Search Results (32)

Background/Objectives: Hutchinson–Gilford progeria syndrome (HGPS) is a rare genetic disorder that cause premature aging due to LMNA mutations and progerin accumulation. Although lonafarnib, an FDA-approved farnesyltransferase inhibitor, offers modest extension of life, the disease remains progressive. As progeria is associated with stem cell depletion and mesenchymal stem cell (MSC) therapy has shown efficacy in treating atherosclerosis, we aimed to evaluate its efficacy and safety in HGPS. Methods: A 7-year-old male with classic HGPS and preexisting severe cerebrovascular disease received four intravenous infusion of bone marrow-derived MSCs (2.5 × 10⁵ cells/kg) over 8 months. Growth, metabolic, cardiovascular, musculoskeletal, auditory, and inflammatory cytokines were monitored throughout the study. Prophylactic enoxaparin was administered to prevent vascular complications. Results: MSC therapy was associated with improved lean body mass (11.5%), bone mineral density (L-spine z-score: 0.55 → 2.03), reduced arterial stiffness (9.98% reductionin pulse wave velocity), joint range of motion, dentition, and decreased sICAM-1 levels. However, Cardiovascular deterioration continued, and the patient passed away 10 months after the fourth dose, likely due to progression of the underlying vascular disease. No severe adverse effects were attributed to MSC therapy. Conclusions: MSC therapy may offer short-term benefits in arterial stiffness, bone health and inflammation in HGPS without notable safety concerns. Further studies are warranted to validate these findings, explore earlier intervention, and determine long-term efficacy and optimal dosing strategies. Full article

Lung cancer, particularly non-small-cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality, with cisplatin-based chemotherapy being a standard treatment. However, the development of chemoresistance significantly limits its efficacy, necessitating alternative therapeutic approaches. Here, we demonstrate the anticancer effects of the extracts of Allium pseudojaponicum Makino (APE), a salt-tolerant plant, in cisplatin-resistant NSCLC. Metabolite profiling using UPLC-Q-TOF-MS^E identified 13 major compounds, predominantly alkaloids (71.65%) and flavonoids (8.81%), with key bioactive constituents such as lycorine (29.81%), tazettine (17.22%), and tricetin (8.19%). APE significantly inhibited cell viability in A549 and H460 cells, reducing viability to 38.6% (A549-Ctr), 37.2% (A549-CR), 28.4% (H460-Ctr), and 30.4% (H460-CR) at 40 µg/mL after 48 h. APE also suppressed colony formation by over 90% in both 2D and soft agar assays, while showing no cytotoxicity in normal human keratinocytes up to 80 µg/mL. Flow cytometry analysis revealed APE-induced G1 phase arrest, with the G1 population increasing from 50.4% to 56.6% (A549-Ctr) and 47.5% to 58.4% (A549-CR), accompanied by reduced S phase populations. This effect was associated with the downregulation of G1/S transition regulators, including cyclin D1, CDK4, cyclin E, and CDK2. Furthermore, proteomic analysis identified STAT3 signaling as a major target of APE; APE decreased phosphorylated STAT3 and c-Myc expression, and STAT3 knockdown phenocopied the effects of APE. These findings highlight the potential of APE as a natural product-based therapeutic strategy for overcoming cisplatin resistance in NSCLC. Full article

As malware continues to evolve, AI-based malware classification methods have shown significant promise in improving the malware classification performance. However, these methods lead to a substantial increase in computational complexity and the number of parameters, increasing the computational cost during the training process. Moreover, the maintenance cost of these methods also increases, as frequent retraining and transfer learning are required to keep pace with evolving malware variants. In this paper, we propose an efficient knowledge distillation technique for AI-based malware classification methods called Self-MCKD. Self-MCKD transfers output logits that are separated into the target class and non-target classes. With the separation of the output logits, Self-MCKD enables efficient knowledge transfer by assigning weighted importance to the target class and non-target classes. Also, Self-MCKD utilizes small and shallow AI-based malware classification methods as both the teacher and student models to overcome the need to use large and deep methods as the teacher model. From the experimental results using various malware datasets, we show that Self-MCKD outperforms the traditional knowledge distillation techniques in terms of the effectiveness and efficiency of its malware classification. Full article

Root extracts of Ancistrocladus tectorius (AT), a shrub native to China, have been shown to have antiviral and antitumor activities, but the anti-obesity effects of AT aerial parts, mainly the leaves and stems, have not been investigated. This study is the first to investigate the anti-obesity effects and molecular mechanism of AT 70% ethanol extract in 3T3-L1 adipocytes and high-fat diet (HFD)-fed C57BL/6J mice. Treatment with AT extract inhibited lipid accumulation in 3T3-L1 cells and decreased the expression of adipogenesis-related genes. AT extract also upregulated the mRNA expression of genes related to mitochondrial dynamics in 3T3-L1 adipocytes. AT administration for 12 weeks reduced body weight and organ weights, including liver, pancreas, and white and brown adipose tissue, and improved plasma profiles such as glucose, insulin, homeostasis model assessment of insulin resistance, triglyceride (TG), and total cholesterol in HFD-fed mice. AT extract reduced HFD-induced hepatic steatosis with levels of liver TG and lipogenesis-related genes. AT extract upregulated thermogenesis-related genes such as Cidea, Pgc1α, Ucp1, Prdm16, Adrb1, and Adrb3 and mitochondrial dynamics-related genes such as Mff, Opa1, and Mfn2 in brown adipose tissue (BAT). Therefore, AT extract effectively reduced obesity by promoting thermogenesis and the mitochondrial dynamics of BAT in HFD-fed mice. Full article

Globally, renewable energies are indispensable resources on account of RE100 and the Paris Agreement. The most developed renewable energies are photovoltaics (PV) and wind energy, and they are continuously expanding. This study aims to optimize and analyze the nuclear power plant (NPP) load-following operation in various PV conditions in a metropolitan region. With theoretically estimated power demand and PV power, a mixed-integer problem (MIP) with ramping cycle constraint (RCC) was constructed for a safe load-following operation and simulated through duck curves under various NPP load-following regions (the extreme, normal, and safe regions). The simulation showed two major results for NPP load-following. Technically, RCC successfully controlled the NPP ramp cycle and was assured to be an optimization tool for NPP operation. Numerically, NPP load-following alleviated PV intermittency to almost 50%, 30%, and 15% depending on the load-following region. However, these effects were restricted when the PV capacity rate was high, especially when it exceeded 60%. Thus, PV system capacity is recommended to be 63% of the maximum power demand in the metropolitan region with NPP load-following, and larger PV systems need more flexibility. Full article

This study aims to evaluate the effect of chitosan coating on the formation and properties of Bacillus cyclic lipopeptide (CLP)-loaded liposomes. A nanoencapsulation strategy for a chitosan-coated liposomal system using lecithin phospholipids for the entrapment of antibiotic CLP prepared from Bacillus subtilis KB21 was developed. The produced chitosan-coated CLP liposome had mean size in the range of 118.47–121.67 nm. Transmission electron microscopy showed the spherical-shaped vesicles. Fourier transform infrared spectroscopy findings indicated the successful coating of the produced CLP-loaded liposomes by the used chitosan. Liposomes coated with 0.2% and 0.5% chitosan concentration decreased the surface tension by 7.3–12.1%, respectively, and increased the CLP content by 15.1–27.0%, respectively, compared to the uncoating liposomes. The coated concentration of chitosan influenced their CLP loading encapsulation efficiency and release kinetics. The physicochemical results of the dynamic light scattering, CLP capture efficiency and long-term storage capacity of nanocapsules increased with chitosan coating concentration. Furthermore, the chitosan-coated liposomes exhibited a significant enhancement in the stability of CLP loading liposomes. These results may suggest the potential application of chitosan-coated liposomes as a carrier of antibiotics in the development of the functional platform. Full article

Utilizing pre-trained models involves fully or partially using pre-trained parameters as initialization. In general, configuring a pre-trained model demands practitioners’ knowledge about problems or an exhaustive trial–error experiment according to a given task. In this paper, we propose tuning trainable layers using a genetic algorithm on a pre-trained model that is fine-tuned on single-channel image datasets for a classification task. The single-channel dataset comprises images from grayscale and preprocessed audio signals transformed into a log-Mel spectrogram. Four deep-learning models used in the experimental evaluation employed the pre-trained model with the ImageNet dataset. The proposed genetic algorithm was applied to find the highest fitness for every generation to determine the selective layer tuning of the pre-trained models. Compared to the conventional fine-tuning method and random layer search, our proposed selective layer search with a genetic algorithm achieves higher accuracy, on average, by 9.7% and 1.88% (MNIST-Fashion), 1.31% and 1.14% (UrbanSound8k), and 2.2% and 0.29% (HospitalAlarmSound), respectively. In addition, our searching method can naturally be applied to various datasets of the same task without prior knowledge about the dataset of interest. Full article

Nanoparticles have garnered significant interest in neurological research in recent years owing to their efficient penetration of the blood–brain barrier (BBB). However, significant concerns are associated with their harmful effects, including those related to the immune response mediated by microglia, the resident immune cells in the brain, which are exposed to nanoparticles. We analysed the cytotoxic effects of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO₂(RITC)] in a BV2 microglial cell line using systems toxicological analysis. We performed the invasion assay and the exocytosis assay and transcriptomics, proteomics, metabolomics, and integrated triple-omics analysis, generating a single network using a machine learning algorithm. The results highlight alteration in the mechanisms of the nanotoxic effects of nanoparticles using integrated omics analysis. Full article

Acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus (Vp_AHPND) has been reported in commodity shrimp, but the potential risk of its global spread via frozen shrimp in the shrimp trade is yet to be fully explored. We hypothesized that frozen shrimp with AHPND could be a source of Vp_AHPND transmission; thus, the infectivity of frozen shrimp with AHPND was evaluated using a shrimp bioassay. To prepare infected frozen shrimp, 12 Penaeus vannamei (average weight, 2 g) were exposed to Vp_AHPND by immersion in water with a Vp_AHPND concentration of 1.55 × 10⁷ CFU mL⁻¹; once dead, the shrimp were stored at −80 °C for further analysis. After two weeks, a PCR assay was used to confirm AHPND positivity in frozen shrimp (n = 2), and Vp_AHPND was reisolated from the hepatopancreases of these shrimp. For the infectivity test, 10 P. vannamei (average weight, 4 g) were fed with the hepatopancreases of Vp_AHPND -infected frozen shrimp (n = 10). After feeding, 70% of the shrimp died within 118 h, and the presence of Vp_AHPND was confirmed using a PCR assay and histopathology examination; moreover, Vp_AHPND was successfully reisolated from the hepatopancreases of the dead shrimp. We are the first to evaluate the potential transmissibility of Vp_AHPND in frozen shrimp, and our results suggest that frozen shrimp with AHPND are a potential source of disease spreading between countries during international trade. Full article

Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early discrimination of macrolide-refractory M. pneumoniae pneumonia (MrMP) from macrolide-sensitive M. pneumoniae pneumonia (MSMP) is vital; however, testing for macrolide susceptibility at the time of admission is not feasible. This study aimed to identify the characteristics of MrMP in Korean children, in comparison with those of MSMP. In this multicenter study, board-certified pediatric pulmonologists at 22 tertiary hospitals reviewed the medical records from 2010 to 2015 of 5294 children who were hospitalized with M. pneumoniae pneumonia and administered macrolides as the initial treatment. One-way analysis of variance and the Kruskal-Wallis test were used to compare differences between groups. Of 5294 patients (mean age, 5.6 years) included in this analysis, 240 (4.5%), 925 (17.5%), and 4129 (78.0%) had MrMP, macrolide-less effective M. pneumoniae pneumonia, and MSMP, respectively. Compared with the MSMP group, the MrMP group had a longer fever duration, overall (13.0 days) and after macrolide use (8.0 days). A higher proportion of MrMP patients had respiratory distress, pleural effusion, and lobar pneumonia. The mean aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein levels were the highest in the MrMP group, along with higher incidences of extrapulmonary manifestations and atelectasis (during and post infection). Pre-existing conditions were present in 17.4% (n = 725/4159) of patients, with asthma being the most common (n = 334/4811, 6.9%). This study verified that MrMP patients show more severe initial radiographic findings and clinical courses than MSMP patients. MrMP should be promptly managed by agents other than macrolides. Full article

A number of studies have utilized blood waste as a bioresource by enzymatic hydrolysis to obtain amino acids, such as branched-chain amino acids, which can increase muscle mass or prevent muscle loss during weight loss. Although a significantly high content of branched-chain amino acids has been reported in porcine whole-blood protein hydrolysate (PWBPH), the effects of PWBPH on skeletal muscle differentiation and exercise function remain unclear. In this study, we investigated the effects of PWBPH on exercise endurance in ICR mice and muscle differentiation in C2C12 mouse myoblasts and gastrocnemius (Gas) muscle of mice. Supplementation with PWBPH (250 and 500 mg/kg for 5 weeks) increased the time to exhaustion on a treadmill. PWBPH also increased the Gas muscle weight to body weight ratio. In addition, PWBPH treatment increased skeletal muscle differentiation proteins and promoted the Akt/mTOR-dependent signaling pathway in vitro and in vivo. These results suggest that PWBPH can be utilized as a bioresource to enhance exercise function and skeletal muscle differentiation. Full article

Epstein–Barr-virus-associated gastric carcinoma (EBVaGC), first reported in 1992, currently accounts for 10% of all gastric carcinoma worldwide. EBVaGC has unique DNA hypermethylation phenotypes that allow for higher proportions of DNA methylation than any other gastric cancer. CpG islands in the gene promoter region are one of the major regions in which DNA methylation controls gene transcription. Despite cisplatin-based chemotherapy being one of the standard treatment regimens for advanced gastric cancer, including EBVaGC, cisplatin alone or in combination with 5-fluorouracil has been limited by its less potent anticancer activity and the occurrence of cisplatin resistance. Accordingly, the current study evaluated the anticancer activities of a combination of cisplatin and 5-Azacytidine (5-AZA) against EBVaGC. Our findings showed that cisplatin upregulated the DNMT3A gene, whereas shRNA-targeted removal of DNMT3A mRNA contributed to cisplatin-mediated EBV lytic reactivation. Moreover, the removal of DNMT3A mRNA upregulated the ATM gene through DNA demethylation on the ATM promoter. Furthermore, CRISPR/Cas9-targeted removal of the ATM gene resulted in significantly reduced cell susceptibility and EBV lytic reactivation by a combination of cisplatin and DNMT3A inhibitor 5-AZA. Finally, 5-AZA exhibited a synergistic effect with cisplatin in anti-EBV and anti-EBVaGC activities by increasing drug susceptibility and EBV lytic reactivation. The aforementioned results suggest that cisplatin combined with DNA methylation inhibitors could be a novel therapeutic approach for EBVaGC. Full article

A number of research attempts to understand and modulate sensory and motor skills that are beyond the capability of humans have been underway. They have mainly been expounded in rodent models, where numerous reports of controlling movement to reach target locations by brain stimulation have been achieved. However, in the case of birds, although basic research on movement control has been conducted, the brain nuclei that are triggering these movements have yet to be established. In order to fully control flight navigation in birds, the basic central nervous system involved in flight behavior should be understood comprehensively, and functional maps of the birds’ brains to study the possibility of flight control need to be clarified. Here, we established a stable stereotactic surgery to implant multi-wire electrode arrays and electrically stimulated several nuclei of the pigeon’s brain. A multi-channel electrode array and a wireless stimulation system were implanted in thirteen pigeons. The pigeons’ flight trajectories on electrical stimulation of the cerebral nuclei were monitored and analyzed by a 3D motion tracking program to evaluate the behavioral change, and the exact stimulation site in the brain was confirmed by the postmortem histological examination. Among them, five pigeons were able to induce right and left body turns by stimulating the nuclei of the tractus occipito-mesencephalicus (OM), nucleus taeniae (TN), or nucleus rotundus (RT); the nuclei of tractus septo-mesencephalicus (TSM) or archistriatum ventrale (AV) were stimulated to induce flight aviation for flapping and take-off with five pigeons. Full article

For an engineering feasibility study, we studied a simple design to improve NCSS (nanocarbon composite strain sensor) sensitivity by using its geometric pattern at a macro scale. We fabricated bulk- and grid-type sensors with different filler content weights (wt.%) and different sensor lengths and investigated their sensitivity characteristics. We also proposed a unit gauge factor model of NCSS to find a correlation between sensor length and its sensitivity. NCSS sensitivity was improved proportional to its length incremental ratio and we were able to achieve better linear and consistent data from the grid type than the bulk type one. We conclude that the longer sensor length results in a larger change of resistance due to its piezoresistive unit summation and that sensor geometric pattern design is one of the important issues for axial load and deformation measurement. Full article

We reviewed the clinical characteristics and treatment outcomes of patients with glomus tympanicum tumors (GTTs) presenting with pulsatile tinnitus (PT). We explored whether transcanal sound recording-spectro-temporal analysis (TSR-STA) usefully evaluated changes in PT. The medical records of 13 patients who underwent surgical removal of GTTs were reviewed retrospectively. Two patients underwent preoperative endovascular embolization. Changes in PT, pre- and postoperative audiometry data, TSR-STA results, and clinical outcomes were evaluated. PT was the chief complaint in eight patients (61.5%) and resolved immediately after surgical intervention in all. Two patients exhibited ipsilateral, pseudo-low-frequency hearing loss (PLFHL); surgical GTT removal elicited postoperative improvements in the ipsilesional low-frequency hearing thresholds. Five patients underwent TSR-STA using previously described methods. TSR-STA revealed definite rise-and-fall patterns; surgical tumor removal abated this pattern in one patient, but, for the other four, the patterns did not change greatly post-intervention. Thus, GTT-related PT can be treated successfully (via surgical GTT removal) without complications. In selected cases, preoperative embolization reduces intraoperative hemorrhage. In PT patients with PLFHL, a detailed otoendoscopic examination of the middle ear is required to rule out a GTT. TSR-STA may usefully (and objectively) assess postoperative improvements in GTT-related PT. Full article