Intercritically Annealed Medium-Manganese Steel: Insights into Microstructural and Microtextural Evolution, Strain Distribution, and Grain Boundary Characteristics.

Aluminum-incorporated medium-manganese steel (MMnS) has potential for lightweight transport applications owing to its impressive mechanical properties. Increasing the austenite volume fraction and making microstructural changes are key to manufacturing MMnS. However, the grain boundary character and strain distribution of intercritically annealed low-density MMnS have not been extensively scrutinized, and the effects of crystallographic texture orientation on tensile properties remain ambiguous. Therefore, in this study, the microstructure, microtexture, strain distribution, and grain boundary characteristics of a hot-rolled medium-Mn steel (Fe-0.2 C-4.3 Al-9.4 Mn (wt%)) were investigated after intercritical annealing (IA) at 750, 800, or 850 °C for 1 h. The results show that the 800 °C annealed sample exhibited the highest austenite volume fraction among the specimens (60%). The duplex microstructure comprised lath-type γ-austenite, fine α-ferrite, and coarse δ-ferrite. As the IA temperature increased, the body-centered cubic phase orientation shifted from <001> to <111>. At higher temperatures, the face-centered cubic phase was oriented in directions ranging from <101> to <111>, and the sums of the fractions of high-angle grain boundaries and coincidence-site-lattice special boundaries were significantly increased. The 800 °C annealed sample with a high austenite content and strong γ-fiber {111}//RD orientation demonstrated a noteworthy tensile strength (1095 MPa) and tensile elongation (30%).

Effectiveness of breath acetone monitoring in reducing body fat and improving body composition: a randomized controlled study.

When attempts to lose body fat mass frequently fail, breath acetone (BA) monitoring may assist fat mass loss during a low-carbohydrate diet as it can provide real-time body fat oxidation levels. This randomized controlled study aimed to evaluate the effectiveness of monitoring BA levels and providing feedback on fat oxidation during a three-week low-carbohydrate diet intervention. Forty-seven participants (mean age = 27.8 ± 4.4 years, 53.3% females, body mass index = 24.1 ± 3.4 kg m-2) were randomly assigned to three groups (1:1:1 ratio): daily BA assessment with a low-carbohydrate diet, body weight assessment (body scale (BS)) with a low-carbohydrate diet, and low-carbohydrate diet only. Primary outcome was the change in fat mass and secondary outcomes were the changes in body weight and body composition. Forty-five participants completed the study (compliance rate: 95.7%). Fat mass was significantly reduced in all three groups (allP< 0.05); however, the greatest reduction in fat mass was observed in the BA group compared to the BS (differences in changes in fat mass, -1.1 kg; 95% confidence interval: -2.3, -0.2;P= 0.040) and control (differences in changes in fat mass, -1.3 kg; 95% confidence interval: -2.1, -0.4;P= 0.013) groups. The BA group showed significantly greater reductions in body weight and visceral fat mass than the BS and control groups (allP< 0.05). In addition, the percent body fat and skeletal muscle mass were significantly reduced in both BA and BS groups (allP< 0.05). However, no significant differences were found in changes in body fat percentage and skeletal muscle mass between the study groups. Monitoring BA levels, which could have motivated participants to adhere more closely to the low-carbohydrate diet, to assess body fat oxidation rates may be an effective intervention for reducing body fat mass (compared to body weight assessment or control conditions). This approach could be beneficial for individuals seeking to manage body fat and prevent obesity.

Intelligent Estimation of Exercise Induced Energy Expenditure Including Excess Post-Exercise Oxygen Consumption (EPOC) with Different Exercise Intensity.

The limited availability of calorimetry systems for estimating human energy expenditure (EE) while conducting exercise has prompted the development of wearable sensors utilizing readily accessible methods. We designed an energy expenditure estimation method which considers the energy consumed during the exercise, as well as the excess post-exercise oxygen consumption (EPOC) using machine learning algorithms. Thirty-two healthy adults (mean age = 28.2 years; 11 females) participated in 20 min of aerobic exercise sessions (low intensity = 40% of maximal oxygen uptake [VO2 max], high intensity = 70% of VO2 max). The physical characteristics, exercise intensity, and the heart rate data monitored from the beginning of the exercise sessions to where the participants' metabolic rate returned to an idle state were used in the EE estimation models. Our proposed estimation shows up to 0.976 correlation between estimated energy expenditure and ground truth (root mean square error: 0.624 kcal/min). In conclusion, our study introduces a highly accurate method for estimating human energy expenditure during exercise using wearable sensors and machine learning. The achieved correlation up to 0.976 with ground truth values underscores its potential for widespread use in fitness, healthcare, and sports performance monitoring.

Effects of the Mg Content on Microstructural and Corrosion Characteristics of Hot-Dip Al-Si-Mg Alloy-Coated Steel Sheets.

Hot-dip Al-Si alloy coatings with excellent resistance to corrosion and high-temperature oxidation have emerged as promising lightweight substitutes for conventional corrosion-resistant coatings. The introduction of Mg can be an effective strategy for enhancing the sacrificial protection capability of Al-Si coatings. In this study, the effects of Mg addition on the morphology, electrochemical behavior, and mechanical properties of Al-Si coatings were investigated, along with the Mg-content optimization of the coating layer. Adding Mg promoted the formation of finely distributed eutectic intermetallic phases, such as Al/Mg2Si and the primary Mg2Si phase. Notably, the Mg2Si phase coarsened significantly when ≥15 wt.% of Mg was added. In addition, an Al3Mg2 intermetallic compound was observed in coating layers containing >20 wt.% of Mg, reducing the adhesion of the coating layers. Samples containing 5-10 wt.% of Mg exhibited excellent corrosion resistance (owing to a uniform distribution of the fine eutectic Al/Mg2Si phase and the formation of stable corrosion products), whereas those containing 20 wt.% of Mg exhibited unremarkable corrosion resistance (owing to the formation of an Al3Mg2 phase that is susceptible to intergranular corrosion).

Comparisons of the prediction models for undiagnosed diabetes between machine learning versus traditional statistical methods.

We compared the prediction performance of machine learning-based undiagnosed diabetes prediction models with that of traditional statistics-based prediction models. We used the 2014-2020 Korean National Health and Nutrition Examination Survey (KNHANES) (N = 32,827). The KNHANES 2014-2018 data were used as training and internal validation sets and the 2019-2020 data as external validation sets. The receiver operating characteristic curve area under the curve (AUC) was used to compare the prediction performance of the machine learning-based and the traditional statistics-based prediction models. Using sex, age, resting heart rate, and waist circumference as features, the machine learning-based model showed a higher AUC (0.788 vs. 0.740) than that of the traditional statistical-based prediction model. Using sex, age, waist circumference, family history of diabetes, hypertension, alcohol consumption, and smoking status as features, the machine learning-based prediction model showed a higher AUC (0.802 vs. 0.759) than the traditional statistical-based prediction model. The machine learning-based prediction model using features for maximum prediction performance showed a higher AUC (0.819 vs. 0.765) than the traditional statistical-based prediction model. Machine learning-based prediction models using anthropometric and lifestyle measurements may outperform the traditional statistics-based prediction models in predicting undiagnosed diabetes.

Revisiting the phylogeny of the family Miridae (Heteroptera: Cimicomorpha), with updated insights into its origin and life history evolution.

Heteroptera is one of the most successfully adapted groups on Earth and can be observed in almost every environment. Within the evolution of heteropteran insects, Miridae show remarkable diversity (>11,700 spp.), accounting for a quarter of all Heteroptera. However, their phylogeny is still unclear, and no plausible theory for the driving force of their diversification has been established. In this work, we provide new suggestions for the phylogeny of Miridae using a larger dataset than previous studies. In addition, we suggest an alternative evolutionary history based on newly calibrated divergence dates for Miridae and its subordinate groups, and present probable factors of the family's success in terms of species diversity. The entire dataset comprises 16 outgroups and 188 ingroup taxa including all seven known subfamilies and 37 out of 45 known tribes. Each species is aligned as 3,577 bp with six molecular loci (COI, 16S rRNA, 18S rRNA, 28S rRNA D3 region, H2A, and H3A). Among the molecular markers, we are the first to test histone genes (H2A, H3A) in Miridae. Our results raise the following points about phylogenetic relationships: i) The earliest group to diverge from Miridae was Monaloniini (Bryocorinae). ii) Bryocorinae and Cylapinae are polyphyletic, Deraeocorinae and Orthotylinae also rendered as non-monophyletic group. iii) Termatophylini and Coridromiini separated from Deraeocorinae and Orthotylinae respectively. iv) Four large tribes, Orthotylini, Phylini, Deraeocorini and Mirini are non-monophyletic. The results from our ancestral state reconstruction and divergence date estimation suggest the following: i) Miridae first diverged during the Late Jurassic (approx. 163.4 Mya), and the divergence dates of most subfamilies and tribes overlap with angiosperm radiation, which perhaps synergized their diversification. ii) Ancestral reconstruction results for Miridae reveal it to be predominantly phytophagous and diverge to oligophagy mainly in plant-tissue habitats, which could have allowed the mirids to select optimal tactics as plant-dwellers. iii) The common ancestor of Miridae originated among plant-dwellers mainly on Eudicots, and that tendency was largely maintained, but sporadic host shifts also occurred.

Long-term association of pericardial adipose tissue with incident diabetes and prediabetes: the Coronary Artery Risk Development in Young Adults Study.

OBJECTIVES: We examined whether pericardial adipose tissue (PAT) is predictive of prediabetes and type 2 diabetes over time. METHODS: In total, 2,570 adults without prediabetes/diabetes from the Coronary Artery Risk Development in Young Adults Study were followed up over 15 years. PAT volume was measured by computed tomography scans, and the new onset of prediabetes/diabetes was examined 5 years, 10 years, and 15 years after the PAT measurements. Multivariable Cox regression models were used to examine the association between the tertile of PAT and incident prediabetes/diabetes up to 15 years later. The predictive ability of PAT (vs. waist circumference [WC], body mass index [BMI], waist-to-height ratio [WHtR]) for prediabetes/diabetes was examined by comparing the area under the receiver operating characteristic curve (AUC). RESULTS: The highest tertile of PAT was associated with a 1.56 times (95% confidence interval [CI], 1.03 to 2.34) higher rate of diabetes than the lowest tertile; however, no association was found between the highest tertile of PAT and prediabetes in the fully adjusted models, including additional adjustment for BMI or WC. In the fully adjusted models, the AUCs of WC, BMI, WHtR, and PAT for predicting diabetes were not significantly different, whereas the AUC of WC for predicting prediabetes was higher than that of PAT. CONCLUSIONS: PAT may be a significant predictor of hyperglycemia, but this association might depend on the effect of BMI or WC. Additional work is warranted to examine whether novel adiposity indicators can suggest advanced and optimal information to supplement the established diagnosis for prediabetes/diabetes.

Joint Association of Diabetes and Physical Activity With Falls Among Midlife and Older Adults: 2018 Behavioral Risk Factor Surveillance System.

PURPOSE: We examined joint associations of diabetes and physical activity (PA) with falls. DESIGN: Complex survey (cross-sectional) design using the 2018 Behavioral Risk Factor Surveillance System (Response rate was 53% (landline phones) and 46% (cellular phones)). SETTING: National survey in the U.S. SUBJECTS: Adults ≥45 years who self-reported diabetes status, PA, and falls (n = 295,282; 98.5% of eligible samples; N = 130,103,093) were classified into 4 groups: no diabetes-PA, no diabetes-no PA, diabetes-PA, diabetes-no PA. MEASURES: Self-reported PA, diabetes, falls, and major health characteristics. ANALYSIS: Poisson regression models were used to estimate the association of groups with any (≥1 fall) falls. RESULTS: Compared to no diabetes-active groups, no diabetes-inactive (Relative Risk (RR) = 1.22; 95% CI: 1.18, 1.26), diabetes-active (RR = 1.25; 95% CI: 1.20, 1.30), and diabetes-inactive (RR = 1.46; 95% CI: 1.41, 1.51) groups were more likely to report falls, independent of tested covariates. CONCLUSIONS: Leisure-time PA may mitigate the likelihood of falls in adults with and without diabetes. Our findings could be useful for healthcare providers or clinicians to promote the importance of PA in midlife and older adults who are at risk of falls and/or diabetes. More detailed longitudinal information on objectively-estimated PA and a more frequent fall calendar are warranted to prevent recall bias and temporal ambiguity (causality between PA and falls).

Association of Absolute and Relative Handgrip Strength with Prevalent Metabolic Syndrome in Adults: Korea National Health and Nutrition Examination Survey 2014-2018.

Maintaining or improving muscular strength may be a key preventive strategy for metabolic syndrome (MetS). However, whether the association of handgrip strength (HGS), as a well-established marker of whole-body muscular strength, with the prevalent metabolic syndrome (MetS) varies with age stratification remains unclear. Additionally, whether absolute of relative HGS is superior to another in predicting MetS is less clear. We examined the association of both relative and absolute HGS with the prevalence of MetS in different age groups. Korean adults aged ≥19 years (n = 28,146; 55.7% female) from the Korean National Health and Nutrition Examination Survey (2014-2018) were examined. HGS was categorized using tertile split (highest, intermediate, lowest) and participants were stratified into different age groups at 10-year intervals. Multivariable logistic regression models were used to examine the association between absolute/relative HGS tertiles and MetS with adjustment for covariates. Lower odds of MetS were observed across lower absolute HGS tertiles and the associations were significant in young participants (19-29 years) in both sexes (odds ratio (OR): 0.59 (95% CI: 0.38-0.92) for intermediate and OR: 0.55 (95% CI: 0.34-0.89) for lowest in males; OR: 0.36 (95% CI: 0.20-0.65) for intermediate and OR: 0.42 (95% CI: 0.24-0.74) for lowest in females; all p < 0.05). By contrast, higher odds of MetS were observed across lower relative HGS in all age groups in both sexes (in total participants, OR: 2.32 (95% CI: 2.06-2.62) for intermediate and OR: 3.69 (95% CI: 3.27-4.16) for lowest in males and OR: 2.04 (95% CI: 1.83-2.28) for intermediate and OR: 3.28 (95% CI: 2.94-3.65) for lowest in females all p < 0.05). The associations of both absolute and relative HGS with MetS attenuated with an increase in age. Our findings suggest that poor relative HGS, as a marker of muscular strength, and not absolute HGS, may be associated with a higher risk of MetS in adults. Our findings also suggest that relative HGS may overestimate MetS in young adults.

A review of the genus Orthotylus Fieber (Heteroptera: Miridae: Orthotylinae) in Korea, with a discussion on geographical variation and distributional records of O. salicis and O. riparius.

The plant but genus Orthotylus Fieber, 1858 in Korea is reviewed. One species, O. riparius Kulik is newly recorded from the Korean peninsula. Diagnostic characters of each species are discussed, with the images of adult specimen and genitalic structures. Additionally, a key to the Korean Orthotylus species is presented. Chinese record of O. riparius is excluded based on critical literature reviews. Observed variant of O. riparius Kulik and O. salicis Jakovlev are discussed.

Ten-Year Changes in Television Viewing and Physical Activity Are Associated With Concurrent 10-Year Change in Pericardial Adiposity: The Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: Longitudinal association of television (TV) viewing and moderate- to vigorous-intensity physical activity (MVPA) with pericardial adipose tissue (PAT) is unclear. METHODS: We studied Coronary Artery Risk Development in Young Adults Study participants transitioning from early to middle age at Coronary Artery Risk Development in Young Adults (CARDIA) exam years 15 (2000-2001; N = 1975, mean age = 40.4, 55.4% women, 45.3% Black) and 25 (2010-2011). TV viewing (in hours per day) and MVPA (in exercise units) were measured using a self-report questionnaire. PAT volume (in milliliters) was measured using computed tomography. Multivariable linear regression was used to examine the associations of tertiles of 10-year change (years 25-15) in TV viewing and MVPA with a concurrent change in PAT with adjustments for covariates. RESULTS: Participants in the highest tertile of 10-year increase in TV viewing had a greater increase in PAT (ß = 2.96 mL, P < .01). Participants in both middle (ß = -3.93 mL, P < .01) and highest (ß = -6.22 mL, P < .01) tertiles of 10-year changes in MVPA had smaller mean increases in PAT over 10 years when compared with the lowest tertile in fully adjusted models. CONCLUSIONS: Reducing or maintaining early-midlife levels of TV viewing and increasing MVPA may be associated with less PAT accumulation with age.

Quantifying physical activity across the midlife: Does consideration of perceived exertion matter?

Many questionnaires ascertain physical activity (PA) frequency, duration, and intensity to benchmark achievement of PA recommendations. However, most scoring algorithms utilize absolute intensity estimates when exertion may be influenced by age or health characteristics. This study quantified PA estimates with and without adjustments for perceived exertion and evaluated if differences were associated with individual-level characteristics. Women (n = 2,711) in the United States from the Study of Women's Health Across the Nation who completed ≥ 3 Kaiser Physical Activity Surveys (KPAS) across 8 biennial visits were included (baseline age: 46.4 ± 2.7 years). KPAS responses about activity mode and exertion were converted to metabolic equivalent of a task (METs) using the 2011 Compendium of Physical Activities to estimate absolute and perceived intensity-adjusted METs. Repeated measures (linear mixed effects) regression models were used to examine associations of sociodemographic and health-related characteristics with change in the difference between absolute MET estimates and perceived intensity-adjusted MET estimates. Older age (p < 0.001), Chinese (p < 0.001) and Japanese (p = 0.01) ethnicity, and current smoking (p = 0.001) were associated with positive differences between absolute and perceived intensity-adjusted MET estimates, which is suggestive of lower perceived-intensity physical activity. However, for most participants, absolute intensity-based estimates closely approximated perceived intensity-adjusted estimates over time. Traditional PA scoring techniques using absolute intensity estimates only may provide sufficient estimates of PA in longitudinal cohort studies of mid-life and older adult women.

Cross-Sectional and Longitudinal Associations of Lifestyle Behaviors with Pericardial Adipose Tissue: The MESA Study.

PURPOSE: We examined associations of sedentary behavior (SB), light-intensity physical activity (LPA), and moderate-to-vigorous intensity physical activity (MVPA) with pericardial adipose tissue (PAT). METHODS: Adults from the Multi-Ethnic Study of Atherosclerosis were included from exam years 1 (2000-2002; N = 6057; mean age, 62.2 yr; 52.9% female, 38.0% White; 12.8% Chinese American, 26.7% African American, 22.5% Hispanic American), 2 (2002-2004), and 3 (2004-2005). Weekly volume of SB, LPA, and MVPA (in MET-hours per week) was reported using a questionnaire. PAT volume (in cubic centimeters) was quantified using computed tomography, analysis of covariance, and repeated-measures linear mixed models with adjustment for covariates (sociodemographics, cardiovascular disease risk factors, inflammation, waist circumference) tested cross-sectional and longitudinal associations, respectively. RESULTS: In cross-sectional analysis, the highest tertile of SB (ß = 2.71; 95% confidence interval (CI), 0.69 to 4.73; P < 0.01) and the middle tertile of MVPA (ß = -1.97; 95% CI, -3.92 to -0.02; P < 0.05) were associated with PAT, whereas no association was observed for LPA in fully adjusted models. In longitudinal models, SB, LPA, and MVPA were not associated with PAT in the full study sample; however, LPA was inversely associated with PAT among Whites in stratified analysis (ß = -0.54; 95% CI, -0.95 to -0.13; P < 0.05). CONCLUSIONS: Lower SB and higher LPA (among Whites only) and MVPA may be associated with lower PAT, but additional longitudinal research is needed.

Cardiorespiratory Fitness in Adults Aged 18 to 34 Years and Long-Term Pericardial Adipose Tissue (from the Coronary Artery Risk Development in Young Adults Study).

Pericardial adipose tissue (PAT), an ectopic adipose depot surrounding the coronary arteries, is a pathogenic risk marker for cardiometabolic disease; however, the association between cardiorespiratory fitness (CRF) and PAT is unclear. Young adults (n = 2,614, mean age 25.1 years, 55.8% women, and 43.8% Black at baseline [1985 to 1986]) from the Coronary Artery Risk Development in Young Adults study were included. Maximal CRF was estimated at baseline, examination year 7 (1992 to 1993) and year 20 (2005 to 2006), using a symptom-limited maximal treadmill exercise test (duration in minutes) among those achieving ≥85% of age-predicted maximal heart rate. PAT volume (ml) was quantified at examination year 15 (2000 to 2001) and year 25 (2010 to 2011) using computed tomography. Multivariable linear and linear mixed regressions with covariates (sociodemographics, cardiovascular disease risk factors, inflammation, waist circumference) from baseline, year 7, and/or year 20 were used. Separate multivariable regression models revealed inverse associations of CRF at baseline, year 7, or year 20 with PAT at year 25 in fully adjusted models (all p <0.001). The linear mixed model showed that a 1-minute increase in treadmill exercise test duration over 20 years was associated with 1.49 ml lower subsequent PAT volume (p <0.001). In conclusion, findings suggest that higher CRF is inversely associated with subsequent PAT volume. Strategies to optimize CRF may be preventive against excessive PAT accumulation with age.

Enhanced Long-Term Reliability of Seal DeltaSpot Welded Dissimilar Joint between 6061 Aluminum Alloy and Galvannealed Steel via Excimer Laser Irradiation.

Structural-adhesive-assisted DeltaSpot welding was used to improve the weldability and mechanical properties of dissimilar joints between 6061 aluminum alloy and galvannealed HSLA steel. Evaluation of the spot-weld-bonded surfaces from lap shear tests after long-term exposure to chloride and a humid atmosphere (5% NaCl, 35 °C) indicated that the long-term mechanical reliability of the dissimilar weld in a corrosive environment depends strongly on the adhesive-Al6061 alloy bond strength. Corrosive electrolyte infiltrated the epoxy-based adhesive/Al alloy interface, disrupting the chemical interactions and decreasing the adhesion via anodic undercutting of the Al alloy. Due to localized electrochemical galvanic reactions, the surrounding nugget matrix suffered accelerated anodic dissolution, resulting in an Al6061-T6 alloy plate with degraded adhesive strength and mechanical properties. KrF excimer laser irradiation of the Al alloy before adhesive bonding removed the weakly bonded native oxidic overlayers and altered the substrate topography. This afforded a low electrolyte permeability and prevented adhesive delamination, thereby enhancing the long-term stability of the chemical interactions between the adhesive and Al alloy substrate. The results demonstrate the application of excimer laser irradiation as a simple and environmentally friendly processing technology for robust adhesion and reliable bonding between 6061 aluminum alloy and galvannealed steel.

Cardiopulmonary fitness but not muscular fitness associated with visceral adipose tissue mass.

PURPOSE: The purpose of this study is to identify the association between physical fitness (cardiopulmonary and musculoskeletal) and the distribution of abdominal fat in overweight and obese adults. METHODS: Of the total 102 overweight and obese participants, 99 participants completed all measurements. Cardiopulmonary fitness was assessed by maximal oxygen consumption test and muscular fitness was assessed using 10 repetition max. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were assessed by computed tomography (CT) at the level of lumbar spine 4-5. RESULTS: Cardiopulmonary fitness was inversely associated with both VAT and SAT, while muscular fitness only inversely associated with SAT. Multiple linear regression analyses indicated that gender, age, and cardiopulmonary fitness, but not muscular fitness, were associated with VAT, and age, cardiopulmonary fitness, and muscular fitness were significantly associated with SAT. CONCLUSIONS: Cardiopulmonary fitness is more closely related to both VAT and SAT while muscular fitness is related with SAT.

Moderate-to-vigorous intensity physical activity trajectories during adolescence and young adulthood predict adiposity in young adulthood: The Iowa Bone Development Study.

This study examined the associations of moderate-to-vigorous intensity physical activity (MVPA) trajectories in adolescence through young adulthood with adiposity in young adults. Participants from The Iowa Bone Development Study cohort were longitudinally assessed (N = 297; 57% female). Accelerometry-measured MVPA (min/day) at ages 15 through 23 years, and fat mass and visceral adipose tissue mass indices (kg/m2, g/m2) derived from dual-energy X-ray absorptiometry scans at age 23 years were analyzed. Latent trajectory analyses classified MVPA into two patterns. Multivariable linear regression analyses showed that being in the high MVPA trajectory group was associated with lower fat mass index z-scores. Individuals who were consistently active with high MVPA (vs. moderately active with decreasing MVPA) during adolescence up until early young adulthood had less accumulation of total body adiposity in young adulthood. This study suggests that adopting a consistently active lifestyle throughout adolescence can result in healthier body composition in young adulthood.

Multiplex quantitative analysis of stroma-mediated cancer cell invasion, matrix remodeling, and drug response in a 3D co-culture model of pancreatic tumor spheroids and stellate cells.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a stroma-rich carcinoma, and pancreatic stellate cells (PSCs) are a major component of this dense stroma. PSCs play significant roles in metastatic progression and chemoresistance through cross-talk with cancer cells. Preclinical in vitro tumor model of invasive phenotype should incorporate three-dimensional (3D) culture of cancer cells and PSCs in extracellular matrix (ECM) for clinical relevance and predictability. METHODS: PANC-1 cells were cultured as tumor spheroids (TSs) using our previously developed minipillar chips, and co-cultured with PSCs, both embedded in collagen gels. Effects of PSC co-culture on ECM fiber network, invasive migration of cancer cells, and expression of epithelial-mesenchymal transition (EMT)-related proteins were examined. Conditioned media was also analyzed for secreted factors involved in cancer cell-PSC interactions. Inhibitory effect on cancer cell invasion was compared between gemcitabine and paclitaxel at an equitoxic concentration in PANC-1 TSs co-cultured with PSCs. RESULTS: Co-culture condition was optimized for the growth of TSs, activation of PSCs, and their interaction. Increase in cancer cell invasion via ECM remodeling, invadopodia formation and EMT, as well as drug resistance was recapitulated in the TS-PSC co-culture, and appeared to be mediated by cancer cell-PSC interaction via multiple secreted factors, including IL-6, IL-8, IGF-1, EGF, TIMP-1, uPA, PAI-1, and TSP-1. Compared to gemcitabine, paclitaxel showed a greater anti-invasive activity, which was attributed to suppresion of invadopodia formation in cancer cells as well as to PSC-specific cytotoxicity abrogating its paracrine signaling. CONCLUSIONS: Here, we established 3D co-culture of TSs of PANC-1 cells and PSCs using minipillar histochips as a novel tumoroid model of PDAC. Our results indicate usefulness of the present co-culture model and multiplex quantitative analysis method not only in studying the role of PSCs and their interactions with tumor cell towards metastatic progression, but also in the drug evaluation of stroma-targeting drugs.

Effects of alternate day fasting and exercise on cholesterol metabolism in overweight or obese adults: A pilot randomized controlled trial.

BACKGROUND AND PURPOSE: The objective of this pilot randomized controlled trial was to investigate the effect of alternate day fasting (ADF) and exercise on serum sterol signatures, which are surrogate markers of cholesterol absorption and biosynthesis. METHODS: We randomly assigned 112 overweight or obese participants to four groups: 1) ADF and exercise (E-ADF); 2) ADF; 3) exercise; and 4) control. We studied 31 completers in this exploratory analysis and measured their serum sterol signatures using gas chromatography-mass spectrometry. RESULTS: After intervention, most serum sterol signatures that correspond to cholesterol metabolism were significantly different between groups (p < 0.05 by analysis of covariance [ANCOVA]). We found no differences in plant sterols, which are markers of cholesterol absorption. In the exercise group, desmosterol, cholesteryl esters, and oxysterols decreased significantly. Furthermore, only changes in physical activity levels negatively correlated with changes in the metabolic ratios of desmosterol and 7-dehydrocholesterol to cholesterol, which reflect cholesterol biosynthesis (r = -0.411; p = 0.030, and r = -0.540; p = 0.003, respectively). CONCLUSION: These findings suggest that exercise with or without ADF improves cholesterol metabolism as measured by serum sterol signatures, and increased physical activity has a greater effect on cholesterol biosynthesis than weight reduction or calorie restriction.

Effects of alternate day calorie restriction and exercise on cardio-metabolic risk factors in overweight and obese adults: an exploratory randomized controlled study.

BACKGROUND: It has been recognized that alternate day calorie restriction (ADCR) or exercise has positive effects on cardio-metabolic risk factors. It is unclear whether the combined effect of ADCR and exercise (aerobic + resistance training) influences risk. We investigated effects of an 8-week ADCR and exercise program (aerobic + resistance training) on cardio-metabolic risk factors in overweight and obese adults. METHODS: This study randomized 45 overweight or obese but healthy adults (F = 26, M = 19; aged about 32 to 40 years) into 4 groups: ADCR (n = 13), exercise (n = 10), exercise plus ADCR (n = 12), and control (n = 10) for 8 weeks. Body composition, blood lipids profile, and insulin resistance were measured. The intention to treat (ITT) method was used to analyze all participants that were randomized. RESULTS: A total of 35 participants completed the trial (78%). Body weight, body mass index, waist circumference, fat mass and percent body fat were reduced in the exercise plus ADCR group (- 3.3 ± 2.4 kg, p < 0.01; - 1.3 ± 1.0 kg/m2, p < 0.01; - 4.1 ± 3.9 cm, p < 0.01; - 2.7 ± 2.0 kg, p < 0.01; - 2. 5 ± 2.2%, p < 0.01). Insulin, glucose, homeostasis model assessment insulin resistance and triglyceride (- 2.9 ± 4.1 µIU/ml, p < 0.05; - 10.9 ± 16.9 mg/dl, p < 0.05; - 0.9 ± 1.3, p < 0.05; - 43.8 ± 41.9 mg/dl, p < 0.01) decreased in the exercise plus ADCR group only. CONCLUSIONS: ADCR and exercise both proved to be beneficial, but the combined intervention was most effective at inducing beneficial changes in body weight, body composition, glucose, insulin, insulin resistance and triglyceride in overweight and obese adults. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03652532 , Registered August 28, 2018, 'retrospectively registered'.