Effect of chitinase- 3- like protein 1 on glucose metabolism: In vitro skeletal muscle and human genetic association study

We investigated the effect of chitinase- 3- like protein 1 (CHI3L1) on glucose metabolism and its underlying mechanisms in skeletal muscle cells, and evaluated whether the observed effects are relevant in humans. CHI3L1 was associated with increased glucose uptake in skeletal muscles in an AMP- activated protein kinase (AMPK)- dependent manner, and with increased intracellular calcium levels via PAR2. The improvement in glucose metabolism observed in an intraperitoneal glucose tolerance test on male C57BL/6J mice supported this association. Inhibition of the CaMKK was associated with suppression of CHI3L1- mediated glucose uptake. Additionally, CHI3L1 was found to influence glucose uptake through the PI3K/AKT pathway. Results suggested that CHI3L1 stimulated the phosphorylation of AS160 and p38 MAPK downstream of AMPK and AKT, and the resultant GLUT4 translocation. In primary myoblast cells, stimulation of AMPK and AKT was observed in response to CHI3L1, underscoring the biological relevance of CHI3L1. CHI3L1 levels were elevated in cells under conditions that mimic exercise in vitro and in exercised mice in vivo, indicating that CHI3L1 is secreted during muscle contraction. Finally, similar associations between CHI3L1 and metabolic parameters were observed in humans alongside genotype associations between CHI3L1 and diabetes at the population level. CHI3L1 may be a potential therapeutic target for the treatment of diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162777/2/fsb220907.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162777/1/fsb220907_am.pd

Single-Cell Profiling Reveals Inflammatory Polarization of Human Carotid Versus Femoral Plaque Leukocytes

Femoral atherosclerotic plaques are less inflammatory than carotid plaques histologically, but limited cell-level data exist regarding comparative immune landscapes and polarization at these sites. We investigated intraplaque leukocyte phenotypes and transcriptional polarization in 49 patients undergoing femoral (n = 23) or carotid (n = 26) endarterectomy using single-cell RNA-Seq (scRNA-Seq; n = 13), flow cytometry (n = 24), and IHC (n = 12). Comparative scRNA-Seq of CD45+-selected leukocytes from femoral (n = 9; 35,265 cells) and carotid (n = 4; 30,655 cells) plaque revealed distinct transcriptional profiles. Inflammatory foam cell-like macrophages and monocytes comprised higher proportions of myeloid cells in carotid plaques, whereas noninflammatory foam cell-like macrophages and LYVE1-overexpressing macrophages comprised higher proportions of myeloid cells in femoral plaque (P \u3c 0.001 for all). A significant comparative excess of CCR2+ macrophages in carotid versus plaque was observed by flow cytometry in a separate validation cohort. B cells were more prevalent and exhibited a comparatively antiinflammatory profile in femoral plaque, whereas cytotoxic CD8+ T cells were more prevalent in carotid plaque. In conclusion, human femoral plaques exhibit distinct macrophage phenotypic and transcriptional profiles as well as diminished CD8+ T cell populations compared with human carotid plaques

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Pull-Out Resistance of Rebar Stake Depending on Installation Conditions and Compaction Levels of Agricultural Soil

Strong winds, particularly in the absence of disaster-resistant designs, significantly impact the stability of greenhouse foundations and eventually lead to structural damage and potential harm to crops. As a countermeasure, rebar stakes are commonly used to reinforce the foundations of non-disaster-resistant greenhouses. This study evaluates the pull-out resistance (Rpull-out) of rebar stakes considering various factors like soil compaction, embedded length, installation duration and angle, and changes in soil water content against uplift pressure by strong winds. A combination of field (i.e., the cone penetration test and rebar stake pull-out test) and laboratory (i.e., the compaction test, soil compaction meter test, and soil box test) tests are performed for the assessment of Rpull-out. The results indicate that Rpull-out increases with higher soil compaction, greater embedded length, longer installation duration, and an inclined installation angle. The soil compaction exerts the most significant impact; 90% to 100% of the soil compaction rate has approximately 10 folds higher Rpull-out than the 60–70% compaction rate. If the embedded length is increased from 20 cm to 40 cm, there is a two-fold increase in the average of Rpull-out. Inclined installation of rebar stakes increases Rpull-out by 250% to 350% compared to vertical installation, and rebar stakes installed prior to the uplift event have 1.5 to 6.4 fold increases in Rpull-out than those with instant installation. Additionally, we observed variations in the surface soil moisture due to climatic changes introducing variability in Rpull-out. These findings lead to the proposition of efficient rebar stake installation methods, contributing to the enhanced stability of a greenhouse

Current Status of Anti-Reflux Surgery as a Treatment for GERD

Anti-reflux surgery (ARS) is an efficient treatment option for gastroesophageal reflux disease (GERD). Despite growing evidence of the efficacy and safety of ARS, medications including proton pump inhibitors (PPIs) remain the most commonly administered treatments for GERD. Meanwhile, ARS can be an effective treatment option for patients who need medications continuously or for those who are refractory to PPI treatment, if proper candidates are selected. However, in practice, ARS is often regarded as a last resort for patients who are unresponsive to PPIs. Accumulating ARS-related studies indicate that surgery is equivalent to or better than medical treatment for controlling typical and atypical GERD symptoms. Furthermore, because of overall reduced medication expenses, ARS may be more cost-effective than PPI. Patients are selected for ARS based on endoscopic findings, esophageal acid exposure time, and PPI responsiveness. Although there is limited evidence, ARS may be expanded to include patients with normal acid exposure, such as those with reflux hypersensitivity. Additionally, other factors such as age, body mass index, and comorbidities are known to affect ARS outcomes; and such factors should be considered. Nissen fundoplication or partial fundoplication including Dor fundoplication and Toupet fundoplication can be chosen, depending on whether the patient prioritizes symptom improvement or minimizing postoperative symptoms such as dysphagia. Furthermore, efforts to reduce and manage postoperative complications and create awareness of the long-term efficacy and safety of the ARS are recommended, as well as adequate training programs for new surgeons

Development of an assessment method for freely moving nonhuman primates’ eating behavior using manual and deep learning analysis

Purpose: Although eating is imperative for survival, few comprehensive methods have been developed to assess freely moving nonhuman primates' eating behavior. In the current study, we distinguished eating behavior into appetitive and consummatory phases and developed nine indices to study them using manual and deep learning-based (DeepLabCut) techniques. Method: The indices were utilized to three rhesus macaques by different palatability and hunger levels to validate their utility. To execute the experiment, we designed the eating behavior cage and manufactured the artificial food. The total number of trials was 3, with 1 trial conducted using natural food and 2 trials using artificial food. Result: As a result, the indices of highest utility for hunger effect were approach frequency and consummatory duration. Appetitive composite score and consummatory duration showed the highest utility for palatability effect. To elucidate the effects of hunger and palatability, we developed 2D visualization plots based on manual indices. These 2D visualization methods could intuitively depict the palatability perception and hunger internal state. Furthermore, the developed deep learning-based analysis proved accurate and comparable with manual analysis. When comparing the time required for analysis, deep learning-based analysis was 24-times faster than manual analysis. Moreover, temporal and spatial dynamics were visualized via manual and deep learning-based analysis. Based on temporal dynamics analysis, the patterns were classified into four categories: early decline, steady decline, mid-peak with early incline, and late decline. Heatmap of spatial dynamics and trajectory-related visualization could elucidate a consumption posture and a higher spatial occupancy of food zone in hunger and with palatable food. Discussion: Collectively, this study describes a newly developed and validated multi-phase method for assessing freely moving nonhuman primate eating behavior using manual and deep learning-based analyses. These effective tools will prove valuable in food reward (palatability effect) and homeostasis (hunger effect) research

Deep learning-based retrieval of cyanobacteria pigment in inland water for in-situ and airborne hyperspectral data

Worldwide proliferation of cyanobacteria blooms in inland waters not only affects the intended use of water but potentially threatens human and animal health. In this study, a stacked autoencoder-deep neural network (SAE-DNN) was developed to estimate phycocyanin (PC) concentration by using in situ reflectance spectra in productive inland water. The estimated PC using the SAE-DNN was in close agreement with the measured PC, with an R2 of 0.87, root mean square error (RMSE) of 14.45?????g/L, and relative RMSE of 86.42%. The performance of the SAE-DNN was superior to that of the DNN and band-ratio algorithms. An analysis on the deep spectral features extracted using the SAE yielded the most useful spectral bands, namely 538, 596, and 735???nm, for the retrieval of PC. The estimation accuracy of the SAE-DNNPeaks, using only the aforementioned spectral bands as input variables, was comparable to that of the SAE-DNN, demonstrating that the high-level of abstraction using the SAE facilitated the improvement in feature learning. The application of the SAE-DNNPeaks to airborne hyperspectral image data resulted in an acceptable estimation accuracy, despite a bias toward underestimation, potentially arising from uncertainty associated with atmospheric correction, at high PC concentrations. Our results suggest that simple, empirical-based approaches, such as the SAE-DNNPeaks, have the potential to serve as a rapid assessment tool for the abundance and spatial distribution of cyanobacteria