Crosslinking-induced anion transport control for enhancing linearity in organic synaptic devices.

Numerous studies on neuromorphic computing systems and their associated synaptic devices have been reported for the efficient processing of complex data. Among them, organic electrochemical transistors (OECTs) have attracted considerable attention owing to their advantages such as low cost, high scalability, and facile electrical modulation. However, the requirement of supplementary processing for ionic transport control to actualize or enhance synaptic attributes necessitates a compromise between their inherent benefits. Here, we developed a simple method, photoinduced crosslinking, which can control the structure of conjugated polymers in OECTs to improve ionic transport control. Crosslinked polymers increase the ion doping efficiency and allow sequential anion movements, which leads to high linearity in OECTs. The fabricated device also exhibited enhanced synaptic properties such as a long retention time, wide dynamic range, and high recognition accuracy. This innovative approach opens up new possibilities for the construction of next-generation artificial synapses.

Multi-scaled temporal modeling of cardiovascular disease progression: An illustration of proximal arteries in pulmonary hypertension.

The progression of cardiovascular disease is intricately influenced by a complex interplay between physiological pathways, biochemical processes, and physical mechanisms. This study aimed to develop an in-silico physics-based approach to comprehensively model the multifaceted vascular pathophysiological adaptations. This approach focused on capturing the progression of proximal pulmonary arterial hypertension, which is significantly associated with the irreversible degradation of arterial walls and compensatory stress-induced growth and remodeling. This study incorporated critical characteristics related to the distinct time scales for the deformation, thus reflecting the impact of mean pressure on artery growth and tissue damage. The in-silico simulation of the progression of pulmonary hypertension was realized based on computational code combined with the finite element method (FEM) for the simulation of disease progression. The parametric studies further explored the consequences of these irreversible processes. This computational modeling approach may advance our understanding of pulmonary hypertension and its progression.

Unveiling the Role of Side Chain for Improving Nonvolatile Characteristics of Conjugated Polymers-Based Artificial Synapse.

Interest has grown in services that consume a significant amount of energy, such as large language models (LLMs), and research is being conducted worldwide on synaptic devices for neuromorphic hardware. However, various complex processes are problematic for the implementation of synaptic properties. Here, synaptic characteristics are implemented through a novel method, namely side chain control of conjugated polymers. The developed devices exhibit the characteristics of the biological brain, especially spike-timing-dependent plasticity (STDP), high-pass filtering, and long-term potentiation/depression (LTP/D). Moreover, the fabricated synaptic devices show enhanced nonvolatile characteristics, such as long retention time (≈102 s), high ratio of Gmax/Gmin, high linearity, and reliable cyclic endurance (≈103 pulses). This study presents a new pathway for next-generation neuromorphic computing by modulating conjugated polymers with side chain control, thereby achieving high-performance synaptic properties.

Regulation of Betaine Homocysteine Methyltransferase by Liver Receptor Homolog-1 in the Methionine Cycle.

Betaine-homocysteine S-methyltransferase (BHMT) is one of the most abundant proteins in the liver and regulates homocysteine metabolism. However, the molecular mechanisms underlying Bhmt transcription have not yet been elucidated. This study aimed to assess the molecular mechanisms underlying Bhmt transcription and the effect of BHMT deficiency on metabolic functions in the liver mediated by liver receptor homolog-1 (LRH-1). During fasting, both Bhmt and Lrh-1 expression increased in the liver of Lrh-1f/f mice; however, Bhmt expression was decreased in LRH-1 liver specific knockout mice. Promoter activity analysis confirmed that LRH-1 binds to a specific site in the Bhmt promoter region. LRH-1 deficiency was associated with elevated production of reactive oxygen species (ROS), lipid peroxidation, and mitochondrial stress in hepatocytes, contributing to hepatic triglyceride (TG) accumulation. In conclusion, this study suggests that the absence of an LRH-1-mediated decrease in Bhmt expression promotes TG accumulation by increasing ROS levels and inducing mitochondrial stress. Therefore, LRH-1 deficiency not only leads to excess ROS production and mitochondrial stress in hepatocytes, but also disrupts the methionine cycle. Understanding these regulatory pathways may pave the way for novel therapeutic interventions against metabolic disorders associated with hepatic lipid accumulation.

Loss of SREBP-1c ameliorates iron-induced liver fibrosis by decreasing lipocalin-2.

Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression. Wild-type and SREBP-1c knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl4), and subjected to lipocalin-2 (LCN2) overexpression. The role of LCN2 in NASH progression was assessed using mouse primary hepatocytes, Kupffer cells, and HSCs. LCN2 expression was examined in samples from normal patients and those with NASH. LCN2 gene expression and secretion increased in CCl4-induced liver fibrosis mice model, and SREBP-1c regulated LCN2 gene transcription. Moreover, treatment with holo-LCN2 stimulated intracellular iron accumulation and fibrosis-related gene expression in mouse primary HSCs, but these effects were not observed in 1cKO HSCs, indicating that SREBP-1c-induced LCN2 expression and secretion could stimulate HSCs activation through iron accumulation. Furthermore, LCN2 expression was strongly correlated with inflammation and fibrosis in patients with NASH. Our findings indicate that SREBP-1c regulates Lcn2 gene expression, contributing to diet-induced NASH. Reduced Lcn2 expression in 1cKO mice protects against NASH development. Therefore, the activation of Lcn2 by SREBP-1c establishes a new connection between iron and lipid metabolism, affecting inflammation and HSCs activation. These findings may lead to new therapeutic strategies for NASH.

Monolithic DNApatite: An Elastic Apatite with Sub-Nanometer Scale Organo-Inorganic Structures.

Hydroxyapatite (HA) exhibits outstanding biocompatibility, bioactivity, osteoconductivity, and natural anti-inflammatory properties. Pure HA, ion-doped HA, and HA-polymer composites are investigated, but critical limitations such as brittleness remain; numerous efforts are being made to address them. Herein, the novel self-crystallization of a polymeric single-stranded deoxyribonucleic acid (ssDNA) without additional phosphate ions for synthesizing deoxyribonucleic apatite (DNApatite) is presented. The synthesized DNApatite, DNA1Ca2.2(PO4)1.3OH2.1, has a repetitive dual phase of inorganic HA crystals and amorphous organic ssDNA at the sub-nm scale, forming nanorods. Its mechanical properties, including toughness and elasticity, are significantly enhanced compared with those of HA nanorod, with a Young's modulus similar to that of natural bone.

Bedside prediction of right subclavian venous catheter insertion length / Previsão do comprimento de inserção de cateter em veia subclávia direita à beira do leito / Previsión a pie de cama de la extensión de inserción de catéter en vena subclavia derecha

Background and objective: The present study aimed to evaluate whether right subclavian vein (SCV) catheter insertion depth can be predicted reliably by the distances from the SCV insertion site to the ipsilateral clavicular notch directly (denoted as I-IC), via the top of the SCV arch, or via the clavicle (denoted as I-T-IC and I-C-IC, respectively). Method: In total, 70 SCV catheterizations were studied. The I-IC, I-T-IC, and I-C-IC distances in each case were measured after ultrasound-guided SCV catheter insertion. The actual length of the catheter between the insertion site and the ipsilateral clavicular notch, denoted as L, was calculated by using chest X-ray. Results: L differed from the I-T-IC, I-C-IC, and I-IC distances by 0.14±0.53, 2.19±1.17, and -0.45 ±0.68 cm, respectively. The mean I-T-IC distance was the most similar to the mean L (intraclass correlation coefficient = 0.89). The mean I-IC was significantly shorter than L, while the mean I-C-IC was significantly longer. Linear regression analysis provided the following formula: Predicted SCV catheter insertion length (cm) = -0.037 + 0.036 × Height (cm) + 0.903 × I-T-IC (cm) (adjusted r2 =0.64). Conclusion: The I-T-IC distance may be a reliable bedside predictor of the optimal insertion length for a right SCV cannulation. .

Justificativa e objetivo: O presente estudo teve como objetivo avaliar se a profundidade de inserção de cateter em veia subclávia (VSC) direita pode ser prevista de forma confiável pelas distâncias do local de inserção na VSC até a incisura clavicular ipsilateral (I-IC), passando diretamente pela parte superior do arco da VSC ou da clavícula (denominadas i-T-IC e i-C-IC, respectivamente). Método: No total, 70 cateterismos de VSC foram estudados. As distâncias I-IC, I-T-IC e I-C-IC de cada caso foram mensuradas após a inserção do cateter guiada por ultrassom. O comprimento do cateter entre o local de inserção e a incisura clavicular ipsilateral (L) foi calculado por meio de radiografia. Resultados: As diferenças em centímetros de L em relação às distâncias I-T-IC, I-C-IC e I-IC foram de 0,14±0,53; 2,19±1,17 e 0,45±0,68 respectivamente. A média de I-IC foi significativamente menor que L, enquanto a média de I-C-IC foi significativamente maior. A análise de regressão linear forneceu a seguinte fórmula: Comprimento previsto da inserção de cateter em VSC (cm) = -0,037 + 0,036 × Altura (cm) + 0,903 × I-T-IC (cm) (r2 ajustado = 0,64). Conclusão: A distância I-T-IC pode ser um preditivo confiável do comprimento de inserção ideal para canulação em VSC direita. .

Introducción y objetivo: El presente estudio tuvo como objetivo evaluar si la profundidad de inserción de catéter en vena subclavia (VSC) derecha puede ser prevista de forma confiable por las distancias del lugar de inserción en la VSC hasta la incisión clavicular ipsilateral (denominada I-IC), pasando directamente por la parte superior del arco de la VSC o de la clavícula (denominadas I-T-IC y I-C-IC, respectivamente). Método: En total se estudiaron 70 cateterismos de VSC. Las distancias I-IC, I-T-IC e I-C-IC de cada caso fueron medidas después de la inserción del catéter guiada por ultrasonido. La extensión del catéter entre la región de inserción y la incisión clavicular ipsilateral, denominada L, fue calculada por medio de radiografía. Resultados: Las diferencias en centímetros de L con relación a las distancias I-I- IC, I-C-IC e I-IC fueron de 0,14±0,53, 2,19±1,17 y 0,45±0,68, respectivamente. La media de I-IC fue significativamente menor que L, mientras que la media de I-C-IC fue significativamente mayor. El análisis de regresión linear suministró la siguiente fórmula: Extensión prevista de la inserción de catéter en VSC (cm) = -0,037 + 0,036 × altura (cm) + 0,903 × I-T-IC (cm) (r2 ajustado = 0,64). Conclusión: La distancia I-T-IC puede ser un predictor confiable de la extensión de la inserción ideal para la canalización en la VSC derecha. .