Cell refractive index is a key biophysical parameter, which has been extensively studied. It is correlated with other cell biophysical properties including mechanical, electrical and optical ...properties, and not only represents the intracellular mass and concentration of a cell, but also provides important insight for various biological models. Measurement techniques developed earlier only measure the effective refractive index of a cell or a cell suspension, providing only limited information on cell refractive index and hence hindering its in-depth analysis and correlation. Recently, the emergence of microfluidic, photonic and imaging technologies has enabled the manipulation of a single cell and the 3D refractive index of a single cell down to sub-micron resolution, providing powerful tools to study cells based on refractive index. In this review, we provide an overview of cell refractive index models and measurement techniques including microfluidic chip-based techniques for the last 50 years, present the applications and significance of cell refractive index in cell biology, hematology, and pathology, and discuss future research trends in the field, including 3D imaging methods, integration with microfluidics and potential applications in new and breakthrough research areas.
Cell refractive index is an important biophysical parameter, which provides new biological and biomedical insight for disease diagnosis and cell biology.
To investigate age-associated changes in airway microbiome composition and their relationships with lung function and arterial stiffness among genetically matched young and elderly pairs.
Twenty-four ...genetically linked family pairs comprised of younger (≤40 years) and older (≥60 years) healthy participants were recruited (Total n = 48). Lung function and arterial stiffness (carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx)) were assessed. Sputum samples were collected for targeted 16S rRNA gene amplicon sequencing and correlations between microbiome composition, lung function and arterial stiffness were investigated.
Elderly participants exhibited reductions in lung function (FEV1 (p<0.001), FVC (p<0.001) and percentage FEV1/FVC (p = 0.003)) and a 1.3-3.9-fold increase in arterial stiffness (p<0.001) relative to genetically related younger adults. Elderly adults had a higher relative abundance of Firmicutes (p = 0.035) and lower relative abundance of Proteobacteria (p = 0.014), including specific genera Haemophilus (p = 0.024) and Lautropia (p = 0.020) which were enriched in the younger adults. Alpha diversity was comparable between young and elderly pairs (p>0.05) but was inversely associated with lung function (FEV1%Predicted and FVC %Predicted) in the young (p = 0.006 and p = 0.003) though not the elderly (p = 0.481 and p = 0.696). Conversely, alpha diversity was negatively associated with PWV in the elderly (p = 0.01) but not the young (p = 0.569). Specifically, phylum Firmicutes including the genus Gemella were correlated with lung function (FVC %Predicted) in the young group (p = 0.047 and p = 0.040), while Fusobacteria and Leptotrichia were associated with arterial stiffness (PWV) in the elderly (both p = 0.004).
Ageing is associated with increased Firmicutes and decreased Proteobacteria representation in the airway microbiome among a healthy Asian cohort. The diversity and composition of the airway microbiome is independently associated with lung function and arterial stiffness in the young and elderly groups respectively. This suggests differential microbial associations with these phenotypes at specific stages of life with potential prognostic implications.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Porous molecular solids are promising materials for gas storage and gas separation applications. However, given the relative dearth of structural information concerning these materials, additional ...studies are vital for further understanding their properties and developing design parameters for their optimization. Here, we examine a series of isostructural cuboctahedral, paddlewheel-based coordination cages, M24(tBu-bdc)24 (M = Cr, Mo, Ru; tBu-bdc2– = 5-tert-butylisophthalate), for high-pressure methane storage. As the decrease in crystallinity upon activation of these porous molecular materials precludes diffraction studies, we turn to a related class of pillared coordination cage-based metal–organic frameworks, M24(Me-bdc)24(dabco)6 (M = Fe, Co; Me-bdc2– = 5-methylisophthalate; dabco = 1,4-diazabicyclo2.2.2octane) for neutron diffraction studies. The five porous materials display BET surface areas from 1057–1937 m2/g and total methane uptake capacities of up to 143 cm3(STP)/cm3. Both the porous cages and cage-based frameworks display methane adsorption enthalpies of −15 to −22 kJ/mol. Also supported by molecular modeling, neutron diffraction studies indicate that the triangular windows of the cage are favorable methane adsorption sites with CD4–arene interactions between 3.7 and 4.1 Å. At both low and high loadings, two additional methane adsorption sites on the exterior surface of the cage are apparent for a total of 56 adsorption sites per cage. These results show that M24L24 cages are competent gas storage materials and further adsorption sites may be optimized by judicious ligand functionalization to control extracage pore space.
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IJS, KILJ, NUK, PNG, UL, UM
Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions ...in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer's theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.
INTRODUCTIONAging increases the prevalence of glucose intolerance, but exercise improves glucose homeostasis. The fibroblast growth factor 21 (FGF21)–adiponectin axis helps regulate glucose ...metabolism. However, the role of FGF21 in mediating glucose metabolism with aging and exercise remains unknown.
PURPOSEThis study examined whether FGF21 responses to a glucose challenge are associated with habitual exercise, aging and glucose regulation.
METHODSEighty age- and sex-matched healthy individuals were assigned to young sedentary and active (≤36 yr, n = 20 each group) and older sedentary and active (≥45 yr, n = 20 each group) groups. Fasted and postprandial blood glucose concentration and plasma concentration of insulin, FGF21, and adiponectin were determined during an oral glucose tolerance test (OGTT).
RESULTSDuring the OGTT, glucose concentrations were 9% higher (P = 0.008) and FGF21 concentrations were 58% higher (P = 0.014) in the older than the younger group, independent of activity status. Active participants had 40% lower insulin concentration and 53% lower FGF21 concentration than sedentary participants, independent of age (all P < 0.001). Adiponectin concentration during the OGTT did not differ by age (P = 0.448) or activity status (P = 0.611). Within the younger group, postprandial glucose, insulin and FGF21 concentrations during the OGTT were lower in active than in sedentary participants. In the older group, only postprandial insulin and FGF21 concentrations were lower in active participants.
CONCLUSIONSFGF21, but not adiponectin, response during the OGTT is higher in older than younger adults and lower in active than sedentary individuals. Exercise-associated reduction in OGTT glucose concentrations was observed in younger but not older adults.
Sleep problems are prevalent during adolescence, but parents may be able to support adolescents to sleep better. A systematic search of records from six databases from inception up to November 2019, ...identified 103 peer-reviewed publications that examined behaviourally and cognitively modifiable parental factors associated with sleep in adolescents aged 12–18 years. Although included studies were largely cross-sectional and heterogeneous, with heavy reliance on self-reported measures, associations with sound, convergent levels of evidence were found for: 1) parental rule-setting for bedtimes and parent sleep behaviours with longer sleep duration in adolescents; 2) healthy parent sleep and family functioning with better adolescent sleep quality; and 3) parental warmth with better adolescent daytime functioning. Effect sizes were in the small to moderate range. The identified parental factors are recommended targets for inclusion in parenting programs to support adolescent sleep, however, would require validation in intervention studies. Opportunities for research are outlined for the identified parental factors, sleep domains with limited evidence, and better understanding the mechanisms or possible moderators in the associations between parental factors and sleep outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The term hydrocolloid generally refers to substances that form gels or provide viscous dispersion in the presence of water. Alginate, agar, and carrageenan are three commercially valuable ...hydrocolloids derived from certain brown and red seaweed and each has their distinct physicochemical properties (i.e. functional and bioactive). Various applications of these seaweed hydrocolloids as thickeners, stabilizers, coagulants and salves (in the wound and burn dressings) and materials to produce bio-medical impressions in the food, pharmaceutical, and biotechnology industries are highlighted in this review. Although the existing industrial methods of extraction for these seaweed hydrocolloids are well-established, still growing demand has exposed certain limitations of those methods, notably efficiency and product consistency. In order to achieve targeted hydrocolloids for specific purposes and functionalities, some novel and green extraction methods have also been proposed and discussed. Microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), enzyme-assisted extraction (EAE), supercritical fluid extraction (SFE), pressurized solvent extractions (PSE), reactive extrusion and photo-bleaching process are selectively presented as highly promising candidates that can avoid the use of chemicals and provide novel means of access to seaweed hydrocolloids with both economic and environmental benefits. However, this review does not provide the 'best' method or procedure as many are still under development. Hence, the review gives 'food for thought'as to new processes which might be adopted industrially and concluded that further research is required in order to contribute additional new knowledge and refinement to this field of study.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In this paper, for the first time, an on-chip optofluidic imaging system is innovated to measure the biophysical signatures of single waterborne bacteria, including both their refractive indices and ...morphologies (size and shape), based on immersion refractometry. The key features of the proposed optofluidic imaging platform include (1) multiple sites for single-bacterium trapping, which enable parallel measurements to achieve higher throughput, and (2) a chaotic micromixer, which enables efficient refractive index variation of the surrounding medium. In the experiments, the distinctive refractive index of Echerichia coli, Shigella flexneri and Vibrio cholera are measured with a high precision of 5 × 10(-3) RIU. The developed optofluidic imaging system has high potential not only for building up a database of biophysical signatures of waterborne bacteria, but also for developing single-bacterium detection in treated water that is in real-time, label-free and low cost.
What is the central question of this study?
Fibroblast growth factor 21 (FGF21) plays important therapeutic roles in metabolic diseases but is associated with bone loss, through insulin‐like growth ...factor binding protein 1 (IGFBP1), in animals. However, the effect of the FGF21–IGFBP1 axis on age‐related bone loss has not been explored in humans.
What is the main finding and its importance?
Using ‘genetically linked’ parent and child family pairs, we show that the FGF21 concentration, but not the IGFBP1 concentration, is higher in older than in younger adults. Our results suggest that age‐associated decline in bone mineral density is associated with FGF21 and increased bone turnover but not likely to involve IGFBP1 in healthy humans.
Bone fragility increases with age. The fibroblast growth factor 21 (FGF21)–insulin‐like growth factor binding protein 1 (IGFBP1) axis regulates bone loss in animals. However, the role of FGF21 in mediating age‐associated bone fragility in humans remains unknown. The purpose of this study was to explore the FGF21‐regulatory axis in bone turnover and the age‐related decline in bone mineral density (BMD). Twenty ‘genetically linked’ family (parent and child) pairs were recruited. Younger adults were 22–39 years old and older adults 60–71 years old. The BMD and serum concentrations of FGF21, IGFBP1, receptor activator of nuclear factor‐κB ligand (RANKL), tartrate‐resistant acid phosphatase 5b (TRAP5b) and bone‐specific alkaline phosphatase (BAP) were measured. Older adults had 10–18% lower BMD at the hip and spine (P < 0.008) and a twofold higher FGF21 concentration (P < 0.001). The IGFBP1 concentration was similar in younger and older adults (P = 0.961). The RANKL concentration was 44% lower (P = 0.006), whereas TRAP5b and BAP concentrations were 36 and 31% higher (P = 0.01 and P = 0.004), respectively, in older adults than in younger adults. Adjusting for sex did not affect these results. The FGF21 concentration was negatively correlated with BMD at the spine (r = −0.460, P = 0.003), but not with the IGFBP1 concentration (r = −0.144, P = 0.374). The IGFBP1 concentration was not correlated with BMD at the hip or spine (all P > 0.05). In humans, FGF21 might be involved in the age‐associated decline in BMD, especially at the spine, through increased bone turnover. IGFBP1 is unlikely to be the downstream effector of FGF21 in driving the age‐associated decline in BMD and in RANKL‐associated osteoclast differentiation.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
ABSTRACT
The human amylase gene locus at chromosome 1p21.1 is structurally complex. This region contains two pancreatic amylase genes, AMY2B, AMY2A, and a salivary gene AMY1. The AMY1 gene harbors ...extensive copy number variation (CNV), and recent studies have implicated this variation in adaptation to starch‐rich diets and in association to obesity for European and Asian populations. In this study, we showed that by combining quantitative PCR and digital PCR, coupled with careful experimental design and calibration, we can improve the resolution of genotyping CNV with high copy numbers (CNs). In two East Asian populations of Chinese and Malay ethnicity studied, we observed a unique non‐normal distribution of AMY1 diploid CN genotypes with even:odd CNs ratio of 4.5 (3.3–4.7), and an association between the common AMY2A CN = 2 genotype and odd CNs of AMY1, that could be explained by the underlying haplotypic structure. In two further case–control cohorts (n = 932 and 145, for Chinese and Malays, respectively), we did not observe the previously reported association between AMY1 and obesity or body mass index. Improved methods for accurately genotyping multiallelic CNV loci and understanding the haplotype complexity at the AMY1 locus are necessary for population genetics and association studies.
The salivary amylase gene AMY1 harbours extensive copy number (CN) variation (CNV). By improving the resolution of CNV genotyping using quantitative PCR and digital PCR we discovered an unusual even:odd CN ratio in two East Asian populations (Chinese and Malay) studied, caused by the underlying haplotypic structure. With this high resolution CN genotyping method, we could not replicate the previously reported association between AMY1 and obesity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK