Regenerative capacity of alveolar type 2 cells is proportionally reduced following disease progression in idiopathic pulmonary fibrosis-derived organoid cultures.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that leads to respiratory failure and death due to irreversible scarring of the distal lung. While historically considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now recognized to play a central role in IPF pathophysiology. PURPOSE: This study aimed to investigate the regenerative capacity of AT2 cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. METHOD: Lung tissues from 3 pneumothorax patients and 6 IPF patients (early and advanced stages) were obtained by VATS and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-EpCAM+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immuno-staining was used to confirm the presence of AT2 cells. RESULTS: FACS sorting yielded approximately 1% AT2 cells of the total cells in early IPF tissue, and the number decreased as the disease progressed, compared with 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller in size and fewer in number compared to those from pneumothorax patients. The colony-forming efficiency decreased as the disease progressed. In immuno-staining results, the IPF organoids showed lower expression of SFTPC compared to the pneumothorax group and contained KRT5+ cells. CONCLUSION: This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, and IPF AT2 cells inherently exhibit functional abnormalities and altered differentiation plasticity.

Lithium-silver alloys in anode-less batteries: comparison in liquid- and solid-electrolytes.

This study comprehensively investigates the phase evolution of silver-carbon composite (Ag/C) layers in anode-less batteries with both liquid and solid electrolytes. The results of in situ X-ray diffraction and cross-sectional electron microscopy analyses reveal that the alloying reaction of Ag and Li is more homogeneous in solid-electrolyte-based cells compared to liquid-electrolyte-based cells. This homogeneity is attributed to diffusional Coble creep across the heterogeneous interfaces of Ag/C layers and solid electrolytes.

Artificial Intelligence-Based Anomaly Detection Technology over Encrypted Traffic: A Systematic Literature Review.

As cyber-attacks increase in unencrypted communication environments such as the traditional Internet, protected communication channels based on cryptographic protocols, such as transport layer security (TLS), have been introduced to the Internet. Accordingly, attackers have been carrying out cyber-attacks by hiding themselves in protected communication channels. However, the nature of channels protected by cryptographic protocols makes it difficult to distinguish between normal and malicious network traffic behaviors. This means that traditional anomaly detection models with features from packets extracted a deep packet inspection (DPI) have been neutralized. Recently, studies on anomaly detection using artificial intelligence (AI) and statistical characteristics of traffic have been proposed as an alternative. In this review, we provide a systematic review for AI-based anomaly detection techniques over encrypted traffic. We set several research questions on the review topic and collected research according to eligibility criteria. Through the screening process and quality assessment, 30 research articles were selected with high suitability to be included in the review from the collected literature. We reviewed the selected research in terms of dataset, feature extraction, feature selection, preprocessing, anomaly detection algorithm, and performance indicators. As a result of the literature review, it was confirmed that various techniques used for AI-based anomaly detection over encrypted traffic were used. Some techniques are similar to those used for AI-based anomaly detection over unencrypted traffic, but some technologies are different from those used for unencrypted traffic.

Effect of the Interaction between Transition Metal Redox Center and Cyanide Ligand on Structural Evolution in Prussian White Cathodes.

Transition metal (TM) based Prussian whites, comprising a cyanide anion ((C≡N)-) and TM cations in an alternative manner, have been widely adopted as cathode materials for rechargeable batteries. Prussian whites are characterized by the TM electronic states that exclusively adopt low spin (LS) toward the C atom and high spin (HS) toward the N atom through the hybridized covalent bonding in the TM─C≡N─TM unit with the average oxidation states of the TM ions being 2+, considerably affecting the phase transition behavior upon the release and storage of carrier ions; however, there have been only a few studies on their associated features. Herein, Prussian whites with different HS TM ions were synthesized via coprecipitation and the phase transition behavior controlled by the π electron interaction between the cyanide anions and TM ions during battery operations was investigated. In situ X-ray characterizations reveal that the combined effect of π backdonation in the LS Fe-C unit and π donation in the HS TM-N unit effectively controls the bond length of the TM─C≡N─TM building unit, thus markedly influencing the lattice volume of a series of Prussian white cathodes during the charge/discharge process. This study presents a comprehensive understanding of the structure-property relationship of the Prussian white cathodes involving π electron interactions during battery operations.

Generating ICS Anomaly Data Reflecting Cyber-Attack Based on Systematic Sampling and Linear Regression.

Cyber threats to industrial control systems (ICSs) have increased as information and communications technology (ICT) has been incorporated. In response to these cyber threats, we are implementing a range of security equipment and specialized training programs. Anomaly data stemming from cyber-attacks are crucial for effectively testing security equipment and conducting cyber training exercises. However, securing anomaly data in an ICS environment requires a lot of effort. For this reason, we propose a method for generating anomaly data that reflects cyber-attack characteristics. This method uses systematic sampling and linear regression models in an ICS environment to generate anomaly data reflecting cyber-attack characteristics based on benign data. The method uses statistical analysis to identify features indicative of cyber-attack characteristics and alters their values from benign data through systematic sampling. The transformed data are then used to train a linear regression model. The linear regression model can predict features because it has learned the linear relationships between data features. This experiment used ICS_PCAPS data generated based on Modbus, frequently used in ICS. In this experiment, more than 50,000 new anomaly data pieces were generated. As a result of using some of the new anomaly data generated as training data for the existing model, no significant performance degradation occurred. Additionally, comparing some of the new anomaly data with the original benign and attack data using kernel density estimation confirmed that the new anomaly data pattern was changing from benign data to attack data. In this way, anomaly data that partially reflect the pattern of the attack data were created. The proposed method generates anomaly data like cyber-attack data quickly and logically, free from the constraints of cost, time, and original cyber-attack data required in existing research.

InZnTiON Channel Layer for Highly Stable Thin-Film Transistors and Light-Emitting Transistors.

In this study, we incorporated TiN as a carrier suppressor into an amorphous InZnO channel to achieve stable channels for thin-film transistors (TFTs) and light-emitting transistors (LETs). The low electronegativity and standard electrode potential of the Ti dopant led to a reduction in the number of oxygen vacancies in the InZnO channel. Moreover, the substitution of nitrogen into the oxygen sites of InZnO effectively decreased the excess electrons. As a result, the cosputtering of the TiN dopant resulted in a decrease in the carrier concentration of the InZnO channel, serving as an effective carrier suppressor. Due to the distinct structures of TiN and InZnO, the TiN-doped InZnO channel exhibited a completely amorphous structure and a featureless surface morphology. The presence of oxygen vacancies in the InZnO channel creates trap states for electrons and holes. Consequently, the TFT with the InZnTiON channel demonstrated an improved subthreshold swing and enhanced stability during the gate bias stress test. Furthermore, the threshold voltage shift (ΔVth) changed from 3.29 to 0.86 V in the positive bias stress test and from -0.92 to -0.09 V in the negative bias stress test. Additionally, we employed an InZnTiON channel in LETs as a substitute for organic semiconductors. The reduction in the number of oxygen vacancies effectively prevented exciton quenching caused by hole traps within the vacancies. Consequently, appropriate TiN doping in the InZnO channel enhanced the intensity of the LET devices.

Maternal Embryonic Leucine Zipper Kinase is Associated with Metastasis in Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) has high relapse and metastasis rates and a high proportion of cancer stem-like cells (CSC), which possess self-renewal and tumor initiation capacity. MELK (maternal embryonic leucine zipper kinase), a protein kinase of the Snf1/AMPK kinase family, is known to promote CSC maintenance and malignant transformation. However, the role of MELK in TNBC metastasis is unknown; we sought to address this in the current study. We found that MELK mRNA levels were higher in TNBC tumors [8.11 (3.79-10.95)] than in HR+HER2- tumors [6.54 (2.90-9.26)]; P < 0.001]. In univariate analysis, patients with breast cancer with high-MELK-expressing tumors had worse overall survival (P < 0.001) and distant metastasis-free survival (P < 0.01) than patients with low-MELK-expressing tumors. In a multicovariate Cox regression model, high MELK expression was associated with shorter overall survival after adjusting for other baseline risk factors. MELK knockdown using siRNA or MELK inhibition using the MELK inhibitor MELK-In-17 significantly reduced invasiveness, reversed epithelial-to-mesenchymal transition, and reduced CSC self-renewal and maintenance in TNBC cells. Nude mice injected with CRISPR MELK-knockout MDA-MB-231 cells exhibited suppression of lung metastasis and improved overall survival compared with mice injected with control cells (P < 0.05). Furthermore, MELK-In-17 suppressed 4T1 tumor growth in syngeneic BALB/c mice (P < 0.001). Our findings indicate that MELK supports metastasis by promoting epithelial-to-mesenchymal transition and the CSC phenotype in TNBC. Significance: These findings indicate that MELK is a driver of aggressiveness and metastasis in TNBC.

Overcoming the imatinib-resistant BCR-ABL mutants with new ureidobenzothiazole chemotypes endowed with potent and broad-spectrum anticancer activity.

The design of kinase inhibitors targeting the oncogenic kinase BCR-ABL constitutes a promising paradigm for treating chronic myeloid leukaemia (CML). Nevertheless, the efficacy of imatinib, the first FDA-approved targeted therapy for CML, is curbed by the emergence of resistance. Herein, we report the identification of the 2-methoxyphenyl ureidobenzothiazole AK-HW-90 (2b) as a potent pan-BCR-ABL inhibitor against imatinib-resistant mutants, particularly T315I. A concise array of six compounds 2a-f was designed based on our previously reported benzothiazole lead AKE-5l to improve its BCR-ABLT315I inhibitory activity. Replacing the 6-oxypicolinamide moiety of AKE-5l with o-methoxyphenyl and changing the propyl spacer with phenyl afforded 2a and AK-HW-90 (2b) with IC50 values of 2.0 and 0.65 nM against BCR-ABLT315I, respectively. AK-HW-90 showed superior anticancer potency to imatinib against multiple cancer cells (NCI), including leukaemia K-562. The obtained outcomes offer AK-HW-90 as a promising candidate for the treatment of CML and other types of cancer.

Structural Evolution of Mg-Doped Single-Crystal LiCoO2 Cathodes: Importance of Morphology and Mg-Doping Sites.

Layered lithium cobalt oxide (LiCoO2, LCO), which serves as a structural motif for the widely adopted layered cathodes in lithium-ion batteries, has a long history, and its unstable phase transition during high-voltage operation (∼4.5 V) remains an intractable problem. Many research strategies, such as surface coating and immobile ion doping, have been proposed to address this issue, but a clear understanding of the effects has not been demonstrated because of various potential parameters (e.g., particle size, shape, and dopant content). Herein, we report a molten salt synthesis method that produces sphere-like single-crystal magnesium (Mg)-doped LCO. In situ X-ray diffraction and X-ray absorption fine structure analyses confirmed that the lattice strain was effectively alleviated by the effects of both the particle shape and Mg doping compared to the plate-like and sphere-like single-crystal LCO samples. Furthermore, the preference for Mg doping in the Co site (3b) rather than in the Li site (3a) in the LCO framework is systematically revealed, and a clear understanding of Mg doping that suppresses the monoclinic phase transition is discussed in detail.