Long-Term Effect of PNPLA3 on the Aggravation of Nonalcoholic Fatty Liver Disease in a Biopsy-Proven Cohort.

The PNPLA3 rs738409 G allele increases the risk of not only nonalcoholic fatty liver disease (NAFLD) but also nonalcoholic steatohepatitis (NASH) or fibrosis.1 It also affects the prognosis of patients with NAFLD in specific conditions. After liver transplantation, patients with NAFLD carrying the rs738409 GG genotype have a higher risk of graft steatosis2 or development of hepatocellular carcinoma.3 In addition, rs738409 modifies the effects of medical intervention: patients with NAFLD carrying the GG genotype showed a lower effect of omega-3 polyunsaturated fatty acid treatment on the reduction of liver fat;4 in contrast, they were more sensitive to the beneficial effects of lifestyle modifications.5,6.

Extrinsic Calibration of Multiple 3D LiDAR Sensors by the Use of Planar Objects.

Three-dimensional light detection and ranging (LiDAR) sensors have received much attention in the field of autonomous navigation owing to their accurate, robust, and rich geometric information. Autonomous vehicles are typically equipped with multiple 3D LiDARs because there are many commercially available low-cost 3D LiDARs. Extrinsic calibration of multiple LiDAR sensors is essential in order to obtain consistent geometric information. This paper presents a systematic procedure for the extrinsic calibration of multiple 3D LiDAR sensors using plane objects. At least three independent planes are required within the common field of view of the LiDAR sensors. The planes satisfying the condition can easily be found on objects such as the ground, walls, or columns in indoor and outdoor environments. Therefore, the proposed method does not require environmental modifications such as using artificial calibration objects. Multiple LiDARs typically have different viewpoints to reduce blind spots. This situation increases the difficulty of the extrinsic calibration using conventional registration algorithms. We suggest a plane registration method for cases in which correspondences are not known. The entire calibration process can easily be automated using the proposed registration technique. The presented experimental results clearly show that the proposed method generates more accurate extrinsic parameters than conventional point cloud registration methods.

Changes of Apomorphine-Induced Vaginal Hemodynamics in an Ovariectomized Rat Model Using Near-Infrared Spectroscopic Probe.

INTRODUCTION: Female sexual arousal disorder (FSAD) can be caused by the change in vaginal structure due to the decline of estrogen and one of the main symptoms is vaginal dryness. FSAD is a prevalent problem afflicting women all over the world and thus the interest is growing on the matter, but related studies of monitoring FSAD using a non-invasive optical method barely have been carried out. AIM: This study aims to investigate the longitudinal changes in female sexual arousal response induced by apomorphine (APO) administration in the ovariectomized rat using near-infrared spectroscopy (NIRS) probe. METHODS: To elicit sexual arousal, APO was administered subcutaneously to animals (n = 6) before and after ovariectomy, and the changes in oxyhemoglobin (OHb), deoxyhemoglobin (RHb), total hemoglobin (THb) concentration, and temperature on the vaginal wall after APO administration were monitored bi-weekly for 8 weeks. Furthermore, estradiol hormone, vaginal secretion, and body weight have been measured for comparison with the results from vaginal hemodynamics. RESULTS: APO administration caused the increase of vaginal OHb and RHb concentration but a decrease in temperature. The amplitude of OHb, RHb, and THb increase induced by APO gradually decreased over 8 weeks after ovariectomy while the decrease in vaginal temperature became profound. The level of estradiol and vaginal secretions also decreased over 8 weeks after ovariectomy, but bodyweight showed an increasing trend. CONCLUSIONS: A comparison between the parameters measured from the NIRS probe and the others (estradiol level, amount of vaginal secretion, and body weight) proved that the NIRS has the potential as a monitoring tool to evaluate female sexual arousal response. Jeong H, Lee HS, Seong M, et al. Changes of Apomorphine-Induced Vaginal Hemodynamics in an Ovariectomized Rat Model Using Near-Infrared Spectroscopic Probe. J Sex Med 2021;18:1328-1336.

Co-culture of smooth muscle cells and endothelial cells on three-dimensional bioprinted polycaprolactone scaffolds for cavernosal tissue engineering.

PURPOSE: In vitro evaluation of polycaprolactone (PCL) scaffolds fabricated by a three-dimensional (3D) printing technique for tissue engineering applications in the corpus cavernosum. MATERIALS AND METHODS: PCL scaffolds were fabricated by use of a 3 D bioprinting system. The 3D-printed scaffolds had interconnected structures for cell ingrowth. Human aortic smooth muscle cells (haSMCs) were seeded on the scaffold and cultured for 5 days, and then human umbilical vein endothelial cells (HUVECs) were also added on the scaffolds and co-cultured with haSMCs for up to 7 days. The ability of these scaffolds to support the growth of HUVECs and haSMCs was investigated in vitro. 3 D strand-deposited scaffolds were characterized by scanning electron microscopy (SEM) images and porosity measurement. RESULTS: SEM images showed the surface of the PCL scaffolds to be well covered by HUVECs and haSMCs. Immunofluorescent staining of α-flk1 and α-smooth muscle actin on the HUVECs and haSMCs seeded scaffolds confirmed that the cells remained viable and proliferated throughout the time course of the culture. CONCLUSION: 3 D bioprinting of a PCL scaffold is feasible for co-culturing of HUVECs and haSMCs. This was a preliminary study to investigate the possibility of fabrication of tissue-engineered corpus cavernosum.

Design of an Optical Probe to Monitor Vaginal Hemodynamics during Sexual Arousal.

An optical probe was developed to measure the change of oxy-hemoglobin (OHb), deoxy- hemoglobin (RHb), and total hemoglobin (THb) along with temperature from the vaginal wall of female rats. Apomorphine (APO, 80 µg/kg) was administered to elicit sexual arousal in female Sprague Dawley rats (SD, 180-200 g). The behavior changes caused by APO administration were checked before monitoring vaginal responses. The changes of oxy-, deoxy-, and total hemoglobin concentration and the temperature from the vaginal wall were monitored before, during, and after APO administration. Animals were under anesthesia during the measurement. After APO administration, the concentration of OHb (55 ± 29 µM/DPF), RHb (33 ± 25 µM/DPF), and THb (83 ± 59 µM/DPF) in the vaginal wall increased in a few min, while saline administration did not cause any significant change. In case of the vaginal temperature change, APO decreased the temperature slightly in the vaginal wall while saline administration did not show any temperature change in the vaginal wall. As the outcomes demonstrated, the developed probe can detect hemodynamic and temperature variation in the vaginal wall. The hemodynamic information acquired by the probe can be utilized to establish an objective and accurate standard of female sexual disorders.

Validation of the MCNP6 code for SFR shielding design analysis.

In this paper, the uncertainty of the Monte Carlo code MCNP6 for the sodium-cooled fast reactor (SFR) shielding design is studied. Shielding analysis, which ensures the radiation safety of the core design, is challenging for the Monte Carlo modeling because it is associated with large uncertainties. In order to evaluate the performance of the MCNP6 relative to the shielding design of the SFR, four SFR shielding benchmarks from the Shielding Integral Benchmark Archive Database benchmark suite, i.e. JANUS Phase VIII, SDT12, EURAC_Na and HARMO_Na were selected and analysed. In this research, the weight window variance-reduction technique and the neutron data library ENDF/B-VII.1 were used in the modeling of the benchmark problems. The results and the validation of the MCNP6 models with the available measurement data are presented in this paper. These results contribute to the assessment of radiological protection and shielding design of the Korean Prototype Gen-IV Sodium-cooled Fast Reactor.

Effect of Substrate Roughness on Adhesion and Structural Properties of Ti-Ni Shape Memory Alloy Thin Film.

Ti-Ni shape memory alloy (SMA) thin films are very attractive material for industrial and medical applications such as micro-actuator, micro-sensors, and stents for blood vessels. An important property besides shape memory effect in the application of SMA thin films is the adhesion between the film and the substrate. When using thin films as micro-actuators or micro-sensors in MEMS, the film must be strongly adhered to the substrate. On the other hand, when using SMA thin films in medical devices such as stents, the deposited alloy thin film must be easily separable from the substrate for efficient processing. In this study, we investigated the effect of substrate roughness on the adhesion of Ti-Ni SMA thin films, as well as the structural properties and phase-transformation behavior of the fabricated films. Ti-Ni SMA thin films were deposited onto etched glass substrates with magnetron sputtering. Radio frequency plasma was used for etching the substrate. The adhesion properties were investigated through progressive scratch test. Structural properties of the films were determined via Feld emission scanning electron microscopy, X-ray diffraction measurements (XRD) and Energy-dispersive X-ray spectroscopy analysis. Phase transformation behaviors were observed with differential scanning calorimetry and low temperature-XRD. Ti-Ni SMA thin film deposited onto rough substrate provides higher adhesive strength than smooth substrate. However the roughness of the substrate has no influence on the growth and crystallization of the Ti-Ni SMA thin films.

Testosterone modulates endothelial progenitor cells in rat corpus cavernosum.

OBJECTIVE: To investigate the effects of testosterone on cavernosal endothelial progenitor cells (EPCs) in a castrated rat model. MATERIALS AND METHODS: In all, 45 male Sprague-Dawley rats (12-weeks old) were divided into control, surgical castration, and castration with testosterone replacement groups. The rats were castrated under ketamine anaesthesia, and testosterone was administered by daily subcutaneous injection of 3 mg/kg testosterone propionate. The corpus cavernosum was obtained after perfusion with 10 mL saline via the abdominal aorta 4 weeks later. The expression of EPC-specific markers [cluster of differentiation 34 (CD34), fetal liver kinase 1 (Flk1), and vascular endothelial (VE)-cadherin] was evaluated by flow cytometry analysis and immunofluorescence staining. RESULTS: CD34+/Flk1+ and CD34+/VE-cadherin+ cells were detected in the cavernosal sinusoidal endothelial space. Flow cytometry analysis showed that CD34 and Flk1 double positive cells (EPCs) comprised ≈3.79% of the corpus cavernosum in normal rats. The percentage of EPC marker-positive cells decreased significantly in the castration group (2.8%; P < 0.05) and was restored to 3.56% after testosterone supplementation. Confocal microscopy revealed that the numbers of CD34+/Flk1+ and CD34+/VE-cadherin+ cells decreased in castrated rats compared with controls, but were similar to control levels in rats receiving testosterone replacement. CONCLUSIONS: The EPC markers were expressed in the cavernosal sinusoidal endothelial space, and the numbers of resident EPCs were regulated by testosterone. These results suggest that testosterone replacement therapy may improve erectile function by modulating EPCs in patients with hypogonadism.

Ultralight, Robust, Thermal Insulating Silica Nanolace Aerogels Derived from Pickering Emulsion Templates.

Synthesis of silica aerogel insulators with ultralight weight and strong mechanical properties using a simplified technique remains challenging for functional soft materials. This study introduces a promising method for the fabrication of mechanically reinforced ultralight silica aerogels by employing attractive silica nanolace (ASNLs)-armored Pickering emulsion templates. For this, silica nanolaces (SiNLs) are fabricated by surrounding a cellulose nanofiber with necklace-shaped silica nanospheres. In order to achieve amphiphilicity, which is crucial for the stabilization of oil-in-water Pickering emulsions, hydrophobic alkyl chains and hydrophilic amine groups are grafted onto the surface of SiNLs by silica coupling reactions. Freeze-drying of ASNLs-armored Pickering emulsions has established a new type of aerogel system. The ASNLs-supported mesoporous aerogel shows 3-fold greater compressive strength, 4-fold reduced heat transfer, and a swift heat dissipation profile compared to that of the bare ASNL aerogel. Additionally, the ASNL aerogel achieves an ultralow density of 8 mg cm-3, attributed to the pore architecture generated from closely jammed emulsion drops. These results show the potential of the ASNL aerogel system, which is ultralight, mechanically stable, and thermally insulating and could be used in building services, energy-saving technologies, and the aerospace industry.

The clinical relevance of a polygenic risk score for type 2 diabetes mellitus in the Korean population.

The clinical utility of a type 2 diabetes mellitus (T2DM) polygenic risk score (PRS) in the East Asian population remains underexplored. We aimed to examine the potential prognostic value of a T2DM PRS and assess its viability as a clinical instrument. We first established a T2DM PRS for 5490 Korean individuals using East Asian Biobank data (269,487 samples). Subsequently, we assessed the predictive capability of this T2DM PRS in a prospective longitudinal study with baseline data and data from seven additional follow-ups. Our analysis showed that the T2DM PRS could predict the transition of glucose tolerance stages from normal glucose tolerance to prediabetes and from prediabetes to T2DM. Moreover, T2DM patients in the top-decile PRS group were more likely to be treated with insulin (hazard ratio = 1.69, p value = 2.31E-02) than were those in the remaining PRS groups. T2DM PRS values were significantly high in the severe diabetes subgroup, characterized by insulin resistance and ß -cell dysfunction (p value = 0.0012). The prediction models with the T2DM PRS had significantly greater Harrel's C-indices than did corresponding models without it. By utilizing prospective longitudinal study data and extensive clinical risk factor information, our analysis provides valuable insights into the multifaceted clinical utility of the T2DM PRS.

Effects of Home-Based Computerized Cognitive Training in Community-Dwelling Adults With Mild Cognitive Impairment.

OBJECTIVE: There is a growing importance for the home-based (HB) support services, and computerized cognitive training (CCT) has been reported as an effective intervention for cognitive impairment. However, there is still a need for further verification of the effect of HB-CCT. This study aimed to determine the effectiveness of HB-CCT on the cognitive function of community-dwelling adults with mild cognitive impairment (MCI) as well as safety in its use. METHODS: Fifty community-dwelling adults with MCI were included, of which 25 each were randomized to either HB-CCT or control groups. Evaluations of comprehensive cognition, memory, attention, language, executive function, and depression were performed before and after the intervention, including three times a week for eight weeks in the intervention group and eight weeks apart with no intervention in the control group. RESULTS: In baseline and post-evaluation comparisons, the HB-CCT group showed significant improvements, while the control group did not show significant changes. Statistically significant variations were noted between the HB-CCT and control groups in all post-intervention evaluations relative to baseline. Additionally, no side effects were observed. CONCLUSION: Beneficial effects on cognition and depression were noted in the intervention group compared with the control group, suggesting that HB-CCT may be a positive tool for cognitive improvement in adults with MCI.

Higher Genetic Risk for Type 2 Diabetes Is Associated With a Faster Decline of ß-Cell Function in an East Asian Population.

OBJECTIVE: While most genetic variants of type 2 diabetes (T2D) are suggested to be associated with ß-cell dysfunction cross sectionally, their association with the longitudinal change of ß-cell function remains largely unknown. RESEARCH DESIGN AND METHODS: We analyzed data from 6,311 participants without T2D at baseline (mean [SD] age 51.6 [8.7] years) from a community-based prospective cohort in Korea. Participants underwent biennial 2-h 75-g oral glucose tolerance tests (OGTTs) during 14 years of follow-up, and the OGTT-derived disposition index (DI) was used as a marker for ß-cell function. Genetic risk was quantified using the genome-wide polygenic risk score (PRS) and was stratified into low (1st quintile), intermediate (2nd-4th quintiles), and high (5th quintile) genetic risk. Lifestyle was assessed according to Life's Essential 8. RESULTS: During a mean follow-up of 10.9 years, 374 (29.6%), 851 (22.5%), and 188 (14.9%) participants developed T2D in the high, intermediate, and low genetic risk groups, respectively. Compared with the low genetic risk group, participants in the high genetic risk group had a 25% lower DI at baseline. Furthermore, in longitudinal analysis, we observed a 1.83-fold faster decline in log2-transformed DI per year (-0.034 vs. -0.019, P = 2.1 × 10-3; per 1-SD increase in T2D PRS, P = 1.2 × 10-4). Healthy lifestyle attenuated the rate of decline in DI across all genetic risk groups. CONCLUSIONS: Individuals with a higher genetic risk for T2D exhibited not only a lower OGTT-derived ß-cell function at baseline but also a notably more rapid decline during follow-up. This information could be used to enable a focused precision prevention with lifestyle intervention.

Genome-Wide Polygenic Risk Score Predicts Incident Type 2 Diabetes in Women With History of Gestational Diabetes.

OBJECTIVE: Women with a history of gestational diabetes mellitus (GDM) are at increased risk of developing type 2 diabetes (T2D). It remains unclear whether genetic information improves prediction of incident T2D in these women. RESEARCH DESIGN AND METHODS: Using five independent cohorts representing four different ancestries (n = 1,895), we investigated whether a genome-wide T2D polygenic risk score (PRS) is associated with increased risk of incident T2D. We also calculated the area under the receiver operating characteristics curve (AUROC) and continuous net reclassification improvement (NRI) following the incorporation of T2D PRS into clinical risk models to assess the diagnostic utility. RESULTS: Among 1,895 women with previous history of GDM, 363 (19.2%) developed T2D in a range of 2 to 30 years. T2D PRS was higher in those who developed T2D (-0.08 vs. 0.31, P = 2.3 × 10-11) and was associated with an increased risk of incident T2D (odds ratio 1.52 per 1-SD increase, 95% CI 1.05-2.21, P = 0.03). In a model that includes age, family history of diabetes, systolic blood pressure, and BMI, the incorporation of PRS led to an increase in AUROC for T2D from 0.71 to 0.74 and an intermediate improvement of NRI (0.32, 95% CI 0.15-0.49, P = 3.0 × 10-4). Although there was variation, a similar trend was observed across study cohorts. CONCLUSIONS: In cohorts of GDM women with diverse ancestry, T2D PRS was significantly associated with future development of T2D. A significant but small improvement was observed in AUROC when T2D PRS was integrated into clinical risk models to predict incident T2D.

Identification of Arabidopsis BAK1-associating receptor-like kinase 1 (BARK1) and characterization of its gene expression and brassinosteroid-regulated root phenotypes.

Brassinosteroids (BRs) activate the BRI1 and BAK1/SERK3 membrane receptor complex, which leads to a wide range of changes in gene expression, plant growth and development. As an initial step to elucidate additional roles of BAK1, we cloned a BAK1-binding protein, BAK1-Associating Receptor-Like Kinase 1 (BARK1), and characterized its gene expression and root phenotypes. BARK1 is a putative membrane LRR-RLK (leucine-rich repeat receptor-like kinase) protein that specifically binds to BAK1 and its homologs. Careful examination of BARK1 expression using transgenic plants expressing a green fluorescent protein (GFP) reporter under the control of the native BARK1 promoter (BARK1p::GFP) revealed that this gene is ubiquitously expressed in most plant tissues, and shows especially strong expression in the xylem vasculature of primary and lateral roots as well as in mature pollen. Interestingly, the expression of the BARK1 gene was increased in the BR biosynthetic loss-of-function mutant, det2, and a loss-of-function mutant of BR signaling, bak1-3. In contrast, this gene was down-regulated in the bzr1-1D plant, which is a BR signal gain-of-function mutant. BARK1-overexpressing transgenic plants clearly enhanced primary root growth in a dose-dependent manner, and their roots were hypersensitive to BR-induced root growth inhibition. In addition, both the number and density of lateral roots were dramatically increased in the BARK1 transgenic plants in a dose-dependent manner. Together with observations that ARF (AUXIN RESPONSE FACTOR) genes are up-regulated in the BARK1 overexpressor, we suggest that the BARK1 overexpressor phenotype with more lateral roots is partly due to the increased expression of ARF genes in this genetic background. In conclusion, BAK1-interacting BARK1 protein may be involved in BR-mediated plant growth and development such as in lateral roots via auxin regulation.

COMP-angiopoietin-1 promotes cavernous angiogenesis in a type 2 diabetic rat model.

Cartilage oligomeric matrix protein-angiopoietin-1 (COMP-Ang1) is an angiogenic factor for vascular angiogenesis. The aim was to investigate the effect of an intracavernosal injection of COMP-Ang1 on cavernosal angiogenesis in a diabetic rat model. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats made up the experimental group (1 yr old) and Long-Evans Tokushima Otsuka (LETO) rats made up the control group. The experimental group was divided into vehicle only, 10 µg COMP-Ang1, and 20 µg COMP-Ang1. COMP-Ang1 was injected into the corpus cavernosum of the penis. After 4 weeks, the penile tissues of the rats were obtained for immunohistochemistry and Western blot analysis. The immunoreactivity of PECAM-1 and VEGF was increased in the COMP-Ang1 group compared with the vehicle only group. Moreover, the expression of PECAM-1 and VEGF was notably augmented in the 20 µg Comp Ang-1 group. In the immunoblotting study, the expression of PECAM-1 and VEGF protein was significantly less in the OLEFT rats than in the control LETO rats. However, this expression was restored to control level after intracavernosal injection of COMP-Ang1. These results show that an intracavernosal injection of COMP-Ang1 enhances cavernous angiogenesis by structurally reinforcing the cavernosal endothelium.

Effects of retinoid-loaded hyaluronic acid nanomicelles on vaginal epithelium in a murine menopause model.

PURPOSE: This study aimed to develop hyaluronic acid (HA)-based, retinoic acid (RA)-containing nanomicelles and to investigate the effects of these newly developed nanomicelles on regeneration of the vaginal epithelium and aquaporin 3 (AQP3) expression in a murine menopause model. MATERIALS AND METHODS: The HA-based, RA-loaded nanomicelles were developed, and the RA-loading rate, encapsulation efficiency, and hydrodynamic diameter were measured. Female BALB/c mice (8 weeks; n=30) were divided into control and experimental groups. Menopause was established in the experimental group by removing both ovaries. The experimental group was further divided into an ovariectomy group, an HA-C18 vehicle group, and an HA-C18-RA group (2.5 µg per mouse); vaginal administration of HA-C18 or HA-C18-RA was performed once daily. After 4 weeks of treatment, murine vaginal tissue was removed, and histological analysis was performed. RESULTS: Three drug-loaded nanomicelles were synthesized: the RA content in HA-C18-RA-10, HA-C18-RA-20, and HA-C18-RA-30 was 3.13%, 2.52%, and 16.67%, respectively, and the RA encapsulation efficiency was 95.57%, 83.92%, and 93.24%, respectively. In the experimental versus control group, serum estrogen levels were significantly reduced, and the vaginal mucosal epithelial layer was significantly thinner. After 4 weeks of treatment, the thickness of the vaginal mucosal epithelial layer and AQP3 expression was increased in the HA-C18-RA group compared with the HA-C18 vehicle group. CONCLUSIONS: The newly developed HA-based nanomicelles containing RA resulted in vaginal epithelial recovery and increased AQP3 expression. The results may contribute to the development of functional vaginal lubricants or moisturizers for the treatment of vaginal dryness.

Different effects of low muscle mass on the risk of non-alcoholic fatty liver disease and hepatic fibrosis in a prospective cohort.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and sarcopenia share insulin resistance as a common pathophysiology and have overlapping clinical manifestation of metabolic derangement; hence, it is difficult to differentiate the independent effect of sarcopenia on the development of NAFLD from concomitant metabolic disorders. Using a community-based prospective cohort study, the contributions of low muscle mass and genetic risk factors to the development of NAFLD and NAFLD-related hepatic fibrosis were investigated in the Korean population. METHODS: This prospective community-based cohort study included 40-70-year-old adults, followed up biennially from 2001-2002 to 2017-2018. NAFLD was defined as a hepatic steatosis index of ≥36, and hepatic fibrosis was defined based on the fibrosis-4 index. Sex-specific quartiles of body mass index (BMI)-adjusted muscle mass were calculated (muscle mass/BMI), and low muscle mass was defined as the lowest quartile (Q1). Cox proportional hazard models for incident NAFLD or hepatic fibrosis incorporating age, sex, BMI of ≥25 kg/m2 , metabolic syndrome and PNPLA3 and TM6SF2 risk alleles were used to assess the independent determinants for incident NAFLD and hepatic fibrosis among individuals with NAFLD at baseline. RESULTS: Among the 4038 participants without NAFLD at baseline (mean age, 51.5 ± 8.8 years), 920 (22.8%) developed NAFLD during the 12-year follow-up period. As muscle mass decreased, the risk of NAFLD increased even after adjustment for age, sex, obesity, metabolic syndrome and PNPLA3 and TM6SF2 risk alleles [hazard ratio (HR) per quartile, 1.18, 95% confidence interval (CI), 1.11-1.27, P < 0.001]. TM6SF2 also affected the risk of NAFLD development [HR 1.19, (95% CI, 1.00-1.40), P = 0.044]. Of the 1176 patients with NAFLD but without hepatic fibrosis at baseline, the incident of hepatic fibrosis was found in 51.8%, 44.7%, 42.6% and 41.0% in Q1, Q2, Q3 and Q4 of BMI-adjusted muscle mass, respectively, during the follow-up period (P for trend = 0.006). However, this trend lost its statistical significance when adjusted for confounders. The PNPLA3 risk variant, but not the TM6SF2 genotype, was an independent risk factor for developing hepatic fibrosis among patients with NAFLD (HR 1.17, 95% CI 1.04-1.32, P = 0.010). CONCLUSIONS: Both lower muscle mass index and genetic risk variants are important contributors to the development of NAFLD. In patients already diagnosed with NAFLD, however, PNPLA3 confers a greater risk for hepatic fibrosis progression than lower muscle mass.

Hydrophobically modified silica nanolaces-armored water-in-oil pickering emulsions with enhanced interfacial attachment energy.

HYPOTHESIS: Anisotropic particles with a high aspect ratio led to favorable interfacial adhesion, thus enabling Pickering emulsion stabilization. Herein, we hypothesized that pearl necklace-shaped colloid particles would play a key role in stabilizing water-in-silicone oil (W/S) emulsions by taking advantage of their enhanced interfacial attachment energy. EXPERIMENTS: We fabricated hydrophobically modified silica nanolaces (SiNLs) by depositing silica onto bacterial cellulose nanofibril templates and subsequently grafting alkyl chains with tuned amounts and chain lengths onto the nanograins comprising the SiNLs. FINDINGS: The SiNLs, of which nanograin has the same dimension and surface chemistry as the silica nanospheres (SiNSs), showed more favorable wettability than SiNSs at the W/S interface, which was supported by the approximately 50 times higher attachment energy theoretically calculated using the hit-and-miss Monte Carlo method. The SiNLs with longer alkyl chains from C6 to C18 more effectively assembled at the W/S interface to produce a fibrillary interfacial membrane with a 10 times higher interfacial modulus, preventing water droplets from coalescing and improving the sedimentation stability and bulk viscoelasticity. These results demonstrate that the SiNLs acted as a promising colloidal surfactant for W/S Pickering emulsion stabilization, thereby allowing the exploration of diverse pharmaceutical and cosmetic formulations.

Earlier Age at Type 2 Diabetes Diagnosis Is Associated With Increased Genetic Risk of Cardiovascular Disease.

OBJECTIVE: We investigated genetic risk of cardiovascular disease (CVD) by age at type 2 diabetes (T2D) diagnosis. RESEARCH DESIGN AND METHODS: We compared incident CVD events by age at T2D diagnosis using UK Biobank (N = 12,321) and the Seoul National University Hospital (SNUH) cohort (N = 1,165). Genetic risk was quantified using polygenic risk score (PRS). RESULTS: Individuals with earlier T2D diagnosis had higher CVD risk. In UK Biobank, the effect size of coronary artery disease (CAD) PRS on incident CAD was largest in individuals diagnosed with T2D at ages 30-39 years (hazard ratio 2.25; 95% CI 1.56-3.26) and decreased as age at diagnosis increased: ages 40-49 (1.51; 1.30-1.75), 50-59 (1.36; 1.24-1.50), and 60-69 years (1.30; 1.14-1.48) (Pinteraction = 0.0031). A similar trend was observed in the SNUH cohort. This increased genetic risk associated with earlier T2D diagnosis was largely mitigated by a healthy lifestyle. CONCLUSIONS: Individuals with an earlier T2D diagnosis have a higher genetic risk of CAD, and this information could be used to tailor lifestyle interventions.

Direct Differentiation of Bone Marrow Mononucleated Cells Into Insulin-Producing Cells Using 4 Specific Soluble Factors.

Bone marrow-derived stem cells are self-renewing and multipotent adult stem cells that differentiate into several types of cells. Here, we investigated a unique combination of 4 differentiation-inducing factors (DIFs), including putrescine (Put), glucosamine (GlcN), nicotinamide, and BP-1-102, to develop a differentiation method for inducing mature insulin-producing cells (IPCs) and apply this method to bone marrow mononucleated cells (BMNCs) isolated from mice. BMNCs, primed with the 4 soluble DIFs, were differentiated into functional IPCs. BMNCs cultured under the defined conditions synergistically expressed multiple genes, including those for PDX1, NKX6.1, MAFA, NEUROG3, GLUT2, and insulin, related to pancreatic beta cell development and function. They produced insulin/C-peptide and PDX1, as assessed using immunofluorescence and flow cytometry. The induced cells secreted insulin in a glucose-responsive manner, similar to normal pancreatic beta cells. Grafting BMNC-derived IPCs under kidney capsules of mice with streptozotocin (STZ)-induced diabetes alleviated hyperglycemia by lowering blood glucose levels, enhancing glucose tolerance, and improving glucose-stimulated insulin secretion. Insulin- and PDX1-expressing cells were observed in the IPC-bearing graft sections of nephrectomized mice. Therefore, this study provides a simple protocol for BMNC differentiation, which can be a novel approach for cell-based therapy in diabetes mellitus.