Insulin resistance as a hallmark of type 2 DM (T2DM) plays a role in dementia by promoting pathological lesions or enhancing the vulnerability of the brain. Numerous studies related to ...insulin/insulin-like growth factor 1 (IGF-1) signaling are linked with various types of dementia. Brain insulin resistance in dementia is linked to disturbances in Aβ production and clearance, Tau hyperphosphorylation, microglial activation causing increased neuroinflammation, and the breakdown of tight junctions in the blood-brain barrier (BBB). These mechanisms have been studied primarily in Alzheimer's disease (AD), but research on other forms of dementia like vascular dementia (VaD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) has also explored overlapping mechanisms. Researchers are currently trying to repurpose anti-diabetic drugs to treat dementia, which are dominated by insulin sensitizers and insulin substrates. Although it seems promising and feasible, none of the trials have succeeded in ameliorating cognitive decline in late-onset dementia. We highlight the possibility of repositioning anti-diabetic drugs as a strategy for dementia therapy by reflecting on current and previous clinical trials. We also describe the molecular perspectives of various types of dementia through the insulin/IGF-1 signaling pathway.
To investigate the CGE on hair growth and to explore the mechanism that is involved in the acceleration of anagen induction, we investigated the effects of CGE studied on cell proliferation and ...molecular mechanism in human hair dermal papilla cells (hDPCs) and keratinocytes (HaCaT cells). Additionally, hair growth evaluation was carried out following topical treatment of the dorsal skin of telogen C57BL/6 mice with CGE for 14 days. As result, CGE increased cell viability and ALP activity in hDPCs. Moreover, CGE increased the expression of catenin beta 1 (CTNNB1), ALP, sex-determining region Y-box 2 (SOX2), insulin-like growth factor 1 (IGF1), and vascular endothelial growth factor A (VEGFA) genes in hDPCs. CGE increased the expression of proteins such as ALP, β-catenin, and phosphorylation of glycogen synthase kinase 3β (pGSK3β), and protein kinase B (pAKT) in hDPCs. Furthermore, CGE induced the proliferation of HaCaT cells and up-regulated AKT-ERK-GSKβ-β-catenin signaling in HaCaT cells. Additionally, the anagen induction effects of CGE were confirmed on the telogen-anagen transition mice model. these findings demonstrated that CGE promoted the entering the growth phase of hair follicle via activation of β-catenin signaling pathways in vivo. Thus, this study suggests that CGE might be a potential therapeutic reagent for hair growth.
A bioinspired neuromorphic device operating as synapse and neuron simultaneously, which is fabricated on an electrolyte based on Cu2+‐doped salmon deoxyribonucleic acid (S‐DNA) is reported. Owing to ...the slow Cu2+ diffusion through the base pairing sites in the S‐DNA electrolyte, the synaptic operation of the S‐DNA device features special long‐term plasticity with negative and positive nonlinearity values for potentiation and depression (αp and αd), respectively, which consequently improves the learning/recognition efficiency of S‐DNA‐based neural networks. Furthermore, the representative neuronal operation, “integrate‐and‐fire,” is successfully emulated in this device by adjusting the duration time of the input voltage stimulus. In particular, by applying a Cu2+ doping technique to the S‐DNA neuromorphic device, the characteristics for synaptic weight updating are enhanced (|αp|: 31→20, |αd|: 11→18, weight update margin: 33→287 nS) and also the threshold conditions for neuronal firing (amplitude and number of stimulus pulses) are modulated. The improved synaptic characteristics consequently increase the Modified National Institute of Standards and Technology (MNIST) pattern recognition rate from 38% to 44% (single‐layer perceptron model) and from 89.42% to 91.61% (multilayer perceptron model). This neuromorphic device technology based on S‐DNA is expected to contribute to the successful implementation of a future neuromorphic system that simultaneously satisfies high integration density and remarkable recognition accuracy.
A bioinspired neuromorphic device operating as synapse and neuron simultaneously is fabricated on an electrolyte based on Cu2+‐doped salmon deoxyribonucleic acid (S‐DNA). The special long‐term pasticity of this S‐DNA neuromorphic device improves the learning/recognition accuracy of S‐DNA‐based neural networks from 38 to 44% (single‐layer perceptron model) and from 89.42 to 91.61% (multi‐layer perceptron model).
Objectives
To investigate the performance of the Liver Imaging Reporting and Data System (LI-RADS) v2017 for combined hepatocellular cholangiocarcinoma (cHCC-CCA) in the differential diagnosis from ...hepatocellular carcinoma (HCC) and prediction of prognosis on gadoxetic acid-enhanced MRI (Gd-EOB-MRI).
Methods
Patients at high risk of HCC with pathologically confirmed cHCC-CCAs (
n
= 70) and a matched control of HCCs (
n
= 70) who had undergone Gd-EOB-MRI were included. LI-RADS category was assigned for each lesion by two radiologists. Imaging features and surgical outcomes were compared between cHCC-CCAs of LR-M and LR-5/4 using the χ
2
test or Fisher’s exact test. Recurrence-free survival (RFS) was estimated using Kaplan–Meier survival curves and compared using the log-rank test.
Results
cHCC-CCAs and HCCs were categorised as LR-M, LR-5/4 and LR-TIV in 61.4% (43/70), 37.1% (26/70) and 1.4% (1/70) and 10.0% (7/70), 88.6% (62/70) and 1.4% (1/70), respectively. cHCC-CCAs of LR-5/4, in comparison to LR-M, showed significantly higher frequencies of major HCC features: arterial hyperenhancement (96.2% (25/26) vs. 58.1% (25/43),
p
= 0.001), washout appearance (80.8% (21/26) vs. 48.8% (21/43),
p
= 0.011) and enhancing capsule (34.6% (9/26) vs. 11.6% (5/43),
p
= 0.031). After curative surgery, patients with cHCC-CCAs of LR-M showed a higher early recurrence rate (≤ 6 months) than did those with LR-5/4 (27.8% (10/36) vs. 4.8% (1/21),
p
= 0.041), whereas no significant difference was observed in RFS (log-rank
p
= 0.084).
Conclusions
By using LI-RADS on Gd-EOB-MRI, a substantial proportion of cHCC-CCAs can be categorised as non-LR-M. In addition, cHCC-CCAs mimicking HCCs on imaging (LR-5/4) may indicate better surgical outcomes with regard to early recurrence than those of LR-M.
Key Points
• cHCC-CCAs can be categorised as either LR-M or non-LR-M on Gd-EOB-MRI.
• cHCC-CCAs of LR-5/4 frequently demonstrate major HCC imaging features.
• LI-RADS categorisation may provide prognostic information after surgery in cHCC-CCAs.
We aimed (1) to clarify difference in the natural history of lumbar spinal stenosis (LSS) with respect to surgical treatment according to severity of stenosis on magnetic resonance imaging (MRI) ...using qualitative grading system and (2) to estimate surgical probabilities depending on radiological severity.
With the design of retrospective observational study, a total of 1,248 patients diagnosed with LSS between 2011 and 2014 at our hospital were followed up for the mean duration of 7.7 years (5.17-9.8 years). We investigated severity of central and foraminal stenoses on initial MRI using qualitative grading system and whether surgical treatment was performed. Logistic regression models were used to identify risk factors for surgery.
During the mean follow-up period of 7.7 years, grade 3 maximal central stenosis showed the highest percentage of surgical treatment (57.9%-62.3%) with no significant difference in surgical probabilities according to concomitant foraminal stenosis. Surgical probabilities in grade 2 and 3 maximal foraminal stenosis, were 22.2%-62.3% and 33.3%-57.9%, respectively, depending on concomitant central stenosis. Maximal central stenosis of grades 1, 2, and 3 (odds ratio OR: 1.79, 2.21, and 6.26, respectively), and maximal foraminal stenosis of grades 2 and 3 (OR: 2.22 and 2.12, respectively) were significant risk factors for surgical treatment.
The high grades of maximal central and foraminal stenoses were risk factors for surgical treatment. Surgical probabilities were 57.9%-62.3% in grade 3 maximal central stenosis, 22.2%-62.3% and 33.3%-57.9%, respectively, in grade 2 and 3 maximal foraminal stenosis during the mean follow-up period of 7.7 years. These results indicate that the natural history of LSS differs according to grade of maximal central and foraminal stenoses.
Sensory neuromorphic systems are a promising technology, because they can replicate the way the human peripheral nervous system processes signals from the five sensory organs. Despite this potential, ...there are limited studies on how to implement these systems on a hardware neural network platform. In our research, we propose a tactile neuromorphic system that uses a poly(dimethylsiloxane) (PDMS)-based triboelectric sensor and a molybdenum disulfide (MoS2)/poly(vinylidene fluoride-trifluoro ethylene) (P(VDF-TrFE)) heterostructure-based ferroelectric synapse. The triboelectric sensor mimics a human tactile organ by converting tactile stimuli into electrical signals in real time. The ferroelectric synapse we developed demonstrates exceptional long-term potentiation/depression characteristics with a maximum dynamic range of 78 and a symmetrical value of 4.7. To assess the practicality of our proposed system, we conducted training and recognition simulations using Morse code alphabets and MNIST handwritten digits. The maximum recognition rate that we achieved was 96.17%.
Modern gas turbines have evolved by increasing the turbine inlet temperature (TIT) to improve performance. This development has led to a demand for cooling techniques. Among these, the film cooling, ...which involves injecting compressed air through holes on the turbine surface, is a prominent cooling technique used to protect the turbine surface. In this study, a comparative analysis is conducted between the conventional fan-shaped film cooling hole, primarily used in film cooling techniques, and modified shapes achieved by altering the geometry of the film cooling hole based on a fan-shaped hole to assess and compare the cooling performance on a flat plate surface. The adiabatic film cooling effectiveness was measured for three film cooling holes, the Baseline of a 7-7-7 fan-shaped film cooling hole, namely, Staircase, which had a double-step at the hole exit, and Compound Expansion, which had an additional expanded flow path at the hole leading edge. The used measurement technique was the pressure-sensitive paint (PSP) technique, using nitrogen gas as the foreign gas, and experiments were conducted at a density ratio of 1.0 and blowing ratios ranging from 0.5 to 2.0. The results reveal that the modified holes featured wider lateral expansion at the hole exits, resulting in a broader distribution of the cooling effectiveness in the lateral direction compared to the Baseline. The Staircase shows a better performance, although an overall cooling effectiveness trend similar to that of the Baseline. Furthermore, the Compound Expansion demonstrates an enhancement in the cooling performance with an increased blowing ratio, notably achieving nearly double the cooling effectiveness compared to that of the Baseline at a blowing ratio of 2.0.
In recent years when the demand for high-performance biosensors has been aroused, a field-effect transistor (FET)-type biosensor (BioFET) has attracted great interest because of its high sensitivity, ...label-free detection, fast detection speed, and miniaturization. However, the insulating membrane in the conventional BioFET, which is essential in preventing the surface dangling bonds of typical semiconductors from nonspecific bindings, has limited the sensitivity of biosensors. Here, we present a highly sensitive and reusable membraneless BioFET based on a defect-free van der Waals material, tungsten diselenide (WSe2). We intentionally generated a few surface defects that serve as extra binding sites for the bioreceptor immobilization through weak oxygen plasma treatment, consequently magnifying the sensitivity values to 2.87 × 105 A/A for 10 mM glucose. The WSe2 BioFET also maintained its high sensitivity even after several cycles of rinsing and glucose application were repeated.
Several studies have previously been conducted to improve the cooling performance of film cooling. However, most of the research has conducted experiments with film cooling holes on flat plates, and ...thus, the results of these studies do not encompass the influence of the complex mainstream behavior within the turbine passage on film cooling. In this study, three different film cooling hole configurations were installed on the endwall of a turbine linear cascade to measure adiabatic film cooling effectiveness and evaluate cooling performance. The film cooling holes compared in the experiment for film cooling effectiveness were a 7-7-7 fan-shaped hole (Baseline), a Baseline with a double-step structure at the hole exit (Staircase), and a Baseline with an additional expanded passage at the hole leading edge (Compound Expansion). A total of nine holes were manufactured on the turbine endwall to assess film cooling performance, as various factors, such as mainstream acceleration, secondary flow within the turbine passage, and so on, can influence film cooling. Adiabatic film cooling effectiveness was measured using the pressure-sensitive paint (PSP) technique. Mass flow ratios ranging from 0.25% to 1.25% of the mass flow rate of a single turbine passage were supplied to the plenum chamber within the test rig. As a result, all experimental results confirmed the impact of secondary flow within the turbine passage on film cooling. In the case of the Staircase, it exhibits an overall cooling trend similar to the Baseline. It shows small cooling performance degradation compared with Baseline due to lift-off, and its double-step structure laterally expanding results in better cooling performance at high mass flow ratio (MFR) conditions. For the Compound Expansion, at low MFR, the momentum of the coolant is lower compared with other configurations, leading to lower cooling performance due to the influence of secondary flow. However, at high MFR, the Compound Expansion provides wider protection compared with other hole geometries and shows high cooling performance.
Sarcopenia has been defined as a progressive decline of skeletal muscle mass, strength, and functions in elderly people. It is accompanied by physical frailty, functional disability, falls, ...hospitalization, and mortality, and is becoming a major geriatric disorder owing to the increasing life expectancy and growing older population worldwide. Experimental models are critical to understand the pathophysiology of sarcopenia and develop therapeutic strategies. Although its etiologies remain to be further elucidated, several mechanisms of sarcopenia have been identified, including cellular senescence, proteostasis imbalance, oxidative stress, and "inflammaging." In this article, we address three main aspects. First, we describe the fundamental aging mechanisms. Next, we discuss both in vitro and in vivo experimental models based on molecular mechanisms that have the potential to elucidate the biochemical processes integral to sarcopenia. The use of appropriate models to reflect sarcopenia and/or its underlying pathways will enable researchers to understand sarcopenia and develop novel therapeutic strategies for sarcopenia. Lastly, we discuss the possible molecular targets and the current status of drug candidates for sarcopenia treatment. In conclusion, the development of experimental models for sarcopenia is essential to discover molecular targets that are valuable as biochemical biomarkers and/or therapeutic targets for sarcopenia.
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