Invariant natural killer T (iNKT), mucosal-associated invariant T (MAIT), and γδ T cells are innate T cells that acquire memory phenotype in the thymus and share similar biological characteristics. ...However, how their effector differentiation is developmentally regulated is still unclear. Here, we identify analogous effector subsets of these three innate T cell types in the thymus that share transcriptional profiles. Using single-cell RNA sequencing, we show that iNKT, MAIT and γδ T cells mature via shared, branched differentiation rather than linear maturation or TCR-mediated instruction. Simultaneous TCR clonotyping analysis reveals that thymic maturation of all three types is accompanied by clonal selection and expansion. Analyses of mice deficient of TBET, GATA3 or RORγt and additional in vivo experiments corroborate the predicted differentiation paths, while human innate T cells from liver samples display similar features. Collectively, our data indicate that innate T cells share effector differentiation processes in the thymus.
Mesoscopic‐scale stacking reconfigurations are investigated when van der Waals (vdW) films are stacked. A method to visualize complicated stacking structures and mechanical distortions simultaneously ...in stacked atom‐thick films using Raman spectroscopy is developed. In the rigid limit, it is found that the distortions originate from the transfer process, which can be understood through thin film mechanics with a large elastic property mismatch. In contrast, with atomic corrugations, the in‐plane strain fields are more closely correlated with the stacking configuration, highlighting the impact of atomic reconstructions on the mesoscopic scale. It is discovered that the grain boundaries do not have a significant effect while the cracks are causing inhomogeneous strain in stacked polycrystalline films. This result contributes to understanding the local variation of emerging properties from moiré structures and advancing the reliability of stacked vdW material fabrication.
Mesoscopic‐scale stacking reconfigurations and their correlations with mechanical distortions are investigated when van der Waals films are stacked. The origins of deformations are revealed from either the transfer process or the extended impact of atomic reconstructions.
Irisin is a newly identified myokine related to exercise and the browning of white fat. Recently, it was reported that irisin serum levels are associated with intrahepatic triglyceride content, ...suggesting that it might have an important role in the liver. The aim of this study was to determine the role of irisin in hepatocytes. Specifically, the effect of recombinant irisin on palmitic acid (PA)-induced lipogenesis and its related signal pathways were examined in AML12 cells and mouse primary hepatocytes. In the present study, we observed the presence of irisin inside the cells in response to the treatment of recombinant irisin by flow cytometry and cell imaging technique. Recombinant irisin significantly inhibited the PA-induced increase in lipogenic markers ACC and FAS at the mRNA and protein levels, and prevented the PA-induced lipid accumulation in hepatocytes. Additionally, irisin inhibited the PA-induced increase in the expression, nuclear localization, and transcriptional activities of the master regulators of lipogenesis (LXRα and SREBP-1c). Moreover, irisin attenuated PA-induced oxidative stress, which was confirmed by measuring the expression of inflammatory markers (NFκB, COX-2, p38 MAPK, TNF, IL-6) and superoxide indicator (dihydroethidium). The preventive effects of irisin against lipogenesis and oxidative stress were mediated by the inhibition of protein arginine methyltransferase-3 (PRMT3). These findings suggested that irisin might have a beneficial role in the prevention of hepatic steatosis by altering the expression of lipogenic genes and attenuating oxidative stress in a PRMT3 dependent manner.
•The anti-lipogenic role of irisin in palmitic acid-induced steatotic hepatocytes•Palmitic acid-induced oxidative stress lowering effect of irisin•The preventive roles of irisin are dependent on PRMT3.
To prepare for the upcoming big‐data era, numerous attempts are underway to develop a neuromorphic system which is capable of imitating a biologic neural network. Despite the significant improvements ...to software‐based artificial neural networks (ANNs) recently, they remain inefficient in terms of energy use. Alternatively, many researchers have been attracted to hardware‐based ANNs by fundamentally mimicking neural circuits and synapses. In this study, a two‐terminal silicon‐channel synapse (SINAPSE) with a poly‐Si/SiO2/Si3N4 gate stack over a silicon channel is introduced, and demonstrated the smallest size of a synapse device reported thus far, along with reliable, low‐power performance. A distinctive feature of SINAPSE is that it emulates synaptic recovery, a retrieval process for neurotransmitters which would be otherwise depleted. By applying an electrical recovery pulse to SINAPSE, synaptic recovery was for the first time successfully imitated. Experimental results demonstrate the potential of the curable SINAPSE as a fundamental unit in neuromorphic circuitry.
Two‐terminal silicon‐channel synapse device with a poly‐Si/SiO2/Si3N4 gate stack over a silicon channel, named as SINAPSE, dynamically and energy efficiently modulates the channel conductance. Based on the state‐of‐the‐art silicon technology, SINAPSE achieved the smallest synapse device feature size reported so far, and imitated the synaptic recovery behavior of an actual synapse providing a significantly enhanced cyclic endurance characteristic.
We demonstrate all-fiber mode-locked laser based on a tapered optical fiber saturable absorber (SA) enclosed in tungsten disulfide (WS 2 ) nanosheets. Tapered fibers were fabricated using the ...standard flame brushing method to an interaction length of 3 mm with waist diameters of 10 and 15 μm. WS 2 nanosheets were prepared via a liquid phase exfoliation method to form a uniform dispersion. Subsequently, the WS 2 nanosheets were optically deposited along the interaction length of the tapered fibers by evanescent field interactions. We built a ring laser including the fabricated mode-lockers. The SA with a 10-μm taper diameter delivers the pulses with a pulse duration of 369 fs and 3-dB spectral bandwidth of 7.5 nm; on the other hand, the output pulses using the mode-locker with 15-μm waist diameter were found to have 563-fs pulse duration and 5.2 nm of 3-dB bandwidth. It is shown that the smaller waist diameter of tapered fiber causes wider spectral bandwidth of the ultrafast pulses and narrower 3-dB bandwidth.
Gastric cancer remains the leading cause of cancer-related deaths in Northeast Asia. Population-based endoscopic screenings in the region have yielded successful results in early detection of gastric ...tumors. Endoscopic screening rates are continuously increasing, and there is a need for an automatic computerized diagnostic system to reduce the diagnostic burden. In this study, we developed an algorithm to classify gastric epithelial tumors automatically and assessed its performance in a large series of gastric biopsies and its benefits as an assistance tool.
Using 2,434 whole-slide images, we developed an algorithm based on convolutional neural networks to classify a gastric biopsy image into one of three categories: negative for dysplasia (NFD), tubular adenoma, or carcinoma. The performance of the algorithm was evaluated by using 7,440 biopsy specimens collected prospectively. The impact of algorithm-assisted diagnosis was assessed by six pathologists using 150 gastric biopsy cases.
Diagnostic performance evaluated by the AUROC curve in the prospective study was 0.9790 for two-tier classification: negative (NFD) versus positive (all cases except NFD). When limited to epithelial tumors, the sensitivity and specificity were 1.000 and 0.9749. Algorithm-assisted digital image viewer (DV) resulted in 47% reduction in review time per image compared with DV only and 58% decrease to microscopy.
Our algorithm has demonstrated high accuracy in classifying epithelial tumors and its benefits as an assistance tool, which can serve as a potential screening aid system in diagnosing gastric biopsy specimens.
Abstract
Background and Aims
Given that the majority of colorectal cancers (CRCs) develop from high‐risk adenomas, identifying risk factors for high‐risk adenomas is important. The relationship ...between metabolic dysfunction‐associated fatty liver disease (MAFLD) and the risk of colorectal adenoma in young adults remains unclear. We aimed to evaluate this relationship in adults <50 (younger) and ≥50 (older) years of age.
Methods
This cross‐sectional study included 184 792 Korean adults (80% <50 years of age) who all underwent liver ultrasound and colonoscopy. Participants were grouped into those with and without MAFLD and classified by adenoma presence into no adenoma, low‐risk adenoma, or high‐risk adenoma (defined as ≥3 adenomas, any ≥10 mm, or adenoma with high‐grade dysplasia/villous features).
Results
The prevalence of low‐ and high‐risk adenomas among young and older adults was 9.6% and 0.8% and 22.3% and 4.8%, respectively. MAFLD was associated with an increased prevalence of low‐ and high‐risk adenomas in young and older adults. Young adults with MAFLD had a 1.30 (95% CIs 1.26–1.35) and 1.40 (1.23–1.59) times higher prevalence of low‐ and high‐risk adenomas, respectively, compared to those without MAFLD. These associations were consistent even in lean adults (BMI < 23 kg/m
2
) and those without a family history of CRC.
Conclusions
MAFLD is associated with an increased prevalence of low‐ and high‐risk adenomas in Korean adults, regardless of age or obesity status. Whether reducing metabolic risk factors, such as MAFLD, reduces the risk of precancerous lesions and ultimately reduces the risk of early‐onset CRC requires further investigation.
Increased serum levels of immunoglobulin E (IgE) is a risk factor for various diseases, including allergy and anaphylaxis. However, the source and ontogeny of B cells producing IgE under steady state ...conditions are not well defined. Here, we show plasma cells that develop in the thymus and potently secrete IgE and other immunoglobulins, including IgM, IgA, and IgG. The development of these IgE-secreting plasma cells are induced by IL-4 produced by invariant Natural Killer T cells, independent of CD1d-mediated interaction. Single-cell transcriptomics suggest the developmental landscape of thymic B cells, and the thymus supports development of transitional, mature, and memory B cells in addition to plasma cells. Furthermore, thymic plasma cells produce polyclonal antibodies without somatic hypermutation, indicating they develop via the extra-follicular pathway. Physiologically, thymic-derived IgEs increase the number of mast cells in the gut and skin, which correlates with the severity of anaphylaxis. Collectively, we define the ontogeny of thymic plasma cells and show that steady state thymus-derived IgEs regulate mast cell homeostasis, opening up new avenues for studying the genetic causes of allergic disorders.
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