutations and combinations emerging in the processes of its evolution.

[Risk assessments and control strategies of plague in five key surveillance counties, Zhejiang province].

OBJECTIVE: To analyze the epidemiology data on plague in five counties in Zhejiang province and to evaluate the risk of plague in theses areas. METHODS: We selected five monitoring stations as a risk assessment (Qingyuan county, Longquan city, Yiwu city, Wencheng county, and Ruian city) in Zhejiang province where the plague epidemic more serious in the history. At least one constant site and 1-4 variable sites where plague occurred in history were selected for monitoring. We collected the five counties (cities) surveillance data of indoor rat density, indoor Rattus flavipectus density, the Xenopsylla cheopis index of rat, the Xenopsylla cheopis index of Rattus flavipectus in 1995-2014. Isolation of Yersinia pestis was conducted among 171,201 liver samples and F1 antibody were detected among 228,775 serum samples. Risk matrix, Borda count method, and Delphi approach were conducted to assess risk of the plague of five counties (cities) in Zhejiang province. RESULTS: Indoor rat density in Qingyuan county, Longquan city, Yiwu city, Wencheng county, Ruian city was 1.58%-5.50%, 1.13%-9.76%, 0.56%-3.67%, 2.83%-16.08%, 7.16%-15.96%, respectively; Indoor Rattus flavipectus density of five counties (cities) was 0.08%-2.23%, 0-2.02%, 0-0.54%, 0.71%-5.58%, 0.55%-4.92%, respectively. The Xenopsylla cheopis index of rat in Qingyuan county and Wencheng county was 0.011-0.500 and 0.015-0.227, respectively; The Xenopsylla cheopis index of Rattus flavipectus of Qingyuan county and Wencheng county was 0.119-3.412 and 0.100-1.430, respectively; Ruian City and Yiwu city cannot collected Xenopsylla cheopis, Long quan city only collected the Xenopsylla cheopis index of rat in the five years. Yersinia pestis were not isolated in five counties (cities).There were 3 Apodemus agrarius samples positive of plague F1 antibody test, in Longquan city and Yiwu city in 2005. Borda count method to assess the Longquan city, Yiwu (Borda point were both 321) plague risk was higher than three other regions; Delphi approach to evaluation five counties (cities) belong to the plague had a lower risk areas, according to the level of risk score (Pf) Longquan city and Yiwu (Pf was 0.314, 0.292, respectively) plague risk were higher than three other regions (Pf were all 0.292). CONCLUSION: The main host and media were lower in five key plague surveillance counties (cities) of Zhejiang province; The result of Borda count method and Delphi approach for risk assessment indicated that endogenous plague recrudescence was at lower level, but Longquan city and Yiwu city risk were higher than other counties (cities).

[Identification of Trypanosoma Species in Rattus flavipectus and R. losea using Microscopy and PCR Method].

OBJECTIVE: To identify two suspected Trypanosoma species in Rattus found in Zhejiang Province using microscopy and PCR method. METHODS: Blood samples were collected from Rattus losea and R. flavipectus. Blood smears were prepared, and observed under microscope. The morphological indices of trypanosomes were measured and calculated. The genomic DNA was extracted from the trypanosomes, and the specific fragment of Trypanosoma 18S rRNA gene was amplified using PCR. The products were further sequenced and submitted to GenBank. Blast analysis was performed on line in NCBI. RESULTS: Blood samples from Ratts flavipectus and R. losea were collected from Lucheng District and Wencheng County of Wenzhou, respectively. The parasites from R. losea and R. flavipectus were found to possess the characteristic features of Trypanosoma species, such as nucleus, free flagellum, and kinetoplast, etc. The body length was 27.50 µm and 23.80 µm, and the free flagellum length was 9.60 im and 9.20 jim, respectively. The nucleus index was 0.74 and 1.05, the kinetoplast Index was 1.40 and 1.57, respectively. Based on the morphological characteristics and host specificity, the parasites from R. losea and R. flavipectus were identified as Herpetosoma species, mainly found in rodents. The amplified products were about 700 bp by 18S rRNA gene PCR with the DNA isolated from the trypanosomes. The products were further sequenced, and the resulting sequences were submitted to GenBank with assession numbers of KP098535 (from R. losea) and KP098536 (from R. flavipectus). Blast analysis showed that KP098535 was completely homologous with the sequences from Herpetosoma subgenus (AY491765.1, AY491764.1, and AJ223568.1), and KP098536 was completely homologous with Trypanosoma lewisi (AB242273.1, AJ009156.1). CONCLUSION: The Trypanosoma species found from Rattus flavipectus is Trypanosoma lewisi, and the other one belongs to Herpetosoma subgenus, which may be named as Trypanosoma lewisi-like trypanosome.