IL4 receptor targeting enables nab-paclitaxel to enhance reprogramming of M2-type macrophages into M1-like phenotype via ROS-HMGB1-TLR4 axis and inhibition of tumor growth and metastasis.

Rationale: Nab-paclitaxel (Abx) is widely employed in malignant tumor therapy. In tumor cells and pro-tumoral M2-type macrophages, the IL4 receptor (IL4R) is upregulated. This study aimed to elucidate the selective delivery of Abx to M2-type macrophages by targeting IL4R and reprogramming them into an anti-tumoral M1-type. Methods: Abx was conjugated with the IL4R-binding IL4RPep-1 peptide using click chemistry (IL4R-Abx). Cellular internalization, macrophage reprogramming and signal pathways, and tumor growth and metastasis by IL4R-Abx were examined. Results: IL4R-Abx was internalized into M2 macrophages more efficiently compared to the unmodified Abx and control peptide-conjugated Abx (Ctrl-Abx), which was primarily inhibited using an anti-IL4R antibody and a receptor-mediated endocytosis inhibitor compared with a macropinocytosis inhibitor. IL4R-Abx reprogrammed the M2-type macrophages into M1-like phenotype and increased reactive oxygen species (ROS) levels and extracellular release of high mobility group box 1 (HMGB1) in M2 macrophages at higher levels than Abx and Ctrl-Abx. The conditioned medium of IL4R-Abx-treated M2 macrophages skewed M2 macrophages into the M1-like phenotype, in which an anti-HMGB1 antibody and a toll-like receptor 4 (TLR4) inhibitor induced a blockade. IL4R-Abx accumulated at tumors, heightened immune-stimulatory cells while reducing immune-suppressing cells, and hampered tumor growth and metastasis in mice more efficiently than Abx and Ctrl-Abx. Conclusions: These results indicate that IL4R-targeting allows enhancement of M2-macrophage shaping into M1-like phenotype by Abx through the ROS-HMGB1-TLR4 axis, improvement of antitumor immunity, and thereby inhibition of tumor growth and metastasis, presenting a new approach to cancer immunotherapy.

Partial Venous Inflow Occlusion under Mild Hypothermia for Membranectomy in a Dog with Cor Triatriatum Dexter.

Cor triatriatum dexter (CTD) is an uncommon congenital cardiac anomaly in dogs. This case report describes successful membranectomy for CTD via partial venous inflow occlusion under mild hypothermia in a dog. A 7-month-old intact male mixed-breed dog weighing 20.5 kg presented with a history of abdominal distention, lethargy, and anorexia. Clinical examination, radiography, echocardiography, microbubble testing, and computed tomography revealed a remnant right atrium membrane obscuring the venous blood inflow from the vena cava. Considering the potential risk of re-stenosis following interventional treatment, curative resection involving surgical membranectomy via venous inflow occlusion was performed. By performing partial venous inflow occlusion under mild hypothermia (34.5 °C), sufficient time was obtained to explore the defect and resect the remnant membrane. The dog recovered without any complications, and the clinical signs were relieved. This case illustrates that partial venous inflow occlusion under mild hypothermia is feasible for achieving curative resection of cor triatriatum dexter in dogs.

Development and Quality Characteristics of Elderly-Friendly Pulpo a La Gallega Prepared Using Texture-Modified Octopus (Octopus vulgaris) Arms.

Considering the need for developing new senior-friendly processed seafood, this study aimed to develop octopus pulpo with high preference and excellent quality characteristics for elderly individuals by optimizing the vinegar immersion and sous vide softening treatment conditions for octopus (Octopus vulgaris) arms. The optimal sous vide heating temperature (70.0-100.0 °C), time (69.5-170.5 min), and vinegar concentration (0.2-0.8%) were established using response surface methodology (RSM). The pulpo prototype was produced using an octopus arm softened under optimal conditions and seasoned with a potato and olive oil sauce. The physicochemical and nutritional properties of the prototype were evaluated, followed by sensory evaluation and safety assessments. The hardness of softened octopuses obtained by 0.48% vinegar immersion and sous vide treatment (84.3 °C, 139.8 min), determined using RSM, was 394.5 × 1000 N/m2, showing a reduction of 83.0%; this was confirmed by electron microscopic observation. The texture of the pulpo prototype with softened octopus arms showed the highest preference (8.4 points) and high physicochemical and nutritional properties. Overall, the octopus pulpo a La Gallega prototype produced using texture-modified octopus arms was suitable for consumption by elderly people with chewing disorders and could help improve their quality of life.

Peptides as multifunctional players in cancer therapy.

Peptides exhibit lower affinity and a shorter half-life in the body than antibodies. Conversely, peptides demonstrate higher efficiency in tissue penetration and cell internalization than antibodies. Regardless of the pros and cons of peptides, they have been used as tumor-homing ligands for delivering carriers (such as nanoparticles, extracellular vesicles, and cells) and cargoes (such as cytotoxic peptides and radioisotopes) to tumors. Additionally, tumor-homing peptides have been conjugated with cargoes such as small-molecule or chemotherapeutic drugs via linkers to synthesize peptide-drug conjugates. In addition, peptides selectively bind to cell surface receptors and proteins, such as immune checkpoints, receptor kinases, and hormone receptors, subsequently blocking their biological activity or serving as hormone analogs. Furthermore, peptides internalized into cells bind to intracellular proteins and interfere with protein-protein interactions. Thus, peptides demonstrate great application potential as multifunctional players in cancer therapy.

How Important Is Behavioral Change during the Early Stages of the COVID-19 Pandemic? A Mathematical Modeling Study.

How important is the speed and intensity of behavioral change due to government policies, such as enhanced social distancing or lockdown, when an emerging infectious disease occurs? In this study, we introduce a deterministic SEIR model considering the behavior-changed susceptible group to investigate the effect of the speed and intensity of behavioral change on the transmission dynamics of COVID-19. We used epidemiological data from South Korea and Italy for the simulation study, because South Korea and Italy were the first countries to report an outbreak of COVID-19 after China and the prevention and response policy of each government were similar during the first outbreak of COVID-19. Simulation results showed that it took approximately twenty fewer days in Korea than in Italy until 90% of susceptible individuals changed their behavior during the first outbreak. It was observed that the behavior-changed susceptible individuals reduced the COVID-19 transmission rate by up to 93% in Korea and 77% in Italy. Furthermore, if the intensity and speed of behavioral change in Italy were the same as in Korea, the expected number of cumulative confirmed cases would have been reduced by approximately 95%, from 210,700 to 10,700, until the end of the lockdown period. We assumed that behavioral change is influenced by the number of confirmed cases and does not take into account social and cultural differences, as well as the state of the healthcare system, between the two countries. Our mathematical modeling showed how important the high intensity and fast speed of behavioral change to reduce the number of confirmed cases in the early period of an epidemic are.

The effect of initiator encapsulation on methyl methacrylate polymerization by isothermal differential scanning calorimetry.

Microcapsules containing initiator of cumene hydroperoxide or tert-butyl peroxy-2-ethylhexanoate as core material and polyurea as shell material were prepared by condensation polymerisation in oil-in-water emulsion at different agitation speeds. And their effects on the polymerisation of methyl methacrylate were investigated by isothermal differential scanning calorimetry. In comparison to unencapsulated initiators, the use of encapsulated initiators significantly delayed the reaction, reduced the maximum heat flow, relatively reduced the maximum reaction rate, and made the conversion smaller. In addition, the encapsulated initiator shortened the time lag, increased the heat flow at the maximum point as the reaction temperature increased, and further delayed the appearance time of the maximum reaction point as the agitation speed decreased. The theoretical values calculated by the modified Kamal model, including the nth-order reaction formula and the autoacceleration reaction, were in good agreement with our experimental data. We observed the more prominent autoacceleration reaction at a higher conversion.

Ebola virus disease outbreak in Korea: use of a mathematical model and stochastic simulation to estimate risk.

OBJECTIVES: According to the World Health Organization, there have been frequent reports of Ebola virus disease (EVD) since the 2014 EVD pandemic in West Africa. We aim to estimate the outbreak scale when an EVD infected person arrives in Korea. METHODS: Western Africa EVD epidemic mathematical model SEIJR or SEIJQR was modified to create a Korean EVD outbreak model. The expected number of EVD patients and outbreak duration were calculated by stochastic simulation under the scenarios of Best case, Diagnosis delay, and Case missing. RESULTS: The 2,000 trials of stochastic simulation for each scenario demonstrated the following results: The possible median number of patients is 2 and the estimated maximum number is 11 when the government intervention is proceeded immediately right after the first EVD case is confirmed. With a 6-day delay in diagnosis of the first case, the median number of patients becomes 7, and the maximum, 20. If the first case is missed and the government intervention is not activated until 2 cases of secondary infection occur, the median number of patients is estimated at 15, and the maximum, at 35. CONCLUSIONS: Timely and rigorous diagnosis is important to reduce the spreading scale of infection when a new communicable disease is inflowed into Korea. Moreover, it is imperative to strengthen the local surveillance system and diagnostic protocols to avoid missing cases of secondary infection.

Complete Chloroplast Genome of Nicotiana otophora and its Comparison with Related Species.

Nicotiana otophora is a wild parental species of Nicotiana tabacum, an interspecific hybrid of Nicotiana tomentosiformis and Nicotiana sylvestris. However, N. otophora is least understood as an alternative paternal donor. Here, we compared the fully assembled chloroplast (cp) genome of N. otophora and with those of closely related species. The analysis showed a cp genome size of 156,073 bp and exhibited a typical quadripartite structure, which contains a pair of inverted repeats separated by small and large single copies, containing 163 representative genes, with 165 microsatellites distributed unevenly throughout the genome. Comparative analysis of a gene with known function across Nicotiana species revealed 76 protein-coding sequences, 20 tRNA sequences, and 3 rRNA sequence shared between the cp genomes. The analysis revealed that N. otophora is a sister species to N. tomentosiformis within the Nicotiana genus, and Atropha belladonna and Datura stramonium are their closest relatives. These findings provide a valuable analysis of the complete N. otophora cp genome, which can identify species, elucidate taxonomy, and reconstruct the phylogeny of genus Nicotiana.

Phytotoxic mechanisms of bur cucumber seed extracts on lettuce with special reference to analysis of chloroplast proteins, phytohormones, and nutritional elements.

Bioherbicides from plant extracts are an effective and environmentally friendly method to prevent weed growth. The present investigation was aimed at determining the inhibitory effect of bur cucumber seed extracts (BSE) on lettuce plant growth. Bur cucumber seeds were ground with water, and two different concentrations of seed extracts (10% and 20%) were prepared and applied to lettuce plants. Decreased plant height, number of leaves, leaf length, leaf width, anProd. Type: FTPd leaf area were found in lettuce exposed to BSE as compared with controls. A significant reduction in lettuce biomass was observed in 20% BSE-treated plants due to the presence of higher amounts of phenolic content in the extracts. Moreover, a significant inhibitory chemical, 2-linoleoyl glycerol, was identified in BSE extracts. The mechanism of plant growth inhibition was assayed in lettuce proteins by 2-dimensional electrophoresis (2-DE) and the LC-MS/MS method. In total, 57 protein spots were detected in plants treated with 20% BSE and control plants. Among these, 39 proteins were down-regulated and 18 proteins were up-regulated in plants exposed to 20% BSE as compared with controls. The presence of low levels of chlorophyll a/b binding protein and oxygen-evolving enhancer protein 1 in BSE-exposed plants reduced photosynthetic pigment synthesis and might be a reason for stunted plant growth. Indeed, the plant-growth stimulating hormone gibberellin was inhibited, and synthesis of stress hormones such as abscisic acid, jasmonic acid, and salicylic acid were triggered in lettuce by the effects of BSE. Uptake of essential nutrients, Ca, Fe, Mg, K, S, and Mo, was deficient and accumulation of the toxic ions Cu, Zn, and Na was higher in BSE-treated plants. The results of this study suggest that extracts of bur cucumber seeds can be an effective eco-friendly bioherbicide for weed control that work by inhibiting mechanisms of photosynthesis and regulating phytohormones and nutritional elements.

Optimal intervention strategy for prevention tuberculosis using a smoking-tuberculosis model.

In this paper, we developed a dynamic model of smoking-tuberculosis (TB) transmission in South Korea, and investigated the effects of control strategies on the number of incidence of TB using optimal control theory. Model parameters regarding TB and smoking are estimated through least-squares fitting to real data. We considered three TB controls (distancing, case-finding, and case-holding) and two smoking controls (distancing and quitting), in order to minimize the number of exposed and infectious individuals and the cost of control. Numerical simulations for the various control strategies highlight that implementing the smoking controls, not with TB controls, can effectively reduce the incidence of TB transmission.

Traumatic atypical tetraplegia without radiologic abnormalities including magnetic resonance imaging in an adult: a case report.

Although spinal cord injury without radiographic abnormality (SCIWORA) literally refers to the specific type of spinal cord injury, however, some extents of spinal cord injuries can be detected by magnetic resonance imaging (MRI) in most of cases. We introduce an atypical case of spinal cord injury without radiologic abnormality. A 42-year-old male tetraplegic patient underwent MRI and computed tomography, and no specific lesions were found in any segments of the spinal cord. Moreover, the tetraplegic patient showed normal urodynamic function despite severe paralysis and absent somatosensory evoked potentials from the lower limbs.

Anterior cervical osteophytes causing Dysphagia and paradoxical vocal cord motion leading to dyspnea and dysphonia.

Anterior cervical osteophytes are common and usually asymptomatic in elderly people. Due to mechanical compressions, inflammations, and tissues swelling of osteophytes, patients may be presented with multiple complications, such as dysphagia, dysphonia, dyspnea, and pulmonary aspiration. Paradoxical vocal cord motion is an uncommon disease characterized by vocal cord adductions during inspiration and/or expiration. This condition can create shortness of breath, wheezing, respiratory stridor or breathy dysphonia. We report a rare case demonstrating combined symptoms of dyspnea, dysphonia as well as dysphagia at the same time in a patient with asymptomatic anterior cervical osteophytes. Moreover, this is the first report demonstrating that anterior osteophytes can be a possible etiological factor for paradoxical vocal cord motion that induces serious respiratory symptoms.