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Fulltext Fabrication of a Multiplexed Artificial Cellular MicroEnvironment Array

Mashimo Y, Yoshioka M, Tokunaga Y, Fockenberg C, Terada S, Koyama Y, et al.

J Vis Exp, 2018 09 07.
PMID: 30247461 DOI: 10.3791/57377

Cellular microenvironments consist of a variety of cues, such as growth factors, extracellular matrices, and intercellular interactions. These cues are well orchestrated and are crucial in regulating cell functions in a living system. Although a number of researchers have attempted to investigate the correlation between environmental factors and desired cellular functions, much remains unknown. This is largely due to the lack of a proper methodology to mimic such environmental cues in vitro, and simultaneously test different environmental cues on cells. Here, we report an integrated platform of microfluidic channels and a nanofiber array, followed by high-content single-cell analysis, to examine stem cell phenotypes altered by distinct environmental factors. To demonstrate the application of this platform, this study focuses on the phenotypes of self-renewing human pluripotent stem cells (hPSCs). Here, we present the preparation procedures for a nanofiber array and the microfluidic structure in the fabrication of a Multiplexed Artificial Cellular MicroEnvironment (MACME) array. Moreover, overall steps of the single-cell profiling, cell staining with multiple fluorescent markers, multiple fluorescence imaging, and statistical analyses, are described.
Mechanism behind the Controlled Generation of Liquid Metal Nanoparticles by Mechanical Agitation

Nor-Azman NA, Ghasemian MB, Fuchs R, Liu L, Widjajana MS, Yu R, et al.

ACS Nano, 2024 Apr 15.
PMID: 38620061 DOI: 10.1021/acsnano.3c12638

The size-controlled synthesis of liquid metal nanoparticles is necessary in a variety of applications. Sonication is a common method for breaking down bulk liquid metals into small particles, yet the influence of critical factors such as liquid metal composition has remained elusive. Our study employs high-speed imaging to unravel the mechanism of liquid metal particle formation during mechanical agitation. Gallium-based liquid metals, with and without secondary metals of bismuth, indium, and tin, are analyzed to observe the effect of cavitation and surface eruption during sonication and particle release. The impact of the secondary metal inclusion is investigated on liquid metals' surface tension, solution turbidity, and size distribution of the generated particles. Our work evidences that there is an inverse relationship between the surface tension and the ability of liquid metals to be broken down by sonication. We show that even for 0.22 at. % of bismuth in gallium, the surface tension is significantly decreased from 558 to 417 mN/m (measured in Milli-Q water), resulting in an enhanced particle generation rate: 3.6 times increase in turbidity and ∼43% reduction in the size of particles for bismuth in gallium liquid alloy compared to liquid gallium for the same sonication duration. The effect of particles' size on the photocatalysis of the annealed particles is also presented to show the applicability of the process in a proof-of-concept demonstration. This work contributes to a broader understanding of the synthesis of nanoparticles, with controlled size and characteristics, via mechanical agitation of liquid metals for diverse applications.
Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study

O'Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, et al.

Lancet, 2016 Aug 20;388(10046):761-75.
PMID: 27431356 DOI: 10.1016/S0140-6736(16)30506-2

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.
Fulltext Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case-control study

Wang X, Liu X, O'Donnell MJ, McQueen M, Sniderman A, Pare G, et al.

EClinicalMedicine, 2024 Apr;70:102515.
PMID: 38516107 DOI: 10.1016/j.eclinm.2024.102515

BACKGROUND: Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels.
METHODS: The INTERSTROKE study is a case-control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined).
FINDINGS: Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46-1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61-2.11) than ICH (OR 1.19 95% CI 1.00-1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24-4.10) and PAR (18.6%, 15.1-22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63-2.87) and undetermined cause (OR 1.97, 95% CI 1.55-2.50). Both filtered (OR 1.73, 95% CI 1.50-1.99) and non-filtered (OR 2.59, 95% CI 1.79-3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69-2.27), ischemic stroke (OR 1.89, 95% CI 1.59-2.24) and ICH (OR 2.00, 95% CI 1.60-2.50).
INTERPRETATION: There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke.
FUNDING: The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.
Detection of microRNA-335-5p on an Interdigitated Electrode Surface for Determination of the Severity of Abdominal Aortic Aneurysms

Lu B, Liu L, Wang J, Chen Y, Li Z, Gopinath SCB, et al.

Nanoscale Res Lett, 2020 May 11;15(1):105.
PMID: 32394009 DOI: 10.1186/s11671-020-03331-y

Abdominal aortic aneurysm (AAA) refers to the enlargement of the lower artery of the abdominal aorta, and identification of an early detection tool is urgently needed for diagnosis. In the current study, an interdigitated electrode (IDE) sensing surface was used to identify miRNA-335-5p, which reflects the formation of AAAs. The uniformity of the silica material was observed by 3D profilometry, and the chemically modified highly conductive surface improved the detection via the I-V mode. The targeted miRNA-335-5p was detected in a dose-dependent manner and based on linear regression and 3σ analyses, the sensitivity was determined to be 1 fM with a biotinylated probe. The high specificity was shown by discriminating the target sequence from noncomplementary and single- and triple-mismatched sequences. These outputs demonstrated the high-performance detection of miRNA-335-5p with good reproducibility for determination of the severity of AAA.
Association of circulating leptin and adiponectin levels with colorectal cancer risk: A systematic review and meta-analysis of case-control studies

Wang Y, Li J, Fu X, Li J, Liu L, Alkohlani A, et al.

Cancer Epidemiol, 2021 08;73:101958.
PMID: 34020315 DOI: 10.1016/j.canep.2021.101958

PURPOSE: Leptin and adiponectin are adipokines which have been commonly implicated in carcinogenesis. As such, many studies have investigated the association of circulating leptin and adiponectin levels with colorectal cancer (CRC) risk. However, the results remained inconsistent.
METHODS: In this work, we performed a systematic review and meta-analysis to precisely examine the association between circulating levels of leptin and adiponectin and CRC risk. A systematic literature search was performed in PubMed/MEDLINE, Scopus, Web of Science, and EMBASE databases from inception until October 2020. The pooled effect size was then estimated by calculating the odds ratio (OR).
RESULTS: A total of 23 records (comprising 26 studies) were included in the meta-analysis. The overall analysis found that circulating levels of leptin and adiponectin were not significantly associated with CRC risk (P > 0.05). Interestingly, subgroup analysis revealed that a higher level of adiponectin was significantly associated with an increased CRC risk among overweight individuals (OR = 1.16; 95 % CI: 1.02, 1.32), and a decreased CRC risk among normal weight individuals (OR = 0.76; 95 % CI: 0.62, 0.92). Besides, a higher level of adiponectin was also significantly associated with a decreased risk of CRC in men (OR = 0.76; 95 % CI: 0.59, 0.98).
CONCLUSIONS: In conclusion, circulating leptin level was not associated with CRC risk, but that of adiponectin was associated with CRC risk only in specific subgroups.
Effect of carnosine supplementation on lipid profile, fasting blood glucose, HbA1C and insulin resistance: A systematic review and meta-analysis of long-term randomized controlled trials

Peng W, Mao P, Liu L, Chen K, Zhong Y, Xia W, et al.

Complement Ther Med, 2020 Jan;48:102241.
PMID: 31987255 DOI: 10.1016/j.ctim.2019.102241

OBJECTIVE: Glucose disorders and dyslipidemia are closely associated with obesity and metabolic disease. The purpose of this study was to investigate the effect of Carnosine supplementation on lipid profile, fasting blood glucose, HbA1C and Insulin resistance.
METHOD: MEDLINE/PubMed, Scopus and Web of sciences were investigated to identify relevant articles up to June 2019. The search strategy combined the Medical Subject Heading and Title and/or abstract keywords. The combined effect sizes were calculated as weight mean difference (WMD) using the random-effects model. Between study heterogeneity was evaluated by the Cochran's Q test and I2.
RESULTS: Four RCTs studies investigated Carnosine use versus any control for at least 2 weeks were identified and analyzed. Overall results from the random-effects model on included studies, with 184 participants, indicated that carnosine intervention reduced HbA1C levels in intervention vs control groups (WMD: -0.92 %, 95 % CI: -1.20, -0.63, I2:69 %). Four studies, including a total of 183 participants, reported TG changes as an outcome measure variable, but combined results did not show significant reduction in this outcome (WMD: -14.46 mg/dl, 95 % CI: -29.11, 0.19, I2:94 %). Furthermore, combined results did not show any significant change in HOMA-IR, Cholesterol, fasting blood sugar, or HDL-C.
CONCLUSION: Carnosine supplementation results in a decrease in HbA1C, but elicits no effect on HOMA-IR, Cholesterol, fasting blood sugar, TG and HDL-C. Future studies with a larger sample sizes, varied doses of carnosine, and population-specific sub-groups are warranted to confirm, and enhance, the veracity of our findings.
Fulltext Contribution of IL-33/ILC2-mediated Th2 cytokines during the progression of minimal change disease

Liu C, Liu L, Huang Y, Shi R, Wu Y, Hakimah Binti Ismail I

Int Immunopharmacol, 2023 Jan;114:109493.
PMID: 36527879 DOI: 10.1016/j.intimp.2022.109493

Minimal change disease (MCD) is a common type of nephrotic syndrome with high recurrence rate. This study aims to explore the impacts of interleukin (IL)-33 in MCD and to discuss its potential mechanism. In adriamycin (ADM) and puromycin aminonucleoside (PAN)-induced MCD rat model, IL-33 was used for treatment. H&E staining was applied for detecting histological changes. Critical proteins were examined by western blot. Corresponding commercial kits tested oxidative stress- and inflammation-related factors. Cell apoptosis was measured by TUNEL assay. ADM-induced podocyte injury model was establish to mimic MCD in vitro. Cell proliferation and apoptosis were detected by CCK-8 and TUNEL assays. Finally, podocyte was stimulated by innate lymphoid type-2 cells-secreted Th2 cytokines (ILC2s: IL-13 and IL-5 respectively), with or without incubation with M1 macrophage medium to further explore the immune-regulation of ILC2s behind the inflammatory environment of MCD. It was found that PAN-induced kidney jury, inflammation, oxidative stress and apoptosis were severer than ADM, and IL-33 treatment significantly alleviated the above injuries in PAN and ADM-induced MCD rat model. Moreover, IL-33 reversed the reduced viability and increased oxidative stress and apoptosis in ADM-induced podocyte injury model. Further, the capacities of IL-13 alone in inducing M1/M2 macrophage polarization, apoptosis, inflammation, kidney injury and reducing cell viability are stronger than IL-5. However, IL-13 reversed reduced cell viability and stimulated apoptosis, inflammation, kidney injury mediated by co-incubation with M1-conditioned medium. Collectively, IL-33 might protect against immunologic injury in MCD via mediating ILC2s-secreted IL-13.
Novel Approaches in Primary Cardiovascular Disease Prevention: The HOPE-3 Trial Rationale, Design, and Participants' Baseline Characteristics

Lonn E, Bosch J, Pogue J, Avezum A, Chazova I, Dans A, et al.

Can J Cardiol, 2016 Mar;32(3):311-8.
PMID: 26481083 DOI: 10.1016/j.cjca.2015.07.001

Cholesterol and blood pressure (BP) can be effectively and safely lowered with statin drugs and BP-lowering drugs, reducing major cardiovascular (CV) events by 20%-30% within 5 years in high-risk individuals. However, there are limited data in lower-risk populations. The Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial is evaluating whether cholesterol lowering with a statin drug, BP lowering with low doses of 2 antihypertensive agents, and their combination safely reduce major CV events in individuals at intermediate risk who have had no previous vascular events and have average cholesterol and BP levels.
Fulltext Blood-pressure and cholesterol lowering in persons without cardiovascular disease

Yusuf S, Lonn E, Pais P, Bosch J, López-Jaramillo P, Zhu J, et al.

N Engl J Med, 2016 May 26;374(21):2032-43.
PMID: 27039945 DOI: 10.1056/NEJMoa1600177

BACKGROUND: Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially.
METHODS: In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years.
RESULTS: The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups.
CONCLUSIONS: The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
Note: Malaysia is a study site (Author: Yusoff K)
Fulltext Blood-pressure lowering in intermediate-risk persons without cardiovascular disease

Lonn EM, Bosch J, López-Jaramillo P, Zhu J, Liu L, Pais P, et al.

N Engl J Med, 2016 May 26;374(21):2009-20.
PMID: 27041480 DOI: 10.1056/NEJMoa1600175

BACKGROUND: Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear.
METHODS: In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years.
RESULTS: The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes).
CONCLUSIONS: Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
Note: Malaysia is a study site (Author: Yusoff K)
Fulltext Cholesterol lowering in intermediate-risk persons without cardiovascular disease

Yusuf S, Bosch J, Dagenais G, Zhu J, Xavier D, Liu L, et al.

N Engl J Med, 2016 May 26;374(21):2021-31.
PMID: 27040132 DOI: 10.1056/NEJMoa1600176

BACKGROUND: Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease. Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons. It is unclear whether the benefits of statins can be extended to an intermediate-risk, ethnically diverse population without cardiovascular disease.
METHODS: In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included revascularization, heart failure, and resuscitated cardiac arrest. The median follow-up was 5.6 years.
RESULTS: The overall mean low-density lipoprotein cholesterol level was 26.5% lower in the rosuvastatin group than in the placebo group. The first coprimary outcome occurred in 235 participants (3.7%) in the rosuvastatin group and in 304 participants (4.8%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.64 to 0.91; P=0.002). The results for the second coprimary outcome were consistent with the results for the first (occurring in 277 participants [4.4%] in the rosuvastatin group and in 363 participants [5.7%] in the placebo group; hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P<0.001). The results were also consistent in subgroups defined according to cardiovascular risk at baseline, lipid level, C-reactive protein level, blood pressure, and race or ethnic group. In the rosuvastatin group, there was no excess of diabetes or cancers, but there was an excess of cataract surgery (in 3.8% of the participants, vs. 3.1% in the placebo group; P=0.02) and muscle symptoms (in 5.8% of the participants, vs. 4.7% in the placebo group; P=0.005).
CONCLUSIONS: Treatment with rosuvastatin at a dose of 10 mg per day resulted in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk, ethnically diverse population without cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; HOPE-3 ClinicalTrials.gov number, NCT00468923.).
Note: Malaysia is a study site (Author: Yusoff K)
Fulltext Retaining nurses via organizational support and pay during COVID-19 pandemic: The moderating effect between intrinsic and extrinsic incentives

Pahlevan Sharif S, She L, Liu L, Naghavi N, Lola GK, Sharif Nia H, et al.

Nurs Open, 2023 Jan;10(1):123-134.
PMID: 35906871 DOI: 10.1002/nop2.1286

AIM: There has been growing concern about the nurses' turnover intention as well as life satisfaction during COVID-19 pandemic in Iran. The past research has provided evidence on the effect of organizational support on nurses' job satisfaction and turnover intention. However, little is known about the underlying mechanism behind these associations.
DESIGN: A cross-sectional survey was undertaken.
METHODS: An online survey was conducted in Iran from May to June 2020 through Google Docs Forms. In total, 305 nurses were participated and completed the online survey. Data were analysed using structural equation modelling through (AMOS). This study was checked with the STROBE checklist.
RESULT: The results showed that nurses' perception of organizational support was positively related to their job satisfaction which in turn decreases the turnover intention. Likewise, the job satisfaction partially mediated the relationship between organizational support and nurses' life satisfaction.
Ultrasound and enzyme assisted preparation of novel lactoferrin-cereal phenolic acid conjugates: structural, physicochemical and functional properties

Li Y, Dong L, Liu Y, Chen Q, Wu Z, Liu L, et al.

Food Chem, 2024 Mar 01;435:137572.
PMID: 37778268 DOI: 10.1016/j.foodchem.2023.137572

The effects of covalent binding of protocatechuic acid (PA) and gallic acid (GA) to lactoferrin (LF) on the structure, functional, and antioxidant properties of the protein conjugate were investigated. These protein-phenolic conjugates were produced by laccase cross-linking and ultrasound-assisted free radical grafting, which were characterized using turbidity, particle size, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analyses. Structural changes in conjugates were monitored by endogenous fluorescence spectroscopy, fourier transform infrared spectroscopy (FTIR), and circular dichroism (CD). The antioxidant capacities and pH stability were determined using DPPH, ABTS, FRAP, and potentiometric analysis. The enzymatic cross-linking and free radical grafting yielded LF-PA/GA conjugates with altered hydrodynamic diameter and zeta-potential. Spectroscopic and chromatographic analyses revealed that binding to PA/GA altered the molecular structure of LF, with a decrease in LF isoelectric point post binding to PA/GA, without affecting antioxidant activities. In conclusion, LF-PA/GA conjugates present potential applications in the food industry.
Dissecting Maillard reaction production in fried foods: Formation mechanisms, sensory characteristic attribution, control strategy, and gut homeostasis regulation

Shi B, Guo X, Liu H, Jiang K, Liu L, Yan N, et al.

Food Chem, 2024 Apr 16;438:137994.
PMID: 37984001 DOI: 10.1016/j.foodchem.2023.137994

Foods rich in carbohydrates or fats undergo the Maillard reaction during frying, which promotes the color, flavor and sensory characteristics formation. In the meanwhile, Maillard reaction intermediates and advanced glycation end products (AGEs) have a negative impact on food sensory quality and gut homeostasis. This negative effect can be influenced by food composition and other processing factors. Whole grain products are rich in polyphenols, which can capture carbonyl compounds in Maillard reaction, and reduce the production of AGEs during frying. This review summarizes the Maillard reaction production intermediates and AGEs formation mechanism in fried food and analyzes the factors affecting the sensory formation of food. In the meanwhile, the effects of Maillard reaction intermediates and AGEs on gut homeostasis were summarized. Overall, the innovative processing methods about the Maillard reaction are summarized to optimize the sensory properties of fried foods while minimizing the formation of AGEs.
The binding mechanism of oat phenolic acid to whey protein and its inhibition mechanism against AGEs as revealed using spectroscopy, chromatography and molecular docking

Dong L, Zhang Y, Li Y, Liu Y, Chen Q, Liu L, et al.

Food Funct, 2023 Nov 13;14(22):10221-10231.
PMID: 37916290 DOI: 10.1039/d3fo02474a

Heat sterilization of dairy products can promote the formation of advanced glycation end products (AGEs), protein oxidation products (POPs) and α-dicarbonyl compounds, which have a significant influence on health due to the close association of these products with diabetes complications. In this study, eight oat phenolic acids were first analyzed for their inhibitory effect against AGEs formation. Due to their strong inhibitory effects and structural differences, caffeic acid (CA) and gallic acid (GA) were further selected to assess their anti-glycosylation mechanisms using spectroscopy, chromatography and molecular docking. CA/GA reduced the production of total AGEs and POPs in various bovine milk simulation models and protected whey proteins from structural modifications, oxidation, and cross-linking. Comparative analyses showed a structure-effect relationship between CA/GA and AGEs inhibition. Oat phenolic acids against AGEs and POPs might be related to the unique bonding of key amino acid residues in whey proteins, the inhibitory role of early fructosamine and the trapping of reactive α-dicarbonyl groups to form adducts. In conclusion, oat phenolic acids might present a promising dietary strategy to alleviate AGEs production and glycation of proteins in dairy products upon storage.
Fulltext Editorial: Changes in food functional components during innovative processing technologies and delivery systems, digestion, and metabolism

Liu L, Wang J, Deng Z

Front Nutr, 2023;10:1200010.
PMID: 37324733 DOI: 10.3389/fnut.2023.1200010
Fulltext Widespread ancient whole-genome duplications in Malpighiales coincide with Eocene global climatic upheaval

Cai L, Xi Z, Amorim AM, Sugumaran M, Rest JS, Liu L, et al.

New Phytol, 2019 Jan;221(1):565-576.
PMID: 30030969 DOI: 10.1111/nph.15357

Whole-genome duplications (WGDs) are widespread and prevalent in vascular plants and frequently coincide with major episodes of global and climatic upheaval, including the mass extinction at the Cretaceous-Tertiary boundary (c. 65 Ma) and during more recent periods of global aridification in the Miocene (c. 10-5 Ma). Here, we explore WGDs in the diverse flowering plant clade Malpighiales. Using transcriptomes and complete genomes from 42 species, we applied a multipronged phylogenomic pipeline to identify, locate, and determine the age of WGDs in Malpighiales using three means of inference: distributions of synonymous substitutions per synonymous site (Ks ) among paralogs, phylogenomic (gene tree) reconciliation, and a likelihood-based gene-count method. We conservatively identify 22 ancient WGDs, widely distributed across Malpighiales subclades. Importantly, these events are clustered around the Eocene-Paleocene transition (c. 54 Ma), during which time the planet was warmer and wetter than any period in the Cenozoic. These results establish that the Eocene Climatic Optimum likely represents a previously unrecognized period of prolific WGDs in plants, and lends further support to the hypothesis that polyploidization promotes adaptation and enhances plant survival during episodes of global change, especially for tropical organisms like Malpighiales, which have tight thermal tolerances.
Fulltext The Influence of Entrepreneurial Characteristics on the Performance of Tourism Vlogger Entrepreneurs

Xie Q, Liu L, Malik H, Chupradit S, Chupradit PW

Front Psychol, 2021;12:725545.
PMID: 34434154 DOI: 10.3389/fpsyg.2021.725545

The current Internet revolution has changed the entrepreneurial opportunities and trends. This study explores the relationship between entrepreneurial characteristics (e.g., innovation, leadership, planning, and sociability) and the performance of entrepreneurial vloggers in India. In addition, this study considers the mediating effect of entrepreneurial intentions. This study is cross-sectional, and it considered 128 entrepreneurial vloggers for the analysis. The SmartPLS application was used to estimate the structural equation modeling (SEM) analysis for the estimation of reliability and validity along with the path relationship. The findings are more important as the entrepreneurial characteristics can meaningfully predict the performance of entrepreneurial vloggers in a positive direction. Moreover, the relationship between entrepreneurial characteristics and the performance of entrepreneurs is partially mediated by entrepreneurial intentions. These findings have important implications for vloggers in Indian or other countries with similar nature. This study has also put some future research directions at the end.
Fulltext Enterococcus faecalis Endophthalmitis: Clinical Settings, Antibiotic Susceptibility, and Management Outcomes

Chen KJ, Lai CC, Chen HC, Chong YJ, Sun MH, Chen YP, et al.

Microorganisms, 2021 Apr 24;9(5).
PMID: 33923356 DOI: 10.3390/microorganisms9050918

Enterococcus faecalis is known to cause severe acute endophthalmitis and often leads to poor visual outcomes in most ophthalmic infections. This retrospective study is to report the clinical settings, antimicrobial susceptibility patterns, and visual outcome of E. faecalis endophthalmitis at a tertiary referral institution in Taoyuan, Taiwan. E. faecalis endophthalmitis was diagnosed in 37 eyes of 37 patients. Post-cataract surgery was the most common cause (n = 27, 73%), followed by bleb-associated (n = 3, 8%), endogenous (n = 2, 5%), corneal ulcer-related (n = 2, 5%), post-vitrectomy (n = 1, 3%), post-pterygium excision (n = 1, 3%), and trauma (n = 1, 3%). Visual acuities upon presentation ranged from counting fingers to no light perception. Pars plana vitrectomy with intravitreal antibiotics were performed in 23 eyes (76%) as primary or secondary treatment. All isolates (37/37, 100%) were sensitive to vancomycin, penicillin, ampicillin, and teicoplanin. Six of 22 eyes (27%) were resistant to high-level gentamicin (minimum inhibitory concentration > 500 mg/L). Final visual acuities were better than 20/400 in 11 eyes (30%), 5/200 to hand motions in 4 eyes (11%), and light perception to no light perception in 22 eyes (59%). Three eyes were treated with evisceration. Compared with non-cataract subgroups, the post-cataract subgroup showed a significant difference of better visual prognosis (p = 0.016).

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