3D bioprinting of dECM-incorporated hepatocyte spheroid for simultaneous promotion of cell-cell and -ECM interactions

The cell spheroid technology, which greatly enhances cell-cell interactions, has gained significant attention in the development of in vitro liver models. However, existing cell spheroid technologies still have limitations in improving hepatocyte-extracellular matrix (ECM) interaction, which have a significant impact on hepatic function. In this study, we have developed a novel bioprinting technology for decellularized ECM (dECM)-incorporated hepatocyte spheroids that could enhance both cell-cell and -ECM interactions simultaneously. To provide a biomimetic environment, a porcine liver dECM-based cell bio-ink was developed, and a spheroid printing process using this bio-ink was established. As a result, we precisely printed the dECM-incorporated hepatocyte spheroids with a diameter of approximately 160–220 μm using primary mouse hepatocyte (PMHs). The dECM materials were uniformly distributed within the bio-printed spheroids, and even after more than 2 weeks of culture, the spheroids maintained their spherical shape and high viability. The incorporation of dECM also significantly improved the hepatic function of hepatocyte spheroids. Compared to hepatocyte-only spheroids, dECM-incorporated hepatocyte spheroids showed approximately 4.3- and 2.5-fold increased levels of albumin and urea secretion, respectively, and a 2.0-fold increase in CYP enzyme activity. These characteristics were also reflected in the hepatic gene expression levels of ALB, HNF4A, CPS1, and others. Furthermore, the dECM-incorporated hepatocyte spheroids exhibited up to a 1.8-fold enhanced drug responsiveness to representative hepatotoxic drugs such as acetaminophen, celecoxib, and amiodarone. Based on these results, it can be concluded that the dECM-incorporated spheroid printing technology has great potential for the development of highly functional in vitro liver tissue models for drug toxicity assessment

EFFECTS OF WALKING SPEED AND AGE ON THE DIRECTIONAL STRIDE REGULARJRY AND GAIT VARIABILITY IN TREADMILL WALKING

The purpose of this study was to assess the directional stride regularity (SR) and gait variability (GV) of data from shoe-type inertial measurement unit (IMU) sensors during levelled treadmill walking. The DynaStabtm (IMU based gait analysis system) including Smart Balance' (shoe-type data logger) was used to collect normal gait data from forty-four subjects in their 20s (n=20), 40s (n=13), and 60s (n=ll). Four different walking speeds (3, 4, 5, and 6 km/h, respectively) on a treadmill were applied for one-minute of continuous levelled walking. Only lateral kinematics (mediolateral acceleration and yawing and rolling angular velocities) revealed significant interactions from walking speed and age, demonstrating lower stride regularity and higher gait variability than the anteroposterior and vertical kinematics

Commentary on: Incidental Breast Cancers Identified in a One-Stop Symptomatic Breast Clinic

In a recent study published in the Journal of Breast Cancer, Mehrotra et al. [1] reported incidental breast cancers identified in a one-stop symptomatic breast clinic where patients receive the results of their radiological examinations and tissue sampling on the same day. Medical environments differ from country to country and from culture to culture. Nevertheless, breast cancer is the most frequent cancer among women in developed and developing countries [2]. They reported 87.2 % symptomatic cancers and 12.8 % incidental cancers using a definition of symptomatic cancers as “breast cancers correlated to the patient’s symptoms ” and that of incidental cancers as “breast cancers detected only by imaging in a completely separate location to the site of presenting symptoms and not palpable by the clinician. ” In this study, the mean age of patients with symptomatic cancers and incidenta

Comparative Genomics Reveals Adaptation by Alteromonas sp. SN2 to Marine Tidal-Flat Conditions: Cold Tolerance and Aromatic Hydrocarbon Metabolism

Alteromonas species are globally distributed copiotrophic bacteria in marine habitats. Among these, sea-tidal flats are distinctive: undergoing seasonal temperature and oxygen-tension changes, plus periodic exposure to petroleum hydrocarbons. Strain SN2 of the genus Alteromonas was isolated from hydrocarbon-contaminated sea-tidal flat sediment and has been shown to metabolize aromatic hydrocarbons there. Strain SN2's genomic features were analyzed bioinformatically and compared to those of Alteromonas macleodii ecotypes: AltDE and ATCC 27126. Strain SN2's genome differs from that of the other two strains in: size, average nucleotide identity value, tRNA genes, noncoding RNAs, dioxygenase gene content, signal transduction genes, and the degree to which genes collected during the Global Ocean Sampling project are represented. Patterns in genetic characteristics (e.g., GC content, GC skew, Karlin signature, CRISPR gene homology) indicate that strain SN2's genome architecture has been altered via horizontal gene transfer (HGT). Experiments proved that strain SN2 was far more cold tolerant, especially at 5°C, than the other two strains. Consistent with the HGT hypothesis, a total of 15 genomic islands in strain SN2 likely confer ecological fitness traits (especially membrane transport, aromatic hydrocarbon metabolism, and fatty acid biosynthesis) specific to the adaptation of strain SN2 to its seasonally cold sea-tidal flat habitat

Ultra-Fast Displaying Spectral Domain Optical Doppler Tomography System Using a Graphics Processing Unit

We demonstrate an ultrafast displaying Spectral Domain Optical Doppler Tomography system using Graphics Processing Unit (GPU) computing. The calculation of FFT and the Doppler frequency shift is accelerated by the GPU. Our system can display processed OCT and ODT images simultaneously in real time at 120 fps for 1,024 pixels x 512 lateral A-scans. The computing time for the Doppler information was dependent on the size of the moving average window, but with a window size of 32 pixels the ODT computation time is only 8.3 ms, which is comparable to the data acquisition time. Also the phase noise decreases significantly with the window size. Since the performance of a real-time display for OCT/ODT is very important for clinical applications that need immediate diagnosis for screening or biopsy. Intraoperative surgery can take much benefit from the real-time display flow rate information from the technology. Moreover, the GPU is an attractive tool for clinical and commercial systems for functional OCT features as well.open131

Caloric restriction of db/db mice reverts hepatic steatosis and body weight with divergent hepatic metabolism

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver disease and its prevalence is a serious and growing clinical problem. Caloric restriction (CR) is commonly recommended for improvement of obesity-related diseases such as NAFLD. However, the effects of CR on hepatic metabolism remain unknown. We investigated the effects of CR on metabolic dysfunction in the liver of obese diabetic db/db mice. We found that CR of db/db mice reverted insulin resistance, hepatic steatosis, body weight and adiposity to those of db/m mice. H-NMR- and UPLC-QTOF-MS-based metabolite profiling data showed significant metabolic alterations related to lipogenesis, ketogenesis, and inflammation in db/db mice. Moreover, western blot analysis showed that lipogenesis pathway enzymes in the liver of db/db mice were reduced by CR. In addition, CR reversed ketogenesis pathway enzymes and the enhanced autophagy, mitochondrial biogenesis, collagen deposition and endoplasmic reticulum stress in db/db mice. In particular, hepatic inflammation-related proteins including lipocalin-2 in db/db mice were attenuated by CR. Hepatic metabolomic studies yielded multiple pathological mechanisms of NAFLD. Also, these findings showed that CR has a therapeutic effect by attenuating the deleterious effects of obesity and diabetes-induced multiple complications

The earliest known stromatoporoid and its contribution to reef construction

Stromatoporoid-type hypercalcified sponges are known to have contributed to the global reef system since the late Middle Ordovician until their major disappearance in the latest Devonian. However, the timing of their appearance and how the earliest stromatoporoids were incorporated into the reef ecosystem remains a mystery. A stromatoporoid taxon was previously reported from the lower Floian of South China, but this example limitedly occurs within the cryptic space of a lithistid-Calathiumreef and has negligible importance in reef construction, unlike the later stromatoporoids that formed the major reef frameworks during the Palaeozoic. In this study, we describe the earliest known definitive stromatoporoids and the reefs constructed by them in the upper Tremadocian to the lower Floian of South China. The reef framework is dominated by various growth forms of stromatoporoids â ranging from laminar, domical, bulbous to digitate morphologies â that alternate with other organisms such as the calcimicrobe Girvanella and stalked echinoderms. Stromatoporoids have played a significant role in frame-building and binding associated with other reef components, contributing to the construction of a complex reef community similar to those found in the late Middle Ordovician and onwards. In South China, late Cambrian microbial-dominant reefs were rapidly substituted by newly-emerging metazoan reef-builders in the Early Ordovician, such as lithistid sponges, quasi-sponge Calathium, bryozoans, echinoderms, the problematic Pulchrilamina and stromatoporoids. This is in contrast to other palaeocontinents where lithistid-microbial reefs dominated throughout the late Cambrian and Early Ordovician, with Calathium being incor­porated in the Early Ordovician. This finding supports the idea that there was regional heterogeneity in reef evolution during this critical time of the Great Ordovician Biodiversification Event