Enhanced anti-cancer effect using MMP-responsive L-asparaginase fused with cell-penetrating 30Kc19 protein

As the acute lymphoblastic leukaemia (ALL) develops, expression of L-asparaginase (ASNase) protein is known to decrease. Therefore, deficiency of the ASNase protein would be regarded as one of the significant indications of the ALL. For the treatment of ALL, recombinant ASNase protein derived from bacterial origin is used which causes cytotoxicity by deprivation of Asn. However, short half-life of the protein is an obstacle for medical use. In order to overcome this limit, recombinant ASNase was fused to 30Kc19 with protein-stabilizing and cell-penetrating properties. As the 30Kc19 protein may induce steric hindrance, we further added a PLGLAG linker sequence (LK) between the ASNase and 30Kc19. The treatment of ASNase-LK-30Kc19 fusion protein demonstrated enhanced stability, cell-penetrating property, and anti-cancer activity. Intracellular delivery of both the non-cleaved and cleaved forms of the protein were observed, suggesting that ASNase acted both internally and externally, performing high anti-cancer activity by effective depletion of intracellular Asn. Additionally, ASNase-LK-30Kc19 showed high selectivity towards cancer cells. In terms of the dosage, releasable ASNase from ASNase-LK-30Kc19 reached the same half-maximal inhibitory concentration at a concentration five times lower than non-releasable ASNase-30Kc19. Altogether, the findings suggest that this fusion approach has potential applications in the treatment of ALL

Improvement of Uncertainty Assessment of Discharge Estimated by Velocity-Area Method

The present study was conducted to re-estimate the factors needed for the velocity-area method previously provided by ISO through precise actual scale experiments in order to verify the appropriateness of the errors of the individual factors presented by ISO 748 and ISO 1088. For this, a steady-state flow of a flow velocity of approximately 1 m/s, 7 m wide, and 1 m deep, was maintained in the mild slope channel located at the River Experiment Center (Andong) of the Korea Institute of Construction Technology. Under this condition, the objective was to measure the flow velocity very precisely with respect to the space by using a micro-ADV having a high accuracy of flow velocity measurement. The water depth was precisely measured before the generation of the flow by using Total Station. The ISO regulations and the results of the present experiment were applied to three different conditions. The uncertainty assessed by applying the results of the present experiment exceeded twice that of the uncertainty estimated by applying the uncertainty factors provided by ISO. The uncertainty of the lateral gap between measurement lines and the number of measurement points in the depth direction was dependent on the scale of rivers. However, ISO may have presented the uncertainty factors analyzed from the data obtained from a wide range of river scales. Therefore, the discharge estimated by the velocity-area method may be dependent on the scale of rivers. The errors of the individual factors of the velocity-area method derived from the present study may be applied to the estimation of the uncertainty of the discharge calculated by the velocity-area method in small rivers

Improvement of Uncertainty Assessment of Discharge Estimated by Velocity-Area Method

The present study was conducted to re-estimate the factors needed for the velocity-area method previously provided by ISO through precise actual scale experiments in order to verify the appropriateness of the errors of the individual factors presented by ISO 748 and ISO 1088. For this, a steady-state flow of a flow velocity of approximately 1 m/s, 7 m wide, and 1 m deep, was maintained in the mild slope channel located at the River Experiment Center (Andong) of the Korea Institute of Construction Technology. Under this condition, the objective was to measure the flow velocity very precisely with respect to the space by using a micro-ADV having a high accuracy of flow velocity measurement. The water depth was precisely measured before the generation of the flow by using Total Station. The ISO regulations and the results of the present experiment were applied to three different conditions. The uncertainty assessed by applying the results of the present experiment exceeded twice that of the uncertainty estimated by applying the uncertainty factors provided by ISO. The uncertainty of the lateral gap between measurement lines and the number of measurement points in the depth direction was dependent on the scale of rivers. However, ISO may have presented the uncertainty factors analyzed from the data obtained from a wide range of river scales. Therefore, the discharge estimated by the velocity-area method may be dependent on the scale of rivers. The errors of the individual factors of the velocity-area method derived from the present study may be applied to the estimation of the uncertainty of the discharge calculated by the velocity-area method in small rivers

Cancer Resistance to Immunotherapy: Molecular Mechanisms and Tackling Strategies

Cancer immunotherapy has fundamentally altered cancer treatment; however, its efficacy is limited to a subset of patients in most clinical settings. The immune system plays a key role in cancer progression from tumor initiation to the metastatic state. Throughout the treatment course, communications between the immune cells in the tumor microenvironment and the immune macroenvironment, as well as interactions between the immune system and cancer cells, are dynamic and constantly evolving. To improve the clinical benefit for patients who do not respond completely to immunotherapy, the molecular mechanisms of resistance to immunotherapy must be elucidated in order to develop effective strategies to overcome resistance. In an attempt to improve and update the current understanding of the molecular mechanisms that hinder immunotherapy, we discuss the molecular mechanisms of cancer resistance to immunotherapy and the available treatment strategies

APSec1.0: Innovative Security Protocol Design with Formal Security Analysis for the Artificial Pancreas System

The Medical Internet-of-Things (MIoT) has developed revolutionary ways of delivering medical care to patients. An example system, showing increasing demand, is the artificial pancreas system that offers convenience and reliable support care to patients with Type 1 Diabetes. Despite the apparent benefits, the system cannot escape potential cyber threats that may worsen a patient’s condition. The security risks need immediate attention to ensure the privacy of the patient and preserve safe functionality. Motivated by this, we proposed a security protocol for the APS environment wherein support to essential security requirements is guaranteed, the security context negotiation is resource-friendly, and the protocol is resilient to emergencies. Accordingly, the security requirements and correctness of the design protocol were formally verified using BAN logic and AVISPA, and proved its feasibility through the emulation of APS in a controlled environment using commercial off-the-shelf devices. Moreover, the results of our performance analysis indicate that the proposed protocol is more efficient than the other existing works and standards

Sensing Characteristics of SARS-CoV-2 Spike Protein Using Aptamer-Functionalized Si-Based Electrolyte-Gated Field-Effect Transistor (EGT)

The sensing responses of SARS-CoV-2 spike protein using top-down-fabricated Si-based electrolyte-gated transistors (EGTs) have been investigated. An aptamer was employed as a receptor for the SARS-CoV-2 spike protein. The EGT demonstrated excellent intrinsic characteristics and higher sensitivity in the subthreshold regime compared to the linear regime. The limit of detection (LOD) was achieved as low as 0.94 pg/mL and 20 pg/mL for the current and voltage sensitivity, respectively. To analyze the sensing responses of EGT in detecting the aptamer–SARS-CoV-2 spike protein conjugate, a lumped-capacitive model with the presence of an effective dipole potential and an effective capacitance of the functionalized layer component was employed. The aptamer-functionalized EGT showed high sensitivity even in 10 mM phosphate-buffered saline (PBS) solution. These results suggest that Si-based EGTs are a highly promising method for detecting SARS-CoV-2 spike proteins

Low-Temperature Effects on the Growth and Phytochemical Properties of Wheat Sprouts

Sprouting is associated with nutritional value, as microgreens stimulate the accumulation of health-promoting phytochemicals. The purpose of this study was to examine the growth rates and cell protection activity against oxidative stress in sprouts of seven wheat varieties, and to investigate the influence of low temperatures on their phytochemical characteristics. Among the seven wheat varieties (five Korean varieties, Australian standard white, and Chinese wild-type wheat germplasm), purple wheat (Ariheuk) had the fastest growth pattern for 8 days and provided the most protection to skin cells and hepatocytes against oxidative stress. Following low-temperature treatment (<4 °C) for 1–4 days, cold exposure had a similar effect on the growth of purple wheat sprouts during an 8-day period. However, growth was negatively affected by exposure to low temperatures for more than 5 days. Purple wheat sprouts treated with low temperatures for 4 days had considerably higher total polyphenol and total flavonoid contents, as well as a higher antioxidant capacity than untreated wheat sprouts. These findings suggest that low-temperature treatment promotes the expression of phytochemicals in purple wheat sprouts. Thus, purple wheat sprouts are considered a high-value crop that could be used as a functional food material

Low-Temperature Effects on the Growth and Phytochemical Properties of Wheat Sprouts

Sprouting is associated with nutritional value, as microgreens stimulate the accumulation of health-promoting phytochemicals. The purpose of this study was to examine the growth rates and cell protection activity against oxidative stress in sprouts of seven wheat varieties, and to investigate the influence of low temperatures on their phytochemical characteristics. Among the seven wheat varieties (five Korean varieties, Australian standard white, and Chinese wild-type wheat germplasm), purple wheat (Ariheuk) had the fastest growth pattern for 8 days and provided the most protection to skin cells and hepatocytes against oxidative stress. Following low-temperature treatment (&lt;4 &deg;C) for 1&ndash;4 days, cold exposure had a similar effect on the growth of purple wheat sprouts during an 8-day period. However, growth was negatively affected by exposure to low temperatures for more than 5 days. Purple wheat sprouts treated with low temperatures for 4 days had considerably higher total polyphenol and total flavonoid contents, as well as a higher antioxidant capacity than untreated wheat sprouts. These findings suggest that low-temperature treatment promotes the expression of phytochemicals in purple wheat sprouts. Thus, purple wheat sprouts are considered a high-value crop that could be used as a functional food material

CD47 Expression Predicts Unfavorable Prognosis in Clear Cell Renal Cell Carcinoma after Curative Resection

The role of CD47 expression as a &lsquo;do not eat me&rsquo; signal that inhibits phagocytosis of tumor cells by macrophages is well established. Immune checkpoint therapy that targets CD47 has been successful in preclinical trials and is currently undergoing clinical investigation for various human malignancies. Here, the clinicopathological correlation with CD47 expression in clear cell renal cell carcinoma (ccRCC) was explored. CD47 expression was evaluated by immunohistochemical staining in tissue microarray sections of 235 ccRCC tissues. CD47 expression was observed in 28 (11.9%) of 235 ccRCC tissues and was significantly associated with higher WHO/ISUP grade (p = 0.001), frequent lymphovascular invasion (p = 0.036), frequent renal vein thrombus (p = 0.018), frequent sinus fat invasion (p = 0.004), frequent sarcomatous change (p = 0.001), higher pT stage (p = 0.002), higher pN stage (p = 0.002), higher pM stage (p &lt; 0.001), and advanced American Joint Committee on Cancer stage (p = 0.002). In the survival analyses, positive CD47 expression was associated with cancer-specific survival (p = 0.003). However, positive CD47 expression was not associated with recurrence-free survival. In conclusion, CD47 expression was associated with adverse clinicopathological parameters and cancer-specific survival in patients with ccRCC