Understanding NK cell biology for harnessing NK cell therapies: targeting cancer and beyond

Gene-engineered immune cell therapies have partially transformed cancer treatment, as exemplified by the use of chimeric antigen receptor (CAR)-T cells in certain hematologic malignancies. However, there are several limitations that need to be addressed to target more cancer types. Natural killer (NK) cells are a type of innate immune cells that represent a unique biology in cancer immune surveillance. In particular, NK cells obtained from heathy donors can serve as a source for genetically engineered immune cell therapies. Therefore, NK-based therapies, including NK cells, CAR-NK cells, and antibodies that induce antibody-dependent cellular cytotoxicity of NK cells, have emerged. With recent advances in genetic engineering and cell biology techniques, NK cell-based therapies have become promising approaches for a wide range of cancers, viral infections, and senescence. This review provides a brief overview of NK cell characteristics and summarizes diseases that could benefit from NK-based therapies. In addition, we discuss recent preclinical and clinical investigations on the use of adoptive NK cell transfer and agents that can modulate NK cell activity

MicroRNA-150 modulates intracellular Ca2+ levels in naïve CD8+ T cells by targeting TMEM20

Regulation of intracellular Ca2+ signaling is a major determinant of CD8+ T cell responsiveness, but the mechanisms underlying this regulation of Ca2+ levels, especially in naïve CD8+ T cells, are not fully defined. Here, we showed that microRNA-150 (miR-150) controls intracellular Ca2+ levels in naïve CD8+ T cells required for activation by suppressing TMEM20, a negative regulator of Ca2+ extrusion. miR-150 deficiency increased TMEM20 expression, which resulted in increased intracellular Ca2+ levels in naïve CD8+ T cells. The subsequent increase in Ca2+ levels induced expression of anergy-inducing genes, such as Cbl-b, Egr2, and p27, through activation of NFAT1, as well as reduced cell proliferation, cytokine production, and the antitumor activity of CD8+ T cells upon antigenic stimulation. The anergy-promoting molecular milieu and function induced by miR-150 deficiency were rescued by reinstatement of miR-150. Additionally, knockdown of TMEM20 in miR-150-deficient naïve CD8+ T cells reduced intracellular Ca2+ levels. Our findings revealed that miR-150 play essential roles in controlling intracellular Ca2+ level and activation in naïve CD8+ T cells, which suggest a mechanism to overcome anergy induction by the regulation of intracellular Ca2+ levels115Ysciescopu

A New Circuit Design of AC/DC Converter for T8 LED Tube

This study is about an improved high-quality light-emitting diode (LED) converter for a T8 LED tube. The converter is separated into the AC driving circuit and DC driving circuit. Also, the LED tube was applied with an output ripple eliminator for the optical performance. The AC driving circuit and DC driving circuit are assembled at the end of the LED tube in a G13 base and a G13 base dummy, respectively, and the output ripple eliminator is located on an LED PCB. The proposed LED converter is founded on a SSBB (single-stage buck-boost) converter topology and was designed for 10 W operation for a 600 mm T8 LED tube. The light waveform of the LED tube was measured by a photosensor. The waveform had almost no ripple and was the same as a straight line. The average calculated percent flicker of the proposed LED converter was an average of 1.9% at 100 and 240 VAC, 50 and 60 Hz. The proposed converter has lower power efficiency than a conventional converter by 2.7% at 100–240 VAC, but it still has high power efficiency (>87%). The measurement results represent that the LED output current regulation is below 0.92% at 100–240 VAC and the converter obtains the power factor more than 0.84 and the total harmonic distortion is less than 14.3%. All of the current harmonics reach the IEC 61000-3-2 Class D standards for high-quality LED converters

Ensemble Prediction Model for Dust Collection Efficiency of Wet Electrostatic Precipitator

WESPs (Wet Electrostatic precipitators) are mainly installed in industries and factories where PM (particulate matter) is primarily generated. Such a wet type WESPs exhibits very excellent performance by showing a PM collection efficiency of 97 to 99%, but the PM collection efficiency may decrease rapidly due to a situation in which the dust collector and the discharge electrode is corroded by water. Thus, developing technology to predict efficient PM collection in the design and operation of WESPs is critical. Previous studies have mainly developed machine learning-based models to predict atmospheric PM concentrations using data measured by meteorological agencies. However, the analysis of models for predicting the dust collection efficiency of WESPs installed in factories and industrial facilities is insufficient. In this study, a WESPs was installed, and PM collection experiments were conducted. Nonlinear data such as operating conditions and PM measurements were collected, and ensemble PM collection efficiency prediction models were developed. According to the research results, the random forest model yielded excellent performance, with the best results achieved when the target was PM 7: R2, MAE, and MSE scores of 0.956, 0.747, and 1.748, respectively

Rotor Fault Diagnosis Method Using CNN-Based Transfer Learning with 2D Sound Spectrogram Analysis

This study discusses a failure detection algorithm that uses frequency analysis and artificial intelligence to determine whether a rotor used in an industrial setting has failed. A rotor is a standard component widely used in industrial sites, and continuous friction and corrosion frequently result in motor and bearing failures. As workers inspecting failure directly are at risk of serious accidents, an automated environment that can operate unmanned and a system for accurate failure determination are required. This study proposes an algorithm to detect faults by introducing convolutional neural networks (CNNs) after converting the fault sound from the rotor into a spectrogram through STFT analysis and visually processing it. A binary classifier for distinguishing between normal and failure states was added to the output part of the neural network structure used, which was based on the transfer learning methodology. We mounted the proposed structure on a designed embedded system to conduct performance discrimination experiments and analyze various outcome indicators using real-world fault data from various situations. The analysis revealed that failure could be detected in response to various normal and fault sounds of the field system and that both training and validation accuracy were greater than 99%. We further intend to investigate artificial intelligence algorithms that train and learn by classifying fault types into early, middle, and late stages to identify more specific faults

Emerging Approaches for Solid Tumor Treatment Using CAR-T Cell Therapy

Cancer immunotherapy is becoming more important in the clinical setting, especially for cancers resistant to conventional chemotherapy, including targeted therapy. Chimeric antigen receptor (CAR)-T cell therapy, which uses patient’s autologous T cells, combined with engineered T cell receptors, has shown remarkable results, with five US Food and Drug Administration (FDA) approvals to date. CAR-T cells have been very effective in hematologic malignancies, such as diffuse large B cell lymphoma (DLBCL), B cell acute lymphoblastic leukemia (B-ALL), and multiple myeloma (MM); however, its effectiveness in treating solid tumors has not been evaluated clearly. Therefore, many studies and clinical investigations are emerging to improve the CAR-T cell efficacy in solid tumors. The novel therapeutic approaches include modifying CARs in multiple ways or developing a combination therapy with immune checkpoint inhibitors and chemotherapies. In this review, we focus on the challenges and recent advancements in CAR-T cell therapy for solid tumors

Causes and Mechanisms of Hematopoietic Stem Cell Aging

Many elderly people suffer from hematological diseases known to be highly age-dependent. Hematopoietic stem cells (HSCs) maintain the immune system by producing all blood cells throughout the lifetime of an organism. Recent reports have suggested that HSCs are susceptible to age-related stress and gradually lose their self-renewal and regeneration capacity with aging. HSC aging is driven by cell-intrinsic and -extrinsic factors that result in the disruption of the immune system. Thus, the study of HSC aging is important to our understanding of age-related immune diseases and can also provide potential strategies to improve quality of life in the elderly. In this review, we delineate our understanding of the phenotypes, causes, and molecular mechanisms involved in HSC aging

Pharmacological Regulation of Oxidative Stress in Stem Cells

Oxidative stress results from an imbalance between reactive oxygen species (ROS) production and antioxidant defense mechanisms. The regulation of stem cell self-renewal and differentiation is crucial for early development and tissue homeostasis. Recent reports have suggested that the balance between self-renewal and differentiation is regulated by the cellular oxidation-reduction (redox) state; therefore, the study of ROS regulation in regenerative medicine has emerged to develop protocols for regulating appropriate stem cell differentiation and maintenance for clinical applications. In this review, we introduce the defined roles of oxidative stress in pluripotent stem cells (PSCs) and hematopoietic stem cells (HSCs) and discuss the potential applications of pharmacological approaches for regulating oxidative stress in regenerative medicine

Dysregulation of Rho GTPases in Human Cancers

Rho GTPases play central roles in numerous cellular processes, including cell motility, cell polarity, and cell cycle progression, by regulating actin cytoskeletal dynamics and cell adhesion. Dysregulation of Rho GTPase signaling is observed in a broad range of human cancers, and is associated with cancer development and malignant phenotypes, including metastasis and chemoresistance. Rho GTPase activity is precisely controlled by guanine nucleotide exchange factors, GTPase-activating proteins, and guanine nucleotide dissociation inhibitors. Recent evidence demonstrates that it is also regulated by post-translational modifications, such as phosphorylation, ubiquitination, and sumoylation. Here, we review the current knowledge on the role of Rho GTPases, and the precise mechanisms controlling their activity in the regulation of cancer progression. In addition, we discuss targeting strategies for the development of new drugs to improve cancer therapy