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Taste buds, the neuroepithelial organs responsible for the detection of gustatory stimuli in the oral cavity, arise from stem/progenitor cells among nearby basal keratinocytes. Using genetic lineage tracing, Lgr5 and Lgr6 were suggested as the specific markers for the stem/progenitor cells of taste buds, but recent evidence implied that taste buds may arise even in the absence of these markers. Thus, we wanted to verify the genetic lineage tracing of lingual Lgr5- and Lgr6-expressing cells. Unexpectedly, we found that antibody staining revealed more diverse Lgr5-expressing cells inside and outside the taste buds of circumvallate papillae than was previously suggested. We also found that, while tamoxifen-induced genetic recombination occurred only in cells expressing the Lgr5 reporter GFP, we did not see any increase in the number of recombined daughter cells induced by consecutive injections of tamoxifen. Similarly, we found that cells expressing Lgr6, another stem/progenitor cell marker candidate and an analog of Lgr5, also do not generate recombined clones. In contrast, Lgr5-expressing cells in fungiform papillae can transform into Lgr5-negative progeny. Together, our data indicate that lingual Lgr5- and Lgr6-expressing cells exhibit diversity in their capacity to transform into Lgr5- and Lgr6-negative cells, depending on their location. Our results complement previous findings that did not distinguish this diversity.

This study investigates the variations in the microstructure and mechanical properties of a rolled Mg-3.0Al-0.8Zn-0.3Mn (AZ31, wt.%) alloy caused by ultrasonic nanocrystal surface modification (UNSM) treatment and subsequent annealing. The UNSM-treated material has a gradient microstructure characterized by a nanoscale grain region overlying a twinned region. The nanoscale grain region close to the surface has extremely high strain energy, while the twinned region contains abundant {10–12} twins. Severe plastic deformation near the surface due to UNSM treatment leads to the formation of ultrafine grains and an increase in dislocation density, thereby remarkably improving the hardness and strength of the material. However, the excessive dislocation density reduces the tensile ductility. During subsequent annealing, static recrystallization occurs rapidly in the nanoscale grain region, and partial grain-boundary migration and dislocation recovery occur in the twinned region. Consequently, a gradient microstructure is formed along the thickness direction in the material subjected to UNSM treatment and subsequent annealing, thereby resulting in a tensile yield strength of 172 MPa, an ultimate tensile strength of 259 MPa, and an elongation of 15.4%. Notably, these values are higher than those of the as-rolled material, which are 132 MPa, 246 MPa, and 13.4%, respectively. This demonstrates that the sequential UNSM and annealing process results in a simultaneous improvement in the strength and ductility of the material. The strengthening mechanisms and fracture behavior are comprehensively discussed in this study.

This study investigates the effect of the deformation mode on the precipitation behavior of an extruded Mg–8.0Al–0.5Zn–0.2Mn (AZ80) alloy. The alloy samples are compared after the application of 3.5% tension and 3.5% compression along the extrusion direction to induce slip-dominant and twinning-dominant deformation modes, respectively. The pre-compressed (PC) sample, which contained numerous {10–12} tension twins, has a reduced grain size and a higher internal strain than the pre-tensioned (PT) sample, which is attributed to the inherent internal strain that occurs during the formation and growth of the twins. As a result, the precipitation behavior of the PC sample is accelerated, leading to its short peak aging time of 32 h, which is lower than those of the PT and as-extruded samples (48 and 100 h, respectively). Furthermore, fine continuous precipitates (CPs) rapidly form within the {10–12} twins, contributing to the enhanced hardness. Discontinuous precipitates (DPs), which have a hardness comparable to the CP-containing twinned regions, in the PC sample experience less coarsening during aging than those in the PT sample due to growth inhibition by the {10–12} twins. Ultimately, the {10–12} twins generated under the twinning-dominant deformation condition lead to enhanced precipitation behaviors, including the preferential formation and refinement of CPs and the suppressed coarsening of DPs. Consequently, pre-deformation that occurs {10–12} twinning exhibits more pronounced effects on precipitation acceleration and microstructural modification than slip-inducing pre-deformation.

Purpose This study assessed the benefits of quality threshold (QT) implementation for liver shear wave elastography (SWE) in children during free breathing. Methods The QT, which adjusts the SWE map display based on shear wave quality, was set at 55%. Phantom measurements (PMs) were taken with a fixed probe using QT (termed PM-1); a moving probe without QT (PM-2); and a moving probe with QT (PM-3). Each measurement was subjected to random samplings of various sizes. Clinical measurements (CMs) were obtained from children with biliary atresia using following protocols: CM-1, manually defined regions of interest (ROIs); CM-2, default ROIs without QT; and CM-3, default ROIs with QT. Elasticity measurements were compared across fibrosis grades, and color patterns on the SWE maps were analyzed. Results In the phantom experiments, the moving probe produced lower elasticity measurements; this difference decreased upon QT application. With the moving probe, random sampling indicated fewer interquartile range-to-median ratios exceeding 30% upon QT application (4% vs. 14% when five values were sampled, P=0.004). In clinical experiments, QT improved the differentiation of fibrosis grade in patients over 5 years old, with a significant difference between moderate and severe fibrosis (P=0.004). Elasticity variability was positively correlated with fibrosis grade (τ=0.376, P

This study investigated the influence of the addition of Al to a Mg–7Bi (B7, wt%) alloy, particularly its recrystallization behavior during extrusion and its resulting mechanical properties. The addition of 2 wt% Al to the B7 alloy resulted in a lower grain size, a reduction in the number density of fine Mg3Bi2 particles, and a higher area fraction of relatively coarse Mg3Bi2 particles in the extrusion billet. These microstructural changes increased the nucleation sites for recrystallization, reduced the Zener pinning effect, and enhanced particle-stimulated nucleation, all of which promoted dynamic recrystallization behavior during extrusion. As a result, the area fraction of recrystallized grains in the extruded alloy increased from 77 % to 94 %. The extruded B7 alloy exhibited a strong fiber texture, whereas the extruded Mg–7Bi–2Al (BA72) alloy had a weak – texture, which was attributed to the minimal presence of unrecrystallized grains and the dispersed orientation of the recrystallized grains. The tensile yield strength (TYS) of the extruded BA72 alloy was higher than that of the extruded B7 alloy (170 and 124 MPa, respectively), which resulted from the enhanced grain-boundary and solid-solution strengthening effects. The tensile elongation (EL) of the BA72 alloy also exceeded that of the B7 alloy (20.3 % and 6.1 %, respectively), the result of the uniform formation of fine twins under tension in the former and the formation of a few coarse twins among the unrecrystallized grains in the latter. Consequently, the addition of a small amount of Al to the B7 alloy significantly improved both the strength and ductility of the extruded alloy, resulting in a remarkable increase in the product of the TYS and EL from 756 to 3451 MPa% and expanding its potential range of applications as a lightweight extruded structural component.

Hepatocellular carcinoma (HCC) comprises the majority of primary liver cancers and possesses a low 5-year survival rate when in the advanced stages. Anillin (ANLN), a key player in cell growth and cytokinesis, is implicated in HCC development. Currently, no treatment agents are known to suppress ANLN. Analysis of The Cancer Genome Atlas data showed that high ANLN expression is associated with poor prognosis and survival in HCC patients. ANLN knockdown was shown to inhibit proliferation, cell cycle progression, and PD-L1 expression in liver cancer cells. The antipsychotic drug penfluridol was identified to suppress ANLN expression in the Connectivity Map analysis. Penfluridol downregulated ANLN at both the mRNA and protein levels, leading to G2/M cell cycle arrest and reduced colony formation in liver cancer cells. Mechanistically, penfluridol inhibited the transcription factor MYC from binding to an E-box motif in the ANLN promoter. This process was mediated by penfluridol-induced upregulation of NRF2, which competitively bound and sequestered MYC away from the ANLN promoter. Penfluridol inhibited the interaction between NRF2 and KEAP1, increasing NRF2. In a syngeneic mouse model, penfluridol suppressed liver tumour growth accompanied by increased NRF2 and decreased MYC and ANLN expression. These findings suggest penfluridol can be applied as the first ANLN blocker to modulate the MYC/NRF2/KEAP1 axis.

BackgroundSince its introduction, telemedicine for patients with chronic diseases has been studied in various clinical settings. However, there is limited evidence of the effectiveness and medical safety of the nationwide adoption of telemedicine. ObjectiveThis study aimed to analyze the effects of telemedicine on chronic diseases during the COVID-19 pandemic under a temporary telemedicine policy in South Korea using national claims data. MethodsHealth insurance claims data were extracted over 2 years: 1 year before (from February 24, 2019, to February 23, 2020) and 1 year after the policy was implemented (from February 24, 2020, to February 23, 2021). We included all patients who used telemedicine at least once in the first year after the policy was implemented and compared them with a control group of patients who never used telemedicine. The comparison focused on health care use; the medication possession ratio (MPR); and admission rates to general wards (GWs), emergency departments (EDs), and intensive care units (ICUs) using difference-in-differences analysis. A total of 4 chronic diseases were targeted: hypertension, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), and common mental disorders. ResultsA total of 1,773,454 patients with hypertension; 795,869 patients with DM; 37,460 patients with COPD; and 167,084 patients with common mental disorders were analyzed in this study. Patients diagnosed with hypertension or DM showed increased MPRs without an increase in GW, ED, or ICU admission rates during the policy year. Moreover, patients in the DM group who did not use telemedicine had higher rates of ED, GW, and ICU admissions, and patients in the hypertension group had higher rates of GW or ICU admissions after 1 year of policy implementation. This trend was not evident in COPD and common mental disorders. ConclusionsThe temporary telemedicine policy was effective in increasing medication adherence and reducing admission rates for patients with hypertension and DM; however, the efficacy of the policy was limited for patients with COPD and common mental disorders. Future studies are required to demonstrate the long-term effects of telemedicine policies with various outcome measures reflecting disease characteristics.

Abstract The development of chemoresistance is a major challenge in the treatment of several types of cancers in clinical settings. Stemness and chemoresistance are the chief causes of poor clinical outcomes. In this context, we hypothesized that understanding the signaling pathways responsible for chemoresistance in cancers is crucial for the development of novel targeted therapies to overcome drug resistance. Among the aberrantly activated pathways, the PI3K-Akt/Wnt/β-catenin signaling pathway is clinically implicated in malignancies such as colorectal cancer (CRC) and glioblastoma multiforme (GBM). Aberrant dysregulation of phospholipase D (PLD) has been implicated in several malignancies, and oncogenic activation of this pathway facilitates tumor proliferation, stemness, and chemoresistance. Crosstalk involving the PLD and Wnt/β-catenin pathways promotes the progression of CRC and GBM and reduces the sensitivity of cancer cells to standard therapies. Notably, both pathways are tightly regulated and connected at multiple levels by upstream and downstream effectors. Thus, gaining deeper insights into the interactions between these pathways would help researchers discover unique therapeutic targets for the management of drug-resistant cancers. Here, we review the molecular mechanisms by which PLD signaling stimulates stemness and chemoresistance in CRC and GBM. Thus, the current review aims to address the importance of PLD as a central player coordinating cross-talk between the PI3K/Akt and Wnt/β-catenin pathways and proposes the possibility of targeting these pathways to improve cancer therapy and overcome drug resistance.

Breast lymphomas are rare, malignant breast neoplasms with a heterogeneous pattern of clinical symptoms. Burkitt’s lymphoma is a rare, highly aggressive, and rapidly growing B-cell non-Hodgkin lymphoma. We report about a 27-year-old woman diagnosed as having secondary breast Burkitt’s lymphoma, probably originating from the stomach, with multiple distant metastases. Breast ultrasonography revealed multiple, variable sized, heterogeneous masses with posterior acoustic enhancement and echogenic rims. These imaging findings may sometimes overlap with those of other breast malignancies. However, unlike other breast malignancies, lymphoma can be diagnosed by biopsy and does not require surgical excision. To avoid unnecessary treatment, radiologists and clinicians should be aware of the characteristic imaging features of breast lymphomas.

This study investigates the influence of extrusion conditions on the microstructure and tensile properties of Mg–6Al–0.3Mn–0.3Ca–0.2Y (SEN6) alloy, which is processed at various extrusion temperatures and ratios. An increase in both the extrusion temperature and ratio facilitates dynamic recrystallization during hot extrusion by enhancing thermal and strain energies, increasing the area fraction of recrystallized grains within the extruded material. As either the extrusion temperature or ratio increases, lattice rotation within the recrystallized grains intensifies, resulting in a stronger basal texture in the extruded material. During extrusion, the undissolved Al2Y, Al8Mn4Y, and Al2Ca particles within the billets are partially fragmented and realigned along the extrusion direction. However, the quantity, size, and dispersion of these particles are largely unaffected by variations in extrusion temperature and ratio. The tensile yield strength of the extruded material shows a positive correlation with increasing extrusion temperature and ratio, predominantly due to enhanced texture hardening. Specifically, the tensile yield strength of the material extruded at 400 °C with an extrusion ratio of 25 is 23.2 MPa higher than that of the material extruded at 300 °C with an extrusion ratio of 10. Despite the presence of non-recrystallized grains in materials extruded at the lower extrusion ratio of 10, compression and double twins form uniformly throughout the material during tension, as the widths of non-recrystallized grains are similar to those of recrystallized grains. Consequently, all extruded materials exhibit high tensile elongations, exceeding 20%.

Abstract Sargassum horneri (S. horneri), a brown seaweed excessively proliferating along Asian coastlines, are damaging marine ecosystems. Thus, this study aimed to enhance nutritional value of S. horneri through lactic acid bacteria fermentation to increase S. horneri utilization as a functional food supplement, and consequently resolve coastal S. horneri accumulation. S. horneri supplemented fermentation was most effective with Lactiplantibacillus pentosus SH803, thus this product (F-SHWE) was used for further in vitro studies. F-SHWE normalized expressions of oxidative stress related genes NF-κB, p53, BAX, cytochrome C, caspase 9, and caspase 3, while non-fermented S. horneri (SHWE) did not, in a H2O2-induced HT-29 cell model. Moreover, in an LPS-induced HT-29 cell model, F-SHWE repaired expressions of inflammation marker genes ZO1, IL1β, IFNγ more effectively than SHWE. For further functional assessment, F-SHWE was also treated in 3T3-L1 adipocytes. As a result, F-SHWE decreased lipid accumulation, along with gene expression of adipogenesis markers PPARγ, C/EBPα, C/EBPβ, aP2, and Lpl; lipogenesis markers Lep, Akt, SREBP1, Acc, Fas; inflammation markers IFN-γ and NF-κB. Notably, gene expression of C/EBPβ, IFN-γ and NF-κB were suppressed only by F-SHWE, suggesting the enhancing effect of fermentation on obesity-related properties. Compositional analysis attributed the protective effects of F-SHWE to acetate, an organic acid significantly higher in F-SHWE than SHWE. Therefore, F-SHWE is a novel potential anti-obesity agent, providing a strategy to reduce excess S. horneri populations along marine ecosystems.

Abstract Background To investigate the prognosis of the remaining fetus in twin pregnancy after experiencing one fetal demise in the first trimester according to the location of the demised fetus. Methods This was a retrospective study of twin pregnancies with one fetal demise after the first trimester (14 weeks of gestation) delivered between September 2004 and September 2022. The study population was divided into two groups based on the location of the demised fetus as determined by the last recorded ultrasonography results: Group 1 included twin pregnancies where the presenting fetus was demised (n = 36) and Group 2 included twin pregnancies where the non-presenting fetus was demised (n = 44). The obstetric and neonatal outcomes were also reviewed. Results A total of 80 pregnant women were included. The median gestational age for the diagnosis of fetal demise was 24.1 weeks. The gestational age of the demised fetus was not different between Groups 1 and 2; however, the gestational age of the remaining fetus at delivery was significantly earlier in Group 1 than it was in Group 2 (33.8 vs. 37.3 weeks, P = .004). The rate of preterm birth before 28 weeks was almost five times higher in Group 1 than in Group 2 (22.2% vs. 4.5%, P = .037). Regression analysis demonstrated significant differences between Groups 1 and 2. Respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, retinopathy of prematurity, and jaundice were more common in Group 1 than in Group 2; however, the association was not significant after adjusting for gestational age at delivery. Conclusions When the presenting fetus is demised in a twin pregnancy, the remaining fetus tends to be delivered earlier than when the non-presenting fetus is demised.

Abstract In this retrospective study spanning from 2002 to 2019, we analyzed data from 355,277 Korean patients diagnosed with atopic dermatitis (AD) through the National Health Insurance System. Our objective was to comprehensively analyze the trends in prevalence, severity profiles, and treatment approaches for AD in Korea over this 18-year period. Initially, AD prevalence stood at 3.88% in 2002 but notably rose to 5.03% by 2019. During the same period, while AD prevalence decreased in the 0–1-year-old group (from 34.52% to 24.83%), it remained relatively stable in the 1–11-year-old group. Conversely, the 12–19-year-old and 20 years or older age groups witnessed substantial increases in AD prevalence, climbing from 2.55 to 6.02% and 1.44% to 3.53%, respectively. Moreover, the proportion of patients classified as having moderate to severe AD grew from 30.96 to 39.78%. Surprisingly, the prescription pattern, predominantly based on corticosteroid administration, exhibited minimal change despite the rising prevalence of moderate and severe AD cases. These findings underline a persistent reliance on corticosteroid-based treatments for AD, even as the condition's severity escalates among Korean adolescents and adults. Consequently, there is a pressing need to develop novel treatment guidelines emphasizing biologics that offer enhanced safety and efficacy.

This review article provides overall understanding of stainless, environment-friendly, and nonflammable Mg alloys (SEN alloys) recently developed at the Korea Institute of Materials Science. SEN alloys are produced by adding small amounts of Ca and Y (each

Abstract Scoliosis is a three-dimensional spinal deformity, and paraspinal muscles play an important role as stabilizers of the spinal curve. In this prospective study, we compared elasticity changes in the paraspinal muscles of adolescent patients with scoliosis after surgery or bracing. Elasticity was measured on the concave and convex sides of the paraspinal muscles at the apex of the curve at the beginning of treatment and 6 and 12 months after treatment. Twenty-six patients with correction surgery (n = 15) or bracing (n = 11) were included. At initial evaluation, the Cobb angle was larger in the surgery group (72.3 ± 20.2° in surgery vs. 30.6 ± 5.1° in brace, p

Researchers have examined the importance of school administrative support for teacher safety, victimization, anxiety, and retention; however, studies to date have rarely focused on school administrators’ perceptions of support by their district leaders, and its relation to administrators’ anxiety/stress, safety, and their intentions to transfer or quit their jobs. In the current study of 457 PreK-12th grade school administrators in the United States, structural equation modeling was used to examine relations between administrators’ perceptions of support from their district leaders and their anxiety/stress, safety, and intentions to transfer or quit their jobs. Administrator experiences of violence by student offenders served as a moderator. Results indicated that administrators’ perceptions of district leaders’ support were associated with lower intentions to transfer or quit their positions both directly and indirectly as a function of decreased anxiety/stress. District support was positively related to administrator safety, particularly for administrators who reported experiencing more student violence. Findings highlight the importance of district support of administrators for reducing mental health concerns and transfer/quit intentions in the context of student violence against school administrators. Implications of findings for research and practice are presented.

A recently developed Mg–5Bi–3Al (BA53, wt%) alloy exhibited remarkable extrudability despite its high alloying content. However, when subjected to high-speed extrusion with a die exit speed of 67 m/min, grain coarsening of recrystallized grains occurs, increasing their size from 12.1 to 26.4 μm due to excessive heat generation during extrusion. Herein, a long-range water-cooling system is installed immediately after the extrusion die to mitigate grain coarsening and attain finer grains in the high-speed extruded alloy. The results demonstrate that the use of the cooling system leads to a significant reduction in the average grain size (from 26.4 to 15.7 μm) of the BA53 alloy extruded at high speed. Furthermore, grain refinement led to notable increases in the ultimate tensile strength (from 255 to 276 MPa) and elongation (from 7.5% to 8.6%) of the alloy. These enhancements in strength and elongation are primarily attributed to the enhanced grain-boundary hardening effect and suppression of twinning during tension, both of which are consequences of grain refinement. This study underscores the effectiveness of a long-range water-cooling system, comprising water spraying over a length of 2 m, in achieving grain refinement during high-speed extrusion of the BA53 alloy and improving both the strength and ductility of the alloy after high-speed extrusion.

Abstract Osteoporosis is a state of bone weakening caused by an imbalance in osteoblast and osteoclast activity. In this study, the anti-osteoporotic effects of three proteins fermented by lactic acid bacteria (LAB) were assessed. Commercial proteins sodium caseinate (SC), whey protein isolate (WPI), and soy protein isolate (SPI) were fermented by LAB strains for 48 h. The fermented products (F-SC, F-WPI, and F-SPI, respectively) were used in an in vitro osteoclast and osteoblast-like cell model to assess their effects on bone health. Despite no difference in the results of TRAP staining of RANKL-induced osteoclastogenesis, F-WPI and F-SPI were effective in normalizing the altered gene expression of osteoclastogenesis markers such as TRAP, Nfatc1, RANK, and ATP6v0d. F-SPI was also effective in modulating osteoblasts by enhancing the expression of the osteoblastogenesis markers T1Col, Col2a, and OSX to levels higher than those in the SPI group, indicating that protein characteristics could be enhanced through bacterial fermentation. Moreover, these boosted effects of F-SPI may be involved with isoflavone-related metabolism during LAB-fermentation of SPI. These results demonstrate the potential of LAB-fermented proteins as dietary supplements to prevent bone loss. However, further understanding of its effects on balancing osteoblasts and osteoclasts and the underlying mechanisms is needed.

AbstractShiitake mushroom (Lentinula edodes) hold high nutritional and medicinal value as they contain an abundance of health-promoting compounds. However, the effect of long-term postharvest storage on the variation in the levels of health-promoting compounds has not been extensively studied. In this study, we investigated the changes in the levels of phenolic compounds, antioxidants, eritadenine, and ergothioneine in shiitake mushrooms stored at three different temperatures (1, 3, and 5 °C) for 4 weeks. Compared to mushrooms stored at lower temperatures, those stored at 5 °C exhibited a higher level of total phenolics in their pileus after 2 weeks of storage; however, storage at 5 °C also increased the deterioration of the fruiting body of these mushrooms. In mushrooms stored at all temperatures, the eritadenine content in the pilei tended to increase up to 2 weeks of storage. In contrast, the ergothioneine content in the pileus decreased during storage, with a significantly lower level detected in mushrooms stored at 5 °C for 4 weeks. Together, these results suggest that the mechanisms underlying the accumulation of phenolics and eritadenine may be related to mushroom deterioration during storage. Our findings indicate that the levels of health-promoting compounds in shiitake mushrooms are influenced by storage temperature, suggesting the potential to control adjustments of specific bioactive compounds by regulating storage conditions.

Mg–Al-based alloys with small amounts of Ca and Y, referred to as stainless, environment-friendly, nonflammable (SEN) alloys, exhibit significantly improved resistance to corrosion and ignition compared to commercial Mg alloys. This study investigates the microstructural characteristics and bending properties of extruded sheets of Mg–(9, 11)Al–1Zn–0.3Mn–0.3Ca–0.2Y alloys (SEN9 and SEN11). These sheets contain particles containing Ca or Y, such as Al2Y, Al2Ca, Al8Mn4Y, and Al–Ca–Zn phases, along with dynamically precipitated Mg17Al12 particles. In the SEN9 sheet, Mg17Al12 particles are distributed in a band-like pattern along the extrusion direction, whereas in the SEN11 sheet, a more uniform distribution of abundant Mg17Al12 particles is observed. In both sheets, a macrocrack initiates on the bottom surface of a specimen and propagates into the specimen at an angle of approximately 35° during three-point bending tests. The SEN11 sheet exhibits a higher bending yield strength (by 27%) than the SEN9 sheet, primarily due to the stronger grain-boundary and particle hardening effects in the former, resulting from finer grains and a greater number of particles. In the SEN9 sheet, sharp deformation twins and subsequent cracks along these twins are formed during bending. Meanwhile, in the SEN11 sheet, the numerous Mg17Al12 particles induce stress concentration during bending, ultimately leading to premature bending failure before the formation of twins. As a result, the SEN11 sheet exhibits a 59% lower bending formability compared to the SEN9 sheet.

A cold storage system is useful for maintaining the quality of hardy kiwifruit. However, extended cold storage periods inevitably result in cold stress, leading to lower fruit marketability; the severity of chilling injury depends on fruit types and cultivars. In this study, the impact of cold storage conditions on the physicochemical properties and antioxidant capacity of two phenotypically different hardy kiwifruit cultivars—‘Cheongsan’ (large type) and ‘Daebo’ (small type)—stored at low (L; 3 °C, relative humidity [RH]; 85–90%) and moderate-low (ML; 5 °C, RH; 85–90%) temperatures was determined. Significant differences in fruit firmness and titratable acidity between treatments L and ML were observed in both cultivars during the experimental storage period. Meanwhile, the browning and pitting rates of the ‘Cheongsan’ fruits in treatment L increased for 8 weeks compared with those of the ‘Daebo’ fruits in treatments L and ML; nonetheless, fruit decay was observed in the ‘Daebo’ fruits in treatment ML after 6 weeks. The total chlorophyll, carotenoid, flavonoid, and ascorbic acid concentrations as well as the antioxidant activities of both the cultivars significantly differed between treatments L and ML. After 2 weeks of storage, the ‘Cheongsan’ fruits in treatment L had lower antioxidant activities and ascorbic acid content than those in treatment ML. These results demonstrate that the quality attributes and antioxidant activity of hardy kiwifruit are influenced by the low-temperature storage conditions and the specific kiwifruit cultivars. Our findings suggest that optimal cold storage conditions, specific to each hardy kiwifruit cultivar, promise to maintain fruit quality, including their health-promoting compounds, during long-term storage.

Objectives. The aim of this study was to determine the most effective treatment approach by comparing the impacts of various otolith reduction techniques in patients with apogeotropic lateral semicircular canal benign paroxysmal positional vertigo (LC-BPPV). Methods. We performed a multicenter randomized prospective study from January to December 2015, involving 72 consecutive patients with apogeotropic LC-BPPV. The patients were divided into three treatment groups: therapeutic head-shaking (group A), the Gufoni-Appiani maneuver (group B), and the cupulolith repositioning maneuver (CuRM; group C). Each group underwent evaluation and treatment up to the fourth week. Treatment success was defined as the disappearance of positional vertigo and nystagmus. Results. This study included 72 patients (49 male and 23 female), with a mean (±standard deviation) age of 55.4±13.5 years. The mean duration of vertigo experienced prior to treatment was 3.9±4.4 days. The mean latency and duration of nystagmus were 2.7±3.0 seconds and 47.9±15.8 seconds, respectively. The overall treatment frequency was 2.0±0.9. The number of treatments differed significantly among the three groups (P0.05). However, CuRM was the only method with a 100% treatment success rate. Conclusion. While no clear difference was observed among the three treatments for LC-BPPV, CuRM was found to be superior to the other approaches in the long term.

This review highlights the recent advancements in Mg research in South Korea with a prime focus on high-speed-extrudable Mg–Bi-based alloys for high productivity and strength, innovative techniques utilizing {10–12} twinning for improved mechanical properties, and alloying and processing methods for enhanced corrosion resistance. High-alloyed Mg–Bi-based alloys possess thermally stable α-Mg matrix and secondary phase, which ensures high-speed extrusion of these alloys at elevated temperatures without hot cracking. Consequently, they exhibit outstanding extrudability with a maximum extrusion speed of up to 70 m/min. Furthermore, their high alloying contents offer excellent strength even after high-speed extrusion through strong solid solution hardening and particle hardening effects, making them suitable for high-performance extruded Mg products. The pre-twinning process utilizing {10–12} twinning and the combined process of pre-twinning and subsequent annealing have shown promise in controlling microstructure and texture of wrought Mg alloys and thus enhancing their mechanical properties. The pre-twinning process enhances tensile strength, fatigue properties, and age-hardening rate of Mg alloys. Furthermore, the combined processes of pre-twinning and subsequent annealing considerably improve their ductility, stretch formability, bending formability, and damping capacity. Efforts have been made to improve the corrosion resistance of Mg alloys through alloying additions, process treatments, and surface coatings. Alloying elements like Ca, Sc, and Sm alter the microstructural features (such as secondary phases and grain size) that affect the corrosion phenomenon. Process treatments such as multidirectional forging, screw rolling, and pulse electron beam can also improve the corrosion resistance by refining the microstructure. Furthermore, advanced surface coating technologies can create durable and corrosion-resistant layers for effectively protecting the Mg alloys. All these research activities conducted in South Korea have considerably contributed to the widespread utilization of Mg alloys in diverse applications by overcoming the inherent limitations of Mg alloys such as low extrudability, formability, and corrosion resistance.

This study investigates the effect of {10–12} deformation twins on the continuous precipitation behavior of an extruded Mg–8.0Al–0.5Zn–0.2Mn (AZ80) alloy during aging. The extruded AZ80 alloy is compressed along the transverse direction to introduce {10–12} twins, followed by an aging treatment at 300 °C. The extruded material exhibits a twin-free microstructure with low internal strain energy, whereas the pre-twinned material possesses abundant {10–12} twins and has high internal strain energy. The aging results reveal that the peak-aging time of the pre-twinned material (1 h) is one-eighth of that of the extruded material (8 h). Although Mg17Al12 continuous precipitates (CPs) are observed in both the peak-aged materials, these CPs are much smaller and more densely distributed in the pre-twinned material despite the significantly shorter aging time. The CPs size in the peak-aged materials increases in the following order: twinned region in the pre-twinned material (0.47 µm) < residual matrix region in the pre-twinned material (1.71 µm) < matrix region in the extruded material (2.55 µm). Moreover, the CPs number density in the twinned region of the pre-twinned material is approximately 11 times higher than that in the matrix region of the extruded material. The peak-aged pre-twinned material exhibits significantly higher tensile strength and ductility than the peak-aged extruded material. These results demonstrate that the formation of {10–12} twins in the extruded AZ80 alloy substantially accelerates the static precipitation of CPs during aging at 300 °C and improves the tensile properties of the peak-aged material.

CRISPR–Cas systems are known to be part of the bacterial adaptive immune system that provides resistance against intruders such as viruses, phages and other mobile genetic elements. To combat this bacterial defense mechanism, phages encode inhibitors called Acrs (anti-CRISPR proteins) that can suppress them. AcrIC9 is the most recently identified member of the AcrIC family that inhibits the type IC CRISPR–Cas system. Here, the crystal structure of AcrIC9 from Rhodobacter capsulatus is reported, which comprises a novel fold made of three central antiparallel β-strands surrounded by three α-helixes, a structure that has not been detected before. It is also shown that AcrIC9 can form a dimer via disulfide bonds generated by the Cys69 residue. Finally, it is revealed that AcrIC9 directly binds to the type IC cascade. Analysis and comparison of its structure with structural homologs indicate that AcrIC9 belongs to DNA-mimic Acrs that directly bind to the cascade complex and hinder the target DNA from binding to the cascade.

Abstract Extracellular vesicles (EVs) have been shown as key mediators of extracellular small RNA transport. However, carriers of cell-free messenger RNA (cf-mRNA) in human biofluids and their association with cancer remain poorly understood. Here, we performed a transcriptomic analysis of size-fractionated plasma from lung cancer, liver cancer, multiple myeloma, and healthy donors. Morphology and size distribution analysis showed the successful separation of large and medium particles from other soluble plasma protein fractions. We developed a strategy to purify and sequence ultra-low amounts of cf-mRNA from particle and protein enriched subpopulations with the implementation of RNA spike-ins to control for technical variability and to normalize for intrinsic drastic differences in cf-mRNA amount carried in each plasma fraction. We found that the majority of cf-mRNA was enriched and protected in EVs with remarkable stability in RNase-rich environments. We observed specific enrichment patterns of cancer-associated cf-mRNA in each particle and protein enriched subpopulation. The EV-enriched differentiating genes were associated with specific biological pathways, such as immune systems, liver function, and toxic substance regulation in lung cancer, liver cancer, and multiple myeloma, respectively. Our results suggest that dissecting the complexity of EV subpopulations illuminates their biological significance and offers a promising liquid biopsy approach.

A few cases of small fiber neuropathy (SFN) and tinnitus (TN) associated with coronavirus disease 2019 have been reported. However, the relationship between SFN and TN has not been studied. This study investigated a possible relationship between SFN and patients with TN (PwTNs) using autonomic function tests (AFTs) including quantitative sudomotor axon reflex tests (QSART). We performed QSARTs and other AFTs such as the Sympathetic skin response (SSR), Valsalva ratio (VR), and heart rate variability (HRV). The QSART results, obtained at seven hospitals using same protocols, were compared between PwTNs and healthy controls. We confirmed the abnormalities in SSR, VR, and HRV in PwTNs, although those parasympathetic AFTs were not performed in healthy controls. Additionally, we checked Tinnitus handicap inventory (THI) scores for PwTNs and ~50% of PwTNs had low-grade disability, whereas 9.3% had high-grade disability. Data from 57 PwTNs and 122 healthy controls were analyzed. The sweat volumes of QSART in the older age group tended to be higher in the PwTNs than in age-matched healthy controls, and significant differences between the PwTN and control groups were observed in the feet in both sexes (p < 0.001) and in the arms in women (p = 0.013). In the younger age group, the sweat volumes in the feet of men were higher in PwTNs than in healthy controls (p = 0.017). No association was observed between THI and QSART scores. In this study, the sweat volumes in QSARTs were higher in PwTNs than in healthy controls. However, abnormal SSR, HRV, and VR results were not commonly observed in PwTNs. Although the results should be interpreted with caution because of limitations in study, PwTNs might also have SFN apart from dysautonomia. This is the first study to perform QSART with other parasympathetic AFTs in PwTNs. However, larger and more rigorously controlled studies will be needed to reveal the relationship between SFN and TN in the future.

Introduction: Since 2019, the Korean government has implemented a pilot project for integrated care to encourage healthy aging of older adults. This study investigated the changes in hospitalization rates among older adults who participated in the integrated care pilot project. Methods: Administrative survey data collected from 13 local governments and the National Health Insurance Database were used in present study. The participants comprised 17,801 older adults who participated in the pilot project between August 01, 2019 and April 30, 2022 and 68,145 matched controls. A propensity score matching method was employed to select the control group, and this study employed difference-in-differences (DID) approach to examine variations in the hospitalization rate. Results: The DID analysis revealed that the odds ratio for rates of hospitalization among older adults who participated in the pilot project was 0.88 (95% confidence interval [CI] 0.84, 0.91) in comparison to control group. In specifically, as compared to the control group, the odds ratio for hospitalization rates among the pilot project’s discharged patients was 0.17 (95% CI 0.15, 0.20). Although not statistically significant, the odds ratio of older adults who utilized LTCI services was 0.93 (95% CI 0.83, 1.05), and the odds ratio of older adults who applied for LTCI but were rejected or were intensive social care was 1.09 (95% CI 0.95, 1.26) compared to the comparison group. Discussion: The findings imply that the discharged patient group had greater medical demands than the other types, and it can be claimed that this is the group that may anticipate greater efficacy while using health services. In addition, the integrated care services provided by the pilot project have the effect of reducing unnecessary hospitalization such as social hospitalization. Conclusion: Participants in the integrated care pilot project showed a lower hospitalization rate than the older adults who did not participate in the project but had similar characteristics. In particular, the admission rate of discharged patients showed a sharp decline.

Yeast, crucial in beer production, holds great potential owing to its ability to transform into a valuable by-product resource, known as brewer’s spent yeast (BSY), with potentially beneficial physiological effects. This study aimed to compare the composition and soluble polysaccharide content of Brewer’s spent yeast with those of cultured yeast strains, namely Saccharomyces cerevisiae (SC) and S. boulardii (SB), to facilitate the utilization of BSY as an alternative source of functional polysaccharides. BSY exhibited significantly higher carbohydrate content and lower crude protein content than SC and SB cells. The residues recovered through autolysis were 53.11%, 43.83%, and 44.99% for BSY, SC, and SB, respectively. Notably, the polysaccharide content of the BSY residue (641.90 μg/mg) was higher than that of SC (553.52 μg/mg) and SB (591.56 μg/mg). The yields of alkali-extracted water-soluble polysaccharides were 33.62%, 40.76%, and 42.97% for BSY, SC, and SB, respectively, with BSY comprising a comparable proportion of water-soluble saccharides made with SC and SB, including 49.31% mannan and 20.18% β-glucan. Furthermore, BSY demonstrated antioxidant activities, including superoxide dismutase (SOD), ABTS, and DPPH scavenging potential, suggesting its ability to mitigate oxidative stress. BSY also exhibited a significantly higher total phenolic compound content, indicating its potential to act as an effective functional food material.

The VITEK MS PRIME (bioMérieux, Marcy-l’Étoile, France), a newly developed matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) system, alongside the VITEK PICKME pen (PICKME), offers easy sample preparation for bacteria and yeasts. The VITEK MS PRIME also offers two software platforms for filamentous fungi: the IVD database and the RUO database. Our study evaluated its identification agreement on 320 clinical isolates of bacteria and yeasts, comparing PICKME and traditional wooden toothpick sampling techniques against MicroIDSys Elite (ASTA) results. Additionally, we assessed the IVD (v3.2) and SARAMIS (v4.16) RUO databases on 289 filamentous fungi against molecular sequencing. The concordance rates for species-level identification of bacteria and yeasts were about 89.4% (286/320) between the PICKME and wooden toothpick, and about 83.4–85.3% between the VITEK MS PRIME and ASTA MicroIDSys Elite. Retesting with PICKME improved concordance to 91.9%. For filamentous fungi, species-level identification reached 71.3% with the IVD database and 85.8% with RUO, which significantly enhanced basidiomycetes’ identification from 35.3% to 100%. Some strains in the IVD database, like Aspergillus versicolor, Exophiala xenobiotica, and Nannizzia gypsea, failed to be identified. The VITEK MS PRIME with PICKME offers reliable and efficient microorganism identification. For filamentous fungi, combined use of the RUO database can be beneficial, especially for basidiomycetes.

Key Clinical Message In this case, a patient experienced rare uterine torsion during pregnancy, detected by MRI. Diagnosis before Cesarean is helpful to achieve better outcomes, highlighting the importance of attention in high‐risk groups. Abstract Uterine torsion during pregnancy is a rare complication and its risk factors and diagnostic modalities have not yet been clearly defined. Here we present a case of uterine torsion due to unexpected pelvic adhesion. A 34‐years‐old primigravida patient underwent an emergency cesarean section for aggravated maternal preeclampsia symptoms at 34 + 0 weeks of gestation. Intraoperatively, after the baby was out, it was found that the uterus was rotated about 90 degrees to the right by dense pelvic adhesion in posterior uterine wall. In this patient, a rightward vaginal stretch was represented through a retrospective review of magnetic resonance imaging (MRI) before childbirth. To our knowledge, this is the first reported case of uterine torsion during pregnancy with MRI. Diagnosing uterine torsion in advance or paying attention to incisions during operative delivery will lead to better management in this condition and good perinatal outcomes.

BCR-ABL inhibition is an effective therapeutic approach for the treatment of chronic myeloid leukaemia (CML). Herein, we report the discovery of AKE-72 (5), a diarylamide 3-aminoindazole, as a potent pan-BCR-ABL inhibitor, including the imatinib-resistant mutant T315I. A focussed array of compounds 4a, 4b, and 5 has been designed based on our previously reported indazole I to improve its BCR-ABLT315I inhibitory activity. Replacing the morpholine moiety of I with the privileged tail (4-ethylpiperazin-1-yl)methyl afforded 5 (AKE-72) with IC50 values of < 0.5 nM, and 9 nM against BCR-ABLWT and BCR-ABLT315I, respectively. Moreover, AKE-72 potently inhibited a panel of other clinically important mutants in single-digit nanomolar IC50 values. AKE-72 elicited remarkable anti-leukemic activity against K-562 cell line (GI50 < 10 nM, TGI = 154 nM). In addition, AKE-72 strongly inhibited the proliferation of Ba/F3 cells expressing native BCR-ABL or its T315I mutant. Overall, AKE-72 may serve as a promising candidate for the treatment of CML, including those harbouring T315I mutation.

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.

A series of 6-ureido/amidocoumarins (5a–p and 7a–c) has been designed and synthesised to develop potent and isoform- selective carbonic anhydrase hCA XI and XII inhibitors. All coumarin derivatives were investigated for their CA inhibitory effect against hCA I, II, IX, and XII. Interestingly, target coumarins potently inhibited both tumour-related isoforms hCA IX (KIs: 14.7–82.4 nM) and hCA XII (KIs: 5.9–95.1 nM), whereas the cytosolic off-target hCA I and II isoforms have not inhibited by all tested coumarins up to 100 μM. These findings granted the target coumarins an excellent selectivity profile towards both hCA IX and hCA XII isoforms, supporting their development as promising anticancer candidates. Moreover, all target molecules were evaluated for their anticancer activities against HCT-116 and MCF-7 cancer cells. The 3,5-bis-trifluoromethylphenyl ureidocoumarin 5i, exerted the best anticancer activity. Overall, ureidocoumarins, particularly compound 5i, could serve as a promising prototype for the development of potent anticancer CAIs.

Background The primary aim of this study was to investigate the final adult height (FAH) of girls diagnosed with central precocious puberty (CPP) who were untreated. Methods We retrospectively analyzed the medical records of 36 girls diagnosed with CPP between 8 and 9 years of age who did not receive treatment, and 206 girls diagnosed with CPP within the same age range who received gonadotropin-releasing hormone (GnRH) agonist treatment. Midparental height (MPH), predicted adult height (PAH) obtained using height and bone age (BA) at the time of diagnosis (PAH for BA), and PAH obtained using the Bayley-Pinneau method (PAH by BP) were calculated. Additionally, height at the time of growth completion was compared with the predicted height. Results The FAHs were 160.71±4.56 cm in the untreated group and 159.31±4.26 cm in the treated group. In the untreated group, the FAH was 0.99±4.50 cm shorter than the MPH but 4.29±3.33 cm and 3.46±3.93 cm greater than the PAH for BA and PAH by BP, respectively. Conclusion In children diagnosed with CPP between 8 and 9 years of age who were untreated, FAH was greater than PAH for BA and PAH by BP at the time of diagnosis, indicating that the prognosis of FAH was not poor. Therefore, for girls diagnosed with CPP, it is recommended to consider various conditions, such as pubertal onset, height at diagnosis, BA, peak luteinizing hormone level, predicted height, and speed of puberty, when deciding whether to administer GnRH agonists.

Background : Shoulder pain is a common musculoskeletal disorder. Treatment can be surgical or non-surgical. Korean Medicine, including acupuncture and pharmacopuncture, is a part of conservative treatment. Pharmacopuncture, combining acupuncture with herbal medicine, has been used for musculoskeletal disorders since the 1960s, but clinical evidence on its effectiveness is lacking. Objectives: This study aims to assess the effectiveness and safety of pharmacopuncture for rotator cuff disease. Methods : A two-group, parallel, single-center, pragmatic, randomized, controlled, assessor-blinded trial will be conducted. A total of 40 patients will be recruited, starting in July 2022. All patients will be received acupuncture treatment, and pharmacopuncture will be applied to intervention group additionally. After eight treatments are delivered over four weeks, follow-up assessments will be performed. Results : Assessments will evaluate the effectiveness and safety of these treatments at baseline and at weeks 2 (2 W), 4 (4 W), and 8 (8 W). The primary outcome will be a visual analog scale (VAS) evaluation of shoulder pain levels. Assessments will include shoulder pain and disability index (SPADI), shoulder range of motion (ROM), EuroQol 5-Dimension 5-Level (EQ-5D-5L), patient global impression of change (PGIC), ‘no worse than mild pain’, and drug consumption rates. Conclusion : This study may offer a rationale for a future full-scale trial on the effectiveness and safety of pharmacopuncture treatment for rotator cuff disease and provide data on non-surgical treatment for the disease.

The most common type of kidney cancer in adults is renal cell carcinoma (RCC), which accounts for approximately 90% of cases. RCC is a variant disease with numerous subtypes; the most common subtype is clear cell RCC (ccRCC, 75%), followed by papillary RCC (pRCC, 10%) and chromophobe RCC (chRCC, 5%). To identify a genetic target for all subtypes, we analyzed The Cancer Genome Atlas (TCGA) databases of ccRCC, pRCC, and chromophobe RCC. Enhancer of zeste homolog 2 (EZH2), which encodes a methyltransferase, was observed to be significantly upregulated in tumors. The EZH2 inhibitor tazemetostat induced anticancer effects in RCC cells. TCGA analysis revealed that large tumor suppressor kinase 1 (LATS1), a key tumor suppressor of the Hippo pathway, was significantly downregulated in tumors; the expression of LATS1 was increased by tazemetostat. Through additional experiments, we confirmed that LATS1 plays a crucial role in EZH2 inhibition and has a negative association with EZH2. Therefore, we suggest that epigenetic control could be a novel therapeutic strategy for three subtypes of RCC.

The effects of pre-existing {10–12} extension twins on the precipitation behavior of an extruded AZ80 material during aging and on its mechanical properties after peak aging are investigated. The material containing {10–12} twins—which are formed by compression before aging (twinned material)—has a finer grain size and higher dislocation density than the extruded material. Although the peak hardnesses of the twinned and extruded materials are almost the same, the time to reach the peak hardness is considerably shorter in the former material than in the latter (4 h and 24 h, respectively). In the twinned material, the high dislocation density of the {10–12} twins promotes continuous precipitation, which results in the formation of numerous fine Mg17Al12 precipitates within the twins in the early stage of aging. The formation of these continuous precipitates reduces the driving force for discontinuous precipitation, which consequently suppresses the formation and growth of coarse Mg17Al12 precipitates at the grain boundaries. Despite its shorter peak-aging time, the 4 h-peak-aged twinned material shows higher tensile strength and elongation than the 24 h-peak-aged extruded material. These higher mechanical properties of the former material are attributed primarily to the presence of more abundant fine continuous precipitates, which are effective in strengthening the material, and less abundant coarse discontinuous precipitates, which can act as crack initiation sites. These results demonstrate that the introduction of {10–12} twins into wrought Mg–Al-based alloys can accelerate the Mg17Al12 precipitation kinetics considerably and improve the strength and ductility of the peak-aged alloys simultaneously.

Purpose: Urolithiasis is a common urinary tract disease with growing prevalence. Alpha1-adrenoceptors (α1-ARs) are abundant in ureteral smooth muscle, distributed with different α1-AR subtypes. α1D-AR is the most widely distributed in the ureter. However, the effect of α1D-AR blockade on ureteric contraction remains unknown. Materials and Methods: We dissected smooth muscle tissues (3 mm×3 mm) from the rat bladder and human ureter, tied silk strips on both tissue ends, and measured contraction in an organ bath chamber. Contraction activity in ureteral smooth muscle cells (USMCs) was immunocytochemically examined using primary rat and human USMC cultures. Results: Using the organ bath system, we determined the inhibitory effects of silodosin, tamsulosin, and naftopidil. Naftopidil significantly decreased contractility of rat bladder tissue; similar results were observed in human ureteral tissue. To confirm ex vivo experimental results in vitro , we examined the phosphorylation of myosin light chain (MLC), a marker of contractility, in a primary human USMC culture. The examined drugs decreased phospho-MLC levels in human USMCs; however, naftopidil profoundly increased MLC dephosphorylation. Conclusions: We studied the effects of naftopidil, an α1D-AR inhibitor, on the ureter. Compared with alpha-blockers, naftopidil significantly relaxed ureteral smooth muscle. Therefore, naftopidil could be an effective therapy for patients with ureteral stones.

In this study, we investigated the effect of Solanum nigrum aerial parts (SNAP) on macrophage activation and macrophage autophagy in RAW264.7 cells. SNAP increased the production of immunostimulatory factors and phagocytosis in RAW264.7 cells. TLR4 inhibition blocked SNAP-mediated production of immunostimulatory factors. In addition, the JNK inhibition reduced the SNAP-mediated production of immunostimulatory factors, and the SNAP-mediated JNK activation was blocked by the TLR4 inhibition. SNAP activated macrophage autophagy. TLR4 inhibition blocked SNAP-mediated macrophage autophagy and inhibition of p38 and JNK attenuated SNAP-mediated macrophage autophagy. These findings indicate that SNAP may induce TLR4/JNK-mediated macrophage activation and TLR4/p38 and JNK-mediated macrophage autophagy.

Under the COVID-19 pandemic, interest in immune enhancement and anti-obesity is increasing. Thus, in this study, we investigated whether Kadsura japonica fruits (KJF) exhibits immunostimulatory activity and anti-obesity activity. KJF increased the production of immunostimulatory factors and phagocytosis in RAW264.7 cells. Inhibition of TLR2 and TLR4 blocked KJF-mediated production of immunostimulatory factors in RAW264.7 cells. In addition, the inhibition of MAPK and PI3 K/AKT signaling pathway reduced KJF-mediated production of immunostimulatory factors, and the activation of MAPK and PI3 K/AKT signaling pathway by KJF suppressed the inhibition of TLR2/4. KJF attenuated the lipid accumulation and the protein expression such as CEBPα, PPARγ, perilipin-1, adiponectin, and FABP4 related to the lipid accumulation in 3T3-L1 cells. In addition, KJF inhibited excessive proliferation of 3T3-L1 cells and protein expressions such as β-catenin and cyclin D1 related to cell growth. These findings indicate that KJF may have immunostimulatory activity and anti-obesity activity.

In this study, we evaluated whether extracts of the roots of Hibiscus syriacus (HSR) exert immune activation activities and elucidated its potential mechanism in macrophages. The HSR dose-dependently increased the production of immunomodulators such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and tumor necrosis factor (TNF-α) activated phagocytosis in macrophages. Inhibition of toll-like receptors 4 (TLR4) reduced the production of immunomodulators induced by HSR. Inhibition of mitogen-activated protein kinase (MAPKs), nuclear factor-κB (NF-κB) and phosphoinositide-3 kinase (PI3K) signaling attenuated the production of immunomodulators induced by HSR. Based on the results of this study, HSR was thought to activate macrophages through the production of immunomodulators and phagocytosis activation through TLR4-dependent MAPKs, NF-κB and PI3K signaling pathways. Therefore, it is thought that the HSR has the potential to be used as agents for enhancing immunity.

Abstract Sunitinib, a VEGF blockade, is used to treat clear cell renal cell carcinoma (ccRCC). However, the anti-cancer treatment effects of sunitinib do not last long in ccRCC patients. Ginsenoside, a natural medicine extracted from ginseng, has been studied in cancer treatment and shown to have anti-tumor effects and low toxicity. We assessed cell viability and cell cycle analysis in ccRCC cell lines after treatment with ginsenoside and sunitinib. DNA damage was evaluated by measuring 8-OHdG levels and comet assay. ROS levels, reflecting the cause of oxidative stress, were also measured. Ginsenoside significantly enhanced the inhibition of cell viability by sunitinib, a result that was also confirmed in the xenograft model. In cell cycle analysis, combination treatment of ginsenoside and sunitinib enhanced G2M arrest in comparison with single-treatment groups. In addition, DNA damage was increased by ginsenoside and sunitinib according to the comet assay, and the level of 8-OHdG, which reflects oxidative DNA damage, also increased. We verified that ginsenoside enhances the efficacy of sunitinib to inhibit the proliferation of ccRCC cells via induction of oxidative DNA damage. The combination therapy of sunitinib and ginsenoside suggested the possibility of effectively treating ccRCC patients.

Immunity-related GTPase B10 (IRGB10) is a crucial member of the interferon (IFN)-inducible GTPases and plays a vital role in host defense mechanisms. Following infection, IRGB10 is induced by IFNs and functions by liberating pathogenic ligands to activate the inflammasome through direct disruption of the pathogen membrane. Despite extensive investigation into the significance of the cell-autonomous immune response, the precise molecular mechanism underlying IRGB10–mediated microbial membrane disruption remains elusive. Herein, we present two structures of different forms of IRGB10, the nucleotide-free and GppNHp-bound forms. Based on these structures, we identified that IRGB10 exists as a monomer in nucleotide-free and GTP binding states. Additionally, we identified that GTP hydrolysis is critical for dimer formation and further oligomerization of IRGB10. Building upon these observations, we propose a mechanistic model to elucidate the working mechanism of IRGB10 during pathogen membrane disruption.

Discoidin domain receptor 1 (DDR1) kinase has emerged as a promising target for cancer therapy, and selective DDR1 inhibitors have shown promise as effective therapeutic candidates. Herein, we have identified the first coumarin-based selective DDR1 inhibitors via repurposing of a recent series of carbonic anhydrase inhibitors. Among these, ureidocoumarins 3a, 3i, and 3q showed the best DDR1 inhibitory activities. The m-trifluoromethoxy phenyl member 3q potently inhibited DDR1 with an IC50 of 191 nM, while it showed less inhibitory activity against DDR2 (IC50 = 5080 nM). 3q also exhibited favorable selectivity in a screening platform with 23 common off-target kinases, including BCR-ABL. In the cellular context, 3q showed moderate antiproliferative effects, while 3i, with the third rank in DDR1 inhibition, exerted the best anticancer activity with sub-micromolar GI50 values over certain DDR1-dependent cell lines. Molecular docking and MD simulations disclosed the putative binding mode of this coumarin chemotype and provided insights for further optimization of this scaffold. The present findings collectively supported the potential improvement of ureidocoumarins 3i and 3q for cancer treatment.

Plastome sequences are crucial in plant studies due to their role in examining genomic evolution, understanding phylogenetic relationships, and developing molecular markers. Despite the collection of information about Korean figs, their genomic data remain underexplored. We utilize next-generation sequencing and PCR techniques to investigate genomic data and to develop and validate molecular markers. In this study, we characterize the complete plastomes of Korean figs: F. erecta, F. erecta var. sieboldii, F. sarmentosa var. nipponica, and F. sarmentosa var. thunbergii, which range in length from 160,276 to 160,603 bp. These genomes comprise 78 plastid protein-coding genes, 30 tRNA, and four rRNA, with the exception of one pseudogene, infA. We discovered that F. erecta and F. erecta var. sieboldii share identical plastome sequences. Phylogenomic analysis indicates the monophyly of Ficus, although the relationships among its subgenera remain unclear. We discovered that Ficus possesses 467 molecular diagnostic characters in its plastid protein-coding genes compared to other Moraceae groups, and F. erecta exhibits 33 molecular diagnostic characters. Single nucleotide polymorphisms in ndhD, petA, and rbcL were effectively used to develop molecular markers for distinguishing F. erecta from other figs. Additionally, we provided a straightforward PCR protocol for utilizing these newly developed molecular markers.