AAD-2004, a potent spin trapping molecule and microsomal prostaglandin E synthase-1 inhibitor, shows safety and efficacy in a mouse model of ALS

While free radicals and inflammation constitute major routes of neuronal injury occurring in neurodegenerative diseases, neither antioxidants nor nonsteroidal anti-inflammatory drugs (NSAIDs) have shown significant efficacy in human clinical trials. To explore the possibility that concurrent blockade of free radicals and PGE2-mediated inflammation might constitute a safe and effective therapeutic approach to certain neurodegenerative diseases, we have developed 2-hydroxy-5-[2-(4-trifluoromethylphenyl)-ethylaminobezoic acid (AAD-2004) as a derivative of aspirin. AAD-2004 completely removed free radicals at 50 nM as a potent spin trapping molecule and inhibited microsomal prostaglandin E synthase-1 (mPGES-1) with an IC50 of 230 nM. Oral administration of AAD-2004 blocked free radical formation, PGE2 formation, and microglial activation in the spinal motor neurons of SOD1G93A mice. As a consequence, AAD-2004 reduced autophagosome formation, axonopathy, and motor neuron degeneration, improving motor function and increasing life span. In these assays, AAD-2004 was superior to ibuprofen or riluzole. Gastric bleeding was not induced by AAD-2004 even at a dose 400-fold higher than that required to obtain maximal therapeutic efficacy in SOD1G93A mice. Targeting both mPGES-1 and free radicals may be a promising approach to reduce neurodegeneration in ALS and possibly other neurodegenerative diseases

Ultrastrong and stress corrosion cracking-resistant martensitic steels

This study aims to reveal the atomic-scale effects of tempering on the complex substructures and stress corrosion cracking (SCC) resistance of high-strength martensitic steels. The SCC resistance and strength of boron-doped Fe-0.3C-0.3Si-1.0Mn-1.0Ni-0.5Cr (wt%) martensitic steel increase concurrently without low-temperature tempering. Notably, the degradation of SCC resistance caused by tempering is in con-trast with the known effect. To explore this unexpected result, subboundaries inside the martensitic mi-crostructure are investigated via atomic-nano-micro-scale analyses. The strongly segregated carbon at the lath boundaries during tempering is a precursor to the harmful cementite, which acts as severe SCC ini-tiation sites. Eventually, intensive crack grew along the lath boundaries, deteriorating the SCC resistance of the material. (c) 2022 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/

Timing dependent neuronal migration is regulated by Cdk5-mediated phosphorylation of JIP1

The mammalian brain, especially the cerebral cortex, has evolved to increase in size and complexity. The proper development of the cerebral cortex requires the coordination of several events, such as differentiation and migration, that are essential for forming a precise six-layered structure. We have previously reported that Cdk5-mediated phosphorylation of JIP1 at T205 modulates axonal out-growth. However, the spatiotemporal expression patterns and functions of these three genes (Cdk5, Cdk5r1 or p35, and Mapk8ip1 or JIP1) in distinct cell types during cortical development remain unclear. In this study, we analyzed single-cell RNA-sequencing data of mouse embryonic cortex and discovered that Cdk5, p35, and JIP1 are dynamically expressed in intermediate progenitors (IPs). Pseudotime analysis revealed that the expression of these three genes was concomitantly upregulated in IPs during neuronal migration and differentiation. By manipulating the expression of JIP1 and phospho-mimetic JIP1 using in utero electroporation, we showed that phosphorylated JIP1 at T205 affected the temporal migration of neurons

Serial CT Findings of Paragonimus Infested Dogs and the Micro-CT Findings of the Worm Cysts

OBJECTIVE: To investigate the serial CT findings of Paragonimus westermani infected dogs and the microscopic structures of the worm cysts using Micro-CT. MATERIALS AND METHODS: This study was approved by the committee on animal research at our institution. Fifteen dogs infected with P. westermani underwent serial contrast-enhanced CT scans at pre-infection, after 10 days of infection, and monthly thereafter until six months for determining the radiologic-pathologic correlation. Three dogs (one dog each time) were sacrificed at 1, 3 and 6 months, respectively. After fixation of the lungs, both multi-detector CT and Micro-CT were performed for examining the worm cysts. RESULTS: The initial findings were pleural effusion and/or subpleural ground-glass opacities or linear opacities at day 10. At day 30, subpleural and peribronchial nodules appeared with hydropneumothorax and abdominal or chest wall air bubbles. Cavitary change and bronchial dilatation began to be seen on CT scan at day 30 and this was mostly seen together with mediastinal lymphadenopathy at day 60. Thereafter, subpleural ground-glass opacities and nodules with or without cavitary changes were persistently observed until day 180. After cavitary change of the nodules, the migratory features of the subpleural or peribronchial nodules were seen on all the serial CT scans. Micro-CT showed that the cyst wall contained dilated interconnected tubular structures, which had communications with the cavity and the adjacent distal bronchus. CONCLUSION: The CT findings of paragonimiasis depend on the migratory stage of the worms. The worm cyst can have numerous interconnected tubular channels within its own wall and these channels have connections with the cavity and the adjacent distal bronchus

Meniscus-Guided Micro-Printing of Prussian Blue for Smart Electrochromic Display

Using energy-saving electrochromic (EC) displays in smart devices for augmented reality makes cost-effective, easily producible, and efficiently operable devices for specific applications possible. Prussian blue (PB) is a metal-organic coordinated compound with unique EC properties that limit EC display applications due to the difficulty in PB micro-patterning. This work presents a novel micro-printing strategy for PB patterns using localized crystallization of FeFe(CN)(6) on a substrate confined by the acidic-ferric-ferricyanide ink meniscus, followed by thermal reduction at 120 degrees C, thereby forming PB. Uniform PB patterns can be obtained by manipulating printing parameters, such as the concentration of FeCl3 center dot K3Fe(CN)(6), printing speed, and pipette inner diameter. Using a 0.1 M KCl (pH 4) electrolyte, the printed PB pattern is consistently and reversibly converted to Prussian white (CV potential range: -0.2-0.5 V) with 200 CV cycles. The PB-based EC display with a navigation function integrated into a smart contact lens is able to display directions to a destination to a user by receiving GPS coordinates in real time. This facile method for forming PB micro-patterns could be used for advanced EC displays and various functional devices

Complete Fracture of Sirolimus-Eluting Stent in a Saphenous Vein Graft to Left Anterior Descending Artery

Coronary stent fractures have been suggested as a potential new mechanism of restenosis. The mechanical properties of stents were designed not only to prevent vessel recoil, but also to resist the mechanical stress of vessel movement over millions of cardiac cycles. We present a case in which mechanical stress may have contributed to the fracture of a stent implanted in a saphenous vein graft (SVG) to the left coronary artery. The patient was admitted due to chest pain 2 years after receiving a coronary artery bypass graft. A coronary angiography revealed the culprit vessel to be the SVG to the left coronary artery. The graft was stenosed and was stented with a sirolimus-eluting stent. A 6-month follow-up coronary angiography revealed 80% in-stent restenosis with stent fracture. We re-intervened by balloon angioplasty. This is the first report of sirolimus-eluting stent fracture combined with restenosis of SVG in Korea

CT Findings of Atypical Adenomatous Hyperplasia in the Lung

OBJECTIVE: The aim of this study was to analyze the computed tomographic (CT) findings of atypical adenomatous hyperplasia (AAH) in the lung. MATERIALS AND METHODS: The CT findings of AAHs in eight patients were retrospectively reviewed. The CT findings of each AAH lesion were evaluated for multiplicity, location, shape, size and internal density of the lesion, the interface between the normal lung and the lesion, the internal features within the lesion and any change of the lesion on the follow-up CT scans (range: 33 to 540 days; average: 145.3 days). RESULTS: The eight patients consisted of three men and five women (age range: 43-71 years). Six of eight patients were asymptomatic. Four of them (50%) had synchronous malignancies in the lung: adenocarcinoma of the lung (n = 3), and metastatic squamous cell carcinoma from the uterus (n = 1). We could identify and evaluate eleven AAH nodules in seven patients on the CT scans. Three patients had multiple AAHs. Seven of the 11 lesions (64%) were located in the upper lobe. All the AAHs showed a well-defined oval or round shape and pure ground-glass opacity (GGO) without any solid component (size: 3.9x3 mm to 19x17 mm; internal attenuation: -467 to -785 HU). All the AAHs showed no change of their size and internal density on the follow-up CT scans. CONCLUSION: Atypical adenomatous hyperplasia is often associated with malignancy. This tumor is shown on CT as persistent well-defined oval or round nodular GGOs without solid components, and it does not change on the follow-up CT.This study is supported by KISTEP, Ministry of Science and Technology, Korea

Virtual surface morphology generation of Ti-6Al-4V directed energy deposition via conditional generative adversarial network

The core challenge in directed energy deposition is to obtain high surface quality through process optimisation, which directly affects the mechanical properties of fabricated parts. However, for expensive materials like Ti-6Al-4V, the cost and time required to optimise process parameters can be excessive in inducing good surface quality. To mitigate these challenges, we propose a novel method with artificial intelligence to generate virtual surface morphology of Ti-6Al-4V parts by given process parameters. A high-resolution surface morphology image generation system has been developed by optimising conditional generative adversarial networks. The developed virtual surface matches experimental cases well with an Frechet inception distance score of 174, in the range of accurate matching. Microstructural analysis with parts fabricated with artificial intelligence guidance exhibited less textured microstructural behaviour on the surface which reduces the anisotropy in the columnar structure. This artificial intelligence guidance of virtual surface morphology can help to obtain high-quality parts cost-effectively

Patterns of Recurrence after Breast-Conserving Treatment for Early Stage Breast Cancer by Molecular Subtype

Purpose: To study clinical features and patterns of recurrence after breast-conserving treatment (BCT) for three molecular subtypes of early stage breast cancer. Methods: The sample studied included 596 patients with T1-2N0-1 breast cancer who received BCT. Three groups were defined by receptor status. Luminal: estrogen receptor (ER) or progesterone receptor (PR) positive; triple negative (TN): ER, PR, and epidermal growth factor receptor-2 (HER2) receptor negative; and HER2 overexpressing: ER and PR negative but HER2 receptor positive. Results: The number of patients in each group was 408 (68.5%), 105 (17.6%), and 83 (13.9%), respectively. The median follow-up period was 79 months. The TN and HER2 subtypes occurred in younger patients (p=0.0007) and had higher nuclear grade and poorer histologic grade (p<0.0001 and 0.0071, respectively). During the follow-up period, locoregional recurrence was detected as th

Impact of Parenchymal Tuberculosis Sequelae on Mediastinal Lymph Node Staging in Patients with Lung Cancer

Because tuberculous (TB) involvement of mediastinal lymph nodes (LN) could cause false positive results in nodal staging of lung cancer, we examined the accuracy of nodal staging in lung cancer patients with radiographic sequelae of healed TB. A total of 54 lung cancer patients with radiographic TB sequelae in the lung parenchyma ipsilateral to the resected lung, who had undergone at least ipsilateral 4- and 7-lymph node dissection after both chest computed tomography (CT) and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT were included for the analysis. The median age of 54 subjects was 66 yr and 48 were males. Calcified nodules and fibrotic changes were the most common forms of healed parenchymal pulmonary TB. Enlarged mediastinal lymph nodes (short diameter > 1 cm) were identified in 21 patients and positive mediastinal lymph nodes were identified using FDG-PET/CT in 19 patients. The overall sensitivity and specificity for mediastinal node metastasis were 60.0% and 69.2% with CT and 46.7% and 69.2% with FDG-PET/CT, respectively. In conclusion, the accuracy of nodal staging using CT or FDG-PET/CT might be low in lung cancer patients with parenchymal TB sequelae, because of inactive TB lymph nodes without viable TB bacilli