Nonspherical ultrasound microbubbles.

Surface tension provides microbubbles (MB) with a perfect spherical shape. Here, we demonstrate that MB can be engineered to be nonspherical, endowing them with unique features for biomedical applications. Anisotropic MB were generated via one-dimensionally stretching spherical poly(butyl cyanoacrylate) MB above their glass transition temperature. Compared to their spherical counterparts, nonspherical polymeric MB displayed superior performance in multiple ways, including i) increased margination behavior in blood vessel-like flow chambers, ii) reduced macrophage uptake in vitro, iii) prolonged circulation time in vivo, and iv) enhanced blood-brain barrier (BBB) permeation in vivo upon combination with transcranial focused ultrasound (FUS). Our studies identify shape as a design parameter in the MB landscape, and they provide a rational and robust framework for further exploring the application of anisotropic MB for ultrasound-enhanced drug delivery and imaging applications.

Impact of cesarean section on metabolic syndrome components in offspring rats.

INTRODUCTION: Epidemiological evidence suggests an association between CS and offspring metabolic syndrome (MetS), but whether a causal relationship exists is unknown. METHODS: In this study, timed-mated Wistar rat dams were randomly assigned to cesarean section (CS), vaginal delivery (VD), and surrogate groups. The offspring from both CS and VD groups were reared by surrogate dams until weaning, and weaned male offspring from both groups were randomly assigned to receive normal diet (ND) or high-fat/high-fructose diet (HFF) ad libitum for 39 weeks. RESULTS: By the end of study, CS-ND offspring gained 17.8% more weight than VD-ND offspring, while CS-HFF offspring gained 36.4% more weight than VD-HFF offspring. Compared with VD-ND offspring, CS-ND offspring tended to have increased triglycerides (0.27 mmol/l, 95% CI, 0.05 to 0.50), total cholesterol (0.30 mmol/l, -0.08 to 0.68), and fasting plasma glucose (FPG) (0.30 mmol/l, -0.01 to 0.60); more pronounced differences were observed between CS-HFF and VD-HFF offspring in these indicators (triglyceride, 0.66 mmol/l, 0.35 to 0.97; total cholesterol, 0.46 mmol/l, 0.13 to 0.79; and FPG, 0.55 mmol/l, 0.13 to 0.98). CONCLUSIONS: CS offspring were more prone to adverse metabolic profile and HFF might exacerbate this condition, indicating the association between CS and MetS is likely to be causal. IMPACT: Whether the observed associations between CS and MetS in non-randomized human studies are causally relevant remains undetermined. Compared with vaginally born offspring rats, CS born offspring gained more body weight and tended to have compromised lipid profiles and abnormal insulin sensitivity, suggesting a causal relationship between CS and MetS that may be further amplified by a high-fat/high-fructose diet. Due to the high prevalence of CS births globally, greater clinical consideration must be given to the potential adverse effects of CS, and whether these risks should be made known to patients in clinical practice merits evaluation.

Novel broad-spectrum bacteriophages against Xanthomonas oryzae and their biocontrol potential in rice bacterial diseases.

Bacterial leaf blight (BLB) and bacterial leaf streak (BLS)-caused by Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), respectively-are two major bacterial diseases that threaten the safe production of rice, one of the most important food crops. Bacteriophages are considered potential biocontrol agents against rice bacterial pathogens, due to their host specificity and environmental safety. It is common for BLB and BLS to occur together in fields, which highlights the need for broad-spectrum phages capable of infecting both Xoo and Xoc. In this study, two lytic broad-spectrum phages (pXoo2106 and pXoo2107) that can infect various strains of Xoo and Xoc were assessed. Both phages belong to the class Caudoviricetes and one of them to the family Autographiviridae, while the other belongs to an unclassified family. Two phages alone or combined in a phage cocktail could effectively inhibit Xoo and Xoc growth in vitro. In an in vivo biocontrol experiment, the phage cocktail reduced the total CFU and significantly eased the symptoms caused by Xoo or Xoc. Our results suggest that pXoo2106 and pXoo2107 have a broad-spectrum host range targeting different X. oryzae strains, and have strong biocontrol potential in field applications against both BLB and BLS.

Maternal glycemic status during pregnancy and mid-childhood plasma amino acid profiles: findings from a multi-ethnic Asian birth cohort.

BACKGROUND: Increasing maternal glycaemia across the continuum during pregnancy may predispose offspring to subsequent cardiometabolic risk later in life. However, evidence of long-term impacts of maternal glycemic status on offspring amino acid (AA) profiles is scarce. We aimed to investigate the association between maternal antenatal glycaemia and offspring mid-childhood amino acid (AA) profiles, which are emerging cardiometabolic biomarkers. METHODS: Data were drawn from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study, a multi-ethnic Asian birth cohort. A subset of 422 mother-child dyads from the GUSTO study, who was followed from early pregnancy to mid-childhood, was included. Mothers underwent an oral glucose tolerance test (OGTT) at 26-28 weeks gestation, with fasting and 2-h plasma glucose concentrations measured and gestational diabetes mellitus (GDM) diagnosed per WHO 1999 guidelines. Offspring fasting plasma samples were collected at mean age 6.1 years, from which AA profiles of nine AAs, alanine, glutamine, glycine, histidine, isoleucine, leucine, valine, phenylalanine, and tyrosine were measured. Total branched-chain amino acids (BCAAs) were calculated as the sum of isoleucine, leucine, and valine concentrations. Multi-variable linear regression was used to estimate the association of maternal glycemic status and offspring mid-childhood AA profiles adjusting for maternal age, ethnicity, maternal education, parity, family history of diabetes, ppBMI, child sex, age and BMI z-scores. RESULTS: Approximately 20% of mothers were diagnosed with GDM. Increasing maternal fasting glucose was significantly associated with higher offspring plasma valine and total BCAAs, whereas higher 2-h glucose was significantly associated with higher histidine, isoleucine, valine, and total BCAAs. Offspring born to mothers with GDM had higher valine (standardized mean difference 0.27 SD; 95% CI: 0.01, 0.52), leucine (0.28 SD; 0.02, 0.53), and total BCAAs (0.26 SD; 0.01, 0.52) than their counterparts. Inconsistent associations were found between maternal GDM and other amino acids among offspring during mid-childhood. CONCLUSIONS: Increasing maternal fasting and post-OGTT glucose concentrations at 26-28 weeks gestation were significantly associated with mid-childhood individual and total BCAAs concentrations. The findings suggest that elevated maternal glycaemia throughout pregnancy, especially GDM, may have persistent programming effects on offspring AA metabolism which were strongly associated with adverse cardiometabolic profiles at mid-childhood.

Highly Durable Bidirectional Rotary Triboelectric Nanogenerator with a Self-Lubricating Texture and Self-Adapting Contact Synergy for Wearable Applications.

Sliding-freestanding triboelectric nanogenerators (SF-TENGs) are desirable for application in wearable power sources; however, improving their durability is the primary challenge. Meanwhile, few studies focus on enhancing the service life of tribo-materials, especially from an anti-friction perspective during dry operation. Herein, for the first time, a surface-textured film with self-lubricating property is introduced into the SF-TENG as a tribo-material, which is obtained by the self-assembly of hollow SiO2 microspheres (HSMs) close to a polydimethylsiloxane (PDMS) surface under vacuum conditions. The PDMS/HSMs film with micro-bump topography simultaneously reduces the dynamic coefficient of friction from 1.403 to 0.195 and increases the electrical output of SF-TENG by an order of magnitude. Subsequently, a textured film and self-adapting contact synergized bidirectional rotary TENG (TAB-TENG) is developed, and the superiorities of the soft flat rotator with bidirectional reciprocating rotation are systematically investigated. The obtained TAB-TENG exhibits a remarkable output stability and an outstanding mechanical durability over 350 000 cycles. Furthermore, a smart foot system for stepping energy harvesting and wireless walking states monitoring is realized. This study proposes a pioneering strategy for extending the lifetime of SF-TENGs and advances it toward practical wearable applications.

A Ratiometric Fluorescent Probe Based on RhB Functionalized Tb-MOFs for the Continuous Visual Detection of Fe3+ and AA.

In this study, a red-green dual-emitting fluorescent composite (RhB@MOFs) was constructed by introducing the red-emitting organic fluorescent dye rhodamine B (RhB) into metal-organic frameworks (Tb-MOFs). The sample can be used as a ratiometric fluorescent probe, which not only avoids errors caused by instrument and environmental instability but also has multiple applications in detection. The results indicated that the RhB@MOFs exhibited a turned-off response toward Fe3+ and a turned-on response for the continuous detection of ascorbic acid (AA). This ratiometric fluorescent probe possessed high sensitivity and excellent selectivity in the continuous determination of Fe3+ and AA. It is worth mentioning that remarkable fluorescence change could be clearly observed by the naked eye under a UV lamp, which is more convenient in applications. In addition, the mechanisms of Fe3+- and AA-induced fluorescence quench and recovery are discussed in detail. This ratiometric probe displayed outstanding recognition of heavy metal ions and biomolecules, providing potential applications for water quality monitoring and biomolecule determination.

Does inflammation mediate the association between obesity and hearing status in mid-childhood and mid-life?

BACKGROUND: Obesity is characterized by heightened inflammation, and both phenotypes are associated with hearing loss. We aimed to determine if inflammation mediates the associations between obesity and hearing ability in mid-childhood and mid-life. METHODS: Participants: 1165 11- to 12-year-old children and 1316 parents in the population-based cross-sectional Child Health CheckPoint within the Longitudinal Study of Australian Children. Adiposity measures: Body mass index (BMI) classified as normal, overweight and obesity; waist-to-height ratio (WHtR) classified as <0.5 and ≥0.5; fat mass index. Inflammatory biomarkers: Serum glycoprotein A (GlycA); high-sensitivity C-reactive protein (hsCRP). Audiometry: Composite high Fletcher Index (mean threshold of 1, 2, 4 kHz) in the better ear. ANALYSIS: Causal mediation analysis decomposed a 'total effect' (obesity on hearing status) into 'indirect' effect via a mediator (eg GlycA, hsCRP) and 'direct' effect via other pathways, adjusting for age, sex and socioeconomic position. RESULTS: Compared to adults with BMI within the normal range, those with obesity had hearing thresholds 1.9 dB HL (95% CI 1.0-2.8) higher on the high Fletcher Index; 40% of the total effect was mediated via GlycA (indirect effect: 0.8 dB HL, 95% CI 0.1-1.4). Children with obesity had hearing thresholds 1.3 dB HL (95% CI 0.2-2.5) higher than those with normal BMI, of which 67% (indirect effect: 0.9 dB HL, 95% CI 0.4-1.4) was mediated via GlycA. Similar mediation effects were noted using other adiposity measures. Similar but less marked mediation effects were observed when hsCRP was used as the inflammatory biomarker (6-23% in adults and 23-33% in children). CONCLUSIONS: Inflammation may play an important mediating role in the modest hearing reductions associated with obesity, particularly in children. These findings offer insights into possible mechanisms and early prevention strategies for hearing loss.

Isolation and identification of a new biocontrol bacteria against Salvia miltiorrhiza root rot and optimization of culture conditions for antifungal substance production using response surface methodology.

BACKGROUND: S. miltiorrhiza root rot is a soil-borne disease mainly caused by Fusarium solani and Fusarium oxysporum, which has spread rapidly in China in recent years. To reduce the amount of pesticides to control this plant fungal disease, biological control using endophytic bacteria is a promising method. Many endophytic bacteria show good biocontrol potential against various plant fungal diseases. The aims of this study were to isolate and identify endophytic bacteria with antifungal activity from Salvia miltiorrhiza plant tissue. In order to increase antifungal substances production, the culture conditions of the isolated DS-R5 strain were optimized through response surface methodology. RESULTS: Thirteen endophytic bacteria with antifungal activity against the target pathogenic fungus were successfully screened. The DS-R5 strain that had the strongest antifungal activity was identified based on morphological, physiological and biochemical characteristics, 16S rRNA and gyrB sequence analysis.The results of response surface methodology experiments showed that the optimal values of the three significant factors were as follows: medium volume, 51.0 ml; initial pH, 6.7; fermentation temperature, 33.1 °C. Under these optimal culture conditions, the titer of antifungal substances produced by the DS-R5 strain was 77.6% higher than that under the initial culture conditions. CONCLUSIONS: The antifungal activity of endophytic bacteria from Salvia miltiorrhiza has been demonstrated for the first time, which may benefit future crop quality and production. In addition, response surface methodology can be well applied the optimization of culture conditions for antifungal substance, which lays the foundation for further research on strain DS-R5.

Does an inflammatory diet affect mental well-being in late childhood and mid-life? A cross-sectional study.

Inflammatory diets are increasingly recognised as a modifiable determinant of mental illness. However, there is a dearth of studies in early life and across the full mental well-being spectrum (mental illness to positive well-being) at the population level. This is a critical gap given that inflammatory diet patterns and mental well-being trajectories typically establish by adolescence. We examined the associations of inflammatory diet scores with mental well-being in 11-12-year-olds and mid-life adults. Throughout Australia, 1759 11-12-year-olds (49 % girls) and 1812 parents (88 % mothers) contributed cross-sectional population-based data. Alternate inflammatory diet scores were calculated from a twenty-six-item FFQ, based on the prior literature and prediction of inflammatory markers. Participants reported negatively and positively framed mental well-being via psychosocial health, quality of life and life satisfaction surveys. We used causal inference modelling techniques via generalised linear regression models (mean differences and risk ratios (RR)) to examine how inflammatory diets might influence mental well-being. In children and adults, respectively, a 1 sd higher literature-derived inflammatory diet score conferred between a 44 % (RR 95 % CI 1·2, 1·8) to 57 % (RR 95 % CI 1·3, 2·0) and 54 % (95 % CI 1·2, 2·0) to 86 % (RR 95 % CI 1·4, 2·4) higher risk of being in the worst mental well-being category (i.e. <16th percentile) across outcome measures. Results for inflammation-derived scores were similar. BMI mediated effects (21-39 %) in adults. Inflammatory diet patterns were cross-sectionally associated with mental well-being at age 11-12 years, with similar effects observed in mid-adulthood. Reducing inflammatory dietary components in childhood could improve population-level mental well-being across the life course.

Construction of automated high-throughput screening method for finding efficient 3-ketosteroid 1,2-dehydrogenating strains.

Dehydrogenation reaction at C1(2) positions is typical and representative of industrial production of steroid drugs. Anti-inflammatory activity can be doubled when the nucleus of the anti-inflammatory steroid hormone drug introduces double bonds at the C1(2) positions. Arthrobacter simplex is currently the most widely studied and used strain for C1(2) dehydrogenation. Therefore, breeding Arthrobacter simplex with high-efficiency dehydrogenation ability is of great significance. In order to obtain high-efficiency strains, the research proposed a new screening strategy based on image process technique: firstly, a color reaction between 2,4-dinitrophenylhydrazine (DNPH) and 9α-hydroxyandrost-4-ene-3,17-dione (9α-OH-AD) was established to characterize the dehydrogenation ability of the strain; secondly, the color data of strains mutated by atmospheric and room temperature plasma (ARTP) in the "color reaction" were automated and analyzed for dehydrogenation ability prediction using optimized support vector machine model. Result showed that the prediction accuracy reached as high as 96% in verification experiments. After a series of mutagenesis, including breaking the bottleneck of a single mutation in ARTP, the dominant strain ARLU-146 was finally obtained from 5168 strains. Its initial conversion rate was 0.8059 g/L/h, with a conversion of 94.41% at 24 h, compared to the original strain ASP which increased the transformation rate by more than 10%. By further process optimization, a high conversion (94.34% within 20 h) with high substrate (85 g/L cortisone acetate) was achieved. According to literature research, it is the highest conversion at this substrate concentration. KEY POINTS: • A high-throughput screening method was developed by using image processing and machine learning technique. • "Mutation bottleneck" of single ARTP mutagenesis was surpassed by complex mutagenesis. • A high substrate (85 g/L CA) and high transformation rate craft (94.34% within 20 h) were built.

Genome-Wide Analysis of C2H2 Zinc Finger Gene Family and Its Response to Cold and Drought Stress in Sorghum [Sorghum bicolor (L.) Moench].

C2H2 zinc finger protein (C2H2-ZFP) is one of the most important transcription factor families in higher plants. In this study, a total of 145 C2H2-ZFPs was identified in Sorghum bicolor and randomly distributed on 10 chromosomes. Based on the phylogenetic tree, these zinc finger gene family members were divided into 11 clades, and the gene structure and motif composition of SbC2H2-ZFPs in the same clade were similar. SbC2H2-ZFP members located in the same clade contained similar intron/exon and motif patterns. Thirty-three tandem duplicated SbC2H2-ZFPs and 24 pairs of segmental duplicated genes were identified. Moreover, synteny analysis showed that sorghum had more collinear regions with monocotyledonous plants such as maize and rice than did dicotyledons such as soybean and Arabidopsis. Furthermore, we used quantitative RT-PCR (qRT-PCR) to analyze the expression of C2H2-ZFPs in different organs and demonstrated that the genes responded to cold and drought. For example, Sobic.008G088842 might be activated by cold but is inhibited in drought in the stems and leaves. This work not only revealed an important expanded C2H2-ZFP gene family in Sorghum bicolor but also provides a research basis for determining the role of C2H2-ZFPs in sorghum development and abiotic stress resistance.

Spraying high concentrations of chelated zinc enhances zinc biofortification in wheat grain.

BACKGROUND: Foliar application of highly concentrated ZnSO4 fertilizer improves Zn biofortification in wheat grains. However, excess ZnSO4 ·7H2 O concentration (≥5 g kg-1 , w v-1 ) has been associated with leaf burn and yield loss, necessitating Zn sources with a high threshold concentration. The aim of this study, based on a 2 year field experiment conducted on wheat cultivated in acidic and alkaline soil, was to identify a suitable Zn formulation with a high Zn concentration or efficient adjuvant to achieve optimal Zn biofortification levels without compromising agronomic performance. RESULTS: There was a continued increase in the Zn concentration in wheat grains and a decrease in grain yield with an increase in the concentration of the Zn foliar sprays in both soil types examined. Wheats treated with chelated Zn foliar sprays - Zn glycine chelate (ZnGly) and Zn-ethylenediaminetetraacetic acid (ZnEDTA) - had less foliar injury than those treated with unchelated Zn fertilizers. Furthermore, irrespective of wheat cultivars and soil types, ZnEDTA applied to wheat at a concentration of 10 g kg-1 achieved the highest grain Zn concentration without negatively affecting the wheat performance. Adjuvant type and concentration caused no significant variation in grain Zn concentration. CONCLUSION: Overall, without foliar burn, wheat treated with 10 g kg-1 ZnEDTA foliar spray had the best performance with regard to grain Zn concentration and grain yield, which could have considerable implications for Zn biofortification of wheat grain. © 2021 Society of Chemical Industry.

Diet quality trajectories and cardiovascular phenotypes/metabolic syndrome risk by 11-12 years.

OBJECTIVE: To investigate associations between early-life diet trajectories and preclinical cardiovascular phenotypes and metabolic risk by age 12 years. METHODS: Participants were 1861 children (51% male) from the Longitudinal Study of Australian Children. At five biennial waves from 2-3 to 10-11 years: Every 2 years from 2006 to 2014, diet quality scores were collected from brief 24-h parent/self-reported dietary recalls and then classified using group-based trajectory modeling as 'never healthy' (7%), 'becoming less healthy' (17%), 'moderately healthy' (21%), and 'always healthy' (56%). At 11-12 years: During children's physical health Child Health CheckPoint (2015-2016), we measured cardiovascular functional (resting heart rate, blood pressure, pulse wave velocity, carotid elasticity/distensibility) and structural (carotid intima-media thickness, retinal microvasculature) phenotypes, and metabolic risk score (composite of body mass index z-score, systolic blood pressure, high-density lipoproteins cholesterol, triglycerides, and glucose). Associations were estimated using linear regression models (n = 1100-1800) adjusted for age, sex, and socioeconomic position. RESULTS: Compared to 'always healthy', the 'never healthy' trajectory had higher resting heart rate (2.6 bpm, 95% CI 0.4, 4.7) and metabolic risk score (0.23, 95% CI 0.01, 0.45), and lower arterial elasticity (-0.3% per 10 mmHg, 95% CI -0.6, -0.1) and distensibility (-1.2%, 95% CI -1.9, -0.5) (all effect sizes 0.3-0.4). Heart rate, distensibility, and diastolic blood pressure were progressively poorer for less healthy diet trajectories (linear trends p ≤ 0.02). Effects for systolic blood pressure, pulse wave velocity, and structural phenotypes were less evident. CONCLUSIONS: Children following the least healthy diet trajectory had poorer functional cardiovascular phenotypes and metabolic syndrome risk, including higher resting heart rate, one of the strongest precursors of all-cause mortality. Structural phenotypes were not associated with diet trajectories, suggesting the window to prevent permanent changes remains open to at least late childhood.

Poorly crystalline Fe(â ¡) mineral phases induced by nano zero-valent iron are responsible for Cd stabilization with different soil moisture conditions and soil types.

Nano zero-valent iron (nZVI) is a promising remediation material for Cd-contaminated soil, but questions remain regarding the effects of nZVI-induced Fe oxides on Cd availability with different soil types and moisture conditions. To identify the changes in Cd availability and Fe mineral phases resulting from the application of nZVI, three types of Cd-spiked soils with 0.1% nZVI amendment were incubated under different moisture conditions with water-holding capacities (WHCs) of 30%, 60%, and 180%. The availability of Cd was significantly decreased in yellow and black soils amended with nZVI, with fewer changes being observed in cinnamon soil. The limited effect of nZVI on Cd stabilization was due to the extremely low content of poorly crystalline Fe phases in cinnamon soil. The Cd stabilization efficiency of nZVI was higher in the flooding soils (180% WHC) than in the non-flooding yellow and black soils (30% and 60% WHC, respectively). Moreover, the addition of nZVI promoted the formation of less-available forms of Cd (Fe-oxide-bound Cd in yellow soil and Fe-oxide-bound and organic-material-bound Cd in black soil) under the flooding condition. The decrease in extractable Cd was strongly related to the increase in poorly crystalline Fe(Ⅱ) mineral phases among the three soils and various soil moisture contents. Although 0.1% nZVI amendment induced the dissolution of Mn oxides, it did not hinder the Cd stabilization in the three soils. Overall, this study indicates that increased amounts of poorly crystalline Fe(Ⅱ) compounds due to nZVI amendment play a critical role in the stabilization of Cd in soils.

Associations of retinal microvascular caliber with large arterial function and structure: A population-based study of 11 to 12 year-olds and midlife adults.

OBJECTIVE: We examined associations between retinal microvascular and large arterial phenotypes to explore relationships between the micro- and macro-vasculature in childhood and midlife. METHODS: Participants were 1288 children (11-12 years, 50.9% female) and 1264 adults (mean age 44 years, 87.6% female) in a cross-sectional population-based study. Exposures were retinal arteriolar and venular caliber quantified from retinal images. Outcomes included arterial function (pulse wave velocity; carotid arterial elasticity) and structure (carotid intima-media thickness). Multivariable regression models were performed adjusting for age, sex, and family socioeconomic position. RESULTS: In children, one standard deviation wider arteriolar caliber was associated with slower pulse wave velocity (-0.15 SD, 95% CI -0.21, -0.09) and higher elasticity (0.13 SD, 95% CI 0.06, 0.20); per SD wider venular caliber was associated with faster pulse wave velocity (0.09 SD, 95% CI 0.03, 0.15) and lower elasticity (-0.07 SD, 95% CI -0.13, -0.01). The size of adult associations was approximately double. Wider arteriolar caliber was associated with smaller carotid intima-media thickness (-0.09 SD, 95% CI -0.16, -0.03) in adults but not children. Venular caliber and carotid intima-media thickness showed little evidence of association. CONCLUSIONS: Narrower retinal arterioles and wider venules are associated with large arterial function as early as mid-childhood. Associations strengthen by midlife and also extend to arterial structure, although effect sizes remain small.

Do body mass index and waist-to-height ratio over the preceding decade predict retinal microvasculature in 11-12 year olds and midlife adults?

BACKGROUND/OBJECTIVES: Microvascular changes may contribute to obesity-associated cardiovascular disease. We examined whether body mass index (BMI) and waist-to-height ratio (WHtR) (1) at multiple earlier time points and (2) decade-long trajectories predicted retinal microvascular parameters in mid-childhood/adulthood. METHODS: Participants/design: 1288 11-12 year olds (51% girls) and 1264 parents (87% mothers) in the population-based Child Health CheckPoint (CheckPoint) module within the Longitudinal Study of Australian Children (LSAC). LSAC exposure measures: biennial BMI z-score and WHtR for children at five time points from age 2-3 to 10-11 years and self-reported parent BMI at six time points from child age 0-1 years to 10-11 years. CheckPoint outcome measures: retinal arteriolar and venular caliber. ANALYSES: BMI/WHtR trajectories were identified by group-based trajectory modeling; linear regression models estimated associations between BMI/WHtR at each time point/trajectories and later retinal vascular caliber, adjusted for age, sex, and family socioeconomic status. RESULTS: In time point analyses, higher child BMI/WHtR from age 4 to 5 years was associated with narrower arteriolar caliber at the age of 11-12 years, but not venular caliber. For example, each standard deviation higher in BMI z-score at 4-5 years was associated with narrower arteriolar caliber at 11-12 years (standardized mean difference (SMD): -0.05, 95% confidence interval (CI): -0.10 to 0.01); by 10-11 years, associations had doubled to -0.10 (95% CI: -0.16 to -0.05). In adults, these finding were similar, except the magnitude of BMI and arteriolar associations were similar across all time points (SMD: -0.11 to -0.13). In child and adult BMI trajectory analyses, less favorable trajectories predicted narrower arteriolar (p-trend < 0.05), but not venular (p-trend > 0.1), caliber. Compared with those in the average BMI trajectory, SMDs in arterial caliber for children and adults in the highest trajectory were -0.25 (95% CI: -0.44 to -0.07) and -0.42 (95% CI: -0.73 to -0.10), respectively. Venular caliber showed late associations with child WHtR, but not with BMI in children or adults. CONCLUSIONS: Associations of decade-long high BMI trajectories with narrowed retinal arteriolar caliber emerge in children, and are clearly evident by midlife. Adiposity appears to exert its early adverse life course impacts on the microcirculation more via arteriolar than venular mechanisms.

Cardiovascular health and retinal microvascular geometry in Australian 11-12 year-olds.

Traditional retinal microvascular parameters (smaller arteriolar and greater venular caliber) are associated with cardiovascular risk factors, pre-clinical vascular phenotypes and clinical cardiovascular events in adults. Although novel retinal microvascular geometric parameters showed analogous associations in adults, less is known whether these parameters are associated with cardiovascular health from childhood. In a population-based cross-sectional study in children (n = 1126, mean age 11.4 years, 50.3% girls), we examined associations of cardiovascular risk factors and pre-clinical arterial phenotypes with retinal geometric parameters. Cardiovascular parameters included body mass index (BMI), an inflammatory marker (GlycA), low-density lipoprotein and high-density lipoprotein (HDL) cholesterol, systolic (SBP) and diastolic blood pressure, large artery functional (pulse wave velocity, PWV and carotid arterial elasticity) and structural (carotid intima-media thickness) phenotypes. Retinal geometric parameters (fractal dimension (Df) and tortuosity) were quantified from retinal images. Multivariable regression models were performed and adjusted for potential confounders. Higher values for BMI, SBP and PWV showed weak associations with lower (i.e. worse) arteriolar but not venular Df (standardized mean difference (SMD) ranging from -0.07 to -0.09, 95% CIs -0.15 to -0.01). Higher HDL was associated with greater arteriolar Df (SMD 0.07, 95% CI 0.01 to 0.13). Only higher SBP was associated with higher (i.e. worse) arteriolar but not venular tortuosity (SMD 0.09, 95% CI 0.02 to 0.16). In generally healthy children, some risk factors and pre-clinical arterial phenotypes show small associations with retinal geometric parameters. In childhood, emerging relationships between microvascular parameters and cardiometabolic risk may be better described by retinal vascular caliber than by geometric parameters.

Drug Loading in Poly(butyl cyanoacrylate)-Based Polymeric Microbubbles.

Microbubbles (MB) are routinely used ultrasound (US) contrast agents that have recently attracted increasing attention as stimuli-responsive drug delivery systems. To better understand MB-based drug delivery, we studied the role of drug hydrophobicity and molecular weight on MB loading, shelf-life stability, US properties, and drug release. Eight model drugs, varying in hydrophobicity and molecular weight, were loaded into the shell of poly(butyl cyanoacrylate) (PBCA) MB. In the case of drugs with progesterone as a common structural backbone (i.e., for corticosteroids), loading capacity and drug release correlated well with hydrophobicity and molecular weight. Conversely, when employing drugs with no structural similarity (i.e., four different fluorescent dyes), loading capacity and release did not correlate with hydrophobicity and molecular weight. All model drug-loaded MB formulations could be equally efficiently destroyed upon exposure to US. Together, these findings provide valuable insights on how the physicochemical properties of (model) drug molecules affect their loading and retention in and US-induced release from polymeric MB, thereby facilitating the development of drug-loaded MB formulations for US-triggered drug delivery.

Bi3+-Doped BaYF5:Yb,Er Upconversion Nanoparticles with Enhanced Luminescence and Application Case for X-ray Computed Tomography Imaging.

In this work, BaYF5:20%Yb3+/2%Er3+/x%Bi3+ (abbreviated as BaYF5:Yb,Er,Bix, where x = 0-3.0) upconversion nanoparticles (UCNPs) with various doping concentrations of Bi3+ were synthesized through a simple hydrothermal method. The influence of the doping amount of Bi3+ on the microstructures and upconversion luminescence (UCL) properties of the BaYF5:Yb,Er,Bix UCNPs was studied in detail. The doping concentration of Bi3+ has little influence on the microstructures of the UCNPs but significantly impacts their UCL intensities. Under excitation of a 980 nm near-IR laser, the observed UCL intensities for the BaYF5:Yb,Er,Bix UCNPs display first an increasing trend and then a decreasing trend with an increase in the ratio x, giving a maximum at x = 2.5. A possible energy-transfer process and simplified energy levels of the BaYF5:Yb,Er,Bix UCNPs were proposed. The potential of the BaYF5:Yb,Er,Bix UCNPs as contrast agents for computerized tomography (CT) imaging was successfully demonstrated. An obvious accumulation of BaYF5:Yb,Er,Bix in tumor sites was achieved because of high passive targeting by the enhanced permeability and retention effect and relatively low uptake by a reticuloendothelial system such as liver and spleen. This work paves a new route for the design of luminescence-enhanced UNCPs as promising bioimaging agents for cancer theranostics.

2,3,5,4'-Tetrahydroxy-stilbene-2-O-beta-d-glucoside induces autophagy-mediated apoptosis in hepatocytes by upregulating miR-122 and inhibiting the PI3K/Akt/mTOR pathway: implications for its hepatotoxicity.

CONTEXT: The potential hepatotoxicity of Polygoni Multiflori Radix (PMR) has attracted much attention, but the specific mechanism of inducing hepatotoxicity is still unclear due to the complexity of its components. OBJECTIVE: This study investigated the specific mechanism by which 2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-d-glucoside (TSG) regulates hepatotoxicity. MATERIALS AND METHODS: The toxic effects of TSG (10, 100, 1000 µg/mL) on WRL-68 cells were examined using MTT, flow cytometry, and LDH assay after 24 h of incubation. Untreated cells served as the control. Gene and protein expression levels were determined by quantitative real-time PCR and Western blot, respectively. Immunofluorescence analysis was conducted to investigate the expression of light chain 3 (LC3). Luciferase activity assay was used to assess the targeted regulation of RUNX1 by miR-122. RESULTS: The half maximal inhibitory concentration (IC50) of TSG in WRL-68 cells was calculated as 1198.62 µg/mL. TSG (1000 µg/mL) inhibited cell viability and LDH activity and promoted WRL-68 cell apoptosis by inducing autophagy. Subsequent findings showed that TSG induced autophagy and promoted apoptosis in WRL-68 cells by downregulating the levels of p-PI3K, p-Akt, and p-mTOR proteins, while RUNX1 overexpression rescued this inhibition. Additionally, the effect of TSG on hepatocyte apoptosis was reversed by miR-122 knockdown. Furthermore, bioinformatics and dual luciferase reporter assay results indicated that miR-122 targeted RUNX1. DISCUSSION AND CONCLUSIONS: Our data demonstrate for the first time that TSG regulates hepatotoxicity, possibly by upregulating miR-122 and inhibiting the RUNX1-mediated PI3K/Akt/mTOR pathway to promote autophagy and induce hepatocyte apoptosis. Further in vivo research is necessary to verify our conclusion.