Exploring the dietary and therapeutic potential of licorice (Glycyrrhiza uralensis Fisch.) sprouts.

ETHNOPHARMACOLOGICAL RELEVANCE: This research substantiates the traditional use of Glycyrrhiza uralensis Fisch. for liver health, with scientific evidence of the non-toxic and lipid-lowering properties of licorice sprout extracts. The sprouts' rich mineral and amino acid content, along with their strong antioxidant activity, reinforce their value in traditional medicine. These findings bridge ancient herbal practices with modern science, highlighting licorice's potential in contemporary therapeutic applications. AIM OF THE STUDY: The study aimed to investigate the dietary and medicinal potential of G. uralensis sprouts by assessing their safety, nutritional content, and antioxidant properties using both plant and animal models. Specifically, the study sought to determine the effects of different sizes of licorice sprouts on lipid metabolism in human liver cancer cells and their overall impact on rat health indicators. MATERIALS AND METHODS: The study examined the effects of aqueous and organic extracts from G. uralensis sprouts of varying lengths on the cytotoxicity, lipid metabolism, and antioxidant activity in HepG2 cells, alongside in vivo impacts on Sprague-Dawley rats, using MTT, ICP, and HPLC. It aimed to assess the potential health benefits of licorice sprouts by analyzing their protective effects against oxidative stress and their nutritional content. RESULTS: Licorice sprout extracts from G. uralensis demonstrated no cytotoxicity in HepG2 cells, significantly reduced lipid levels, and enhanced antioxidant activities, with the longest sprouts (7 cm) showing higher mineral, sugar, and arginine content as well as increased glycyrrhizin and liquiritigenin. In vivo studies with Sprague-Dawley rats revealed weight gain and improved antioxidant enzyme activities in blood plasma and liver tissues after consuming the extracts, highlighting the sprouts' dietary and therapeutic potential. CONCLUSIONS: This study is the first to demonstrate that G. uralensis sprouts, particularly those 7 cm in length, have no cytotoxic effects, reduce lipids, and have high mineral and antioxidant contents, offering promising dietary and therapeutic benefits.

Vincristine Enhances the Efficacy of MEK Inhibitors in Preclinical Models of KRAS-mutant Colorectal Cancer.

Mutations in KRAS are found in more than 50% of tumors from patients with metastatic colorectal cancer (mCRC). However, direct targeting of most KRAS mutations is difficult; even the recently developed KRASG12C inhibitors failed to show significant benefit in patients with mCRC. Single agents targeting mitogen-activated protein kinase kinase (MEK), a downstream mediator of RAS, have also been ineffective in colorectal cancer. To identify drugs that can enhance the efficacy of MEK inhibitors, we performed unbiased high-throughput screening using colorectal cancer spheroids. We used trametinib as the anchor drug and examined combinations of trametinib with the NCI-approved Oncology Library version 5. The initial screen, and following focused validation screens, identified vincristine as being strongly synergistic with trametinib. In vitro, the combination strongly inhibited cell growth, reduced clonogenic survival, and enhanced apoptosis compared with monotherapies in multiple KRAS-mutant colorectal cancer cell lines. Furthermore, this combination significantly inhibited tumor growth, reduced cell proliferation, and increased apoptosis in multiple KRAS-mutant patient-derived xenograft mouse models. In vivo studies using drug doses that reflect clinically achievable doses demonstrated that the combination was well tolerated by mice. We further determined that the mechanism underlying the synergistic effect of the combination was due to enhanced intracellular accumulation of vincristine associated with MEK inhibition. The combination also significantly decreased p-mTOR levels in vitro, indicating that it inhibits both RAS-RAF-MEK and PI3K-AKT-mTOR survival pathways. Our data thus provide strong evidence that the combination of trametinib and vincristine represents a novel therapeutic option to be studied in clinical trials for patients with KRAS-mutant mCRC. SIGNIFICANCE: Our unbiased preclinical studies have identified vincristine as an effective combination partner for the MEK inhibitor trametinib and provide a novel therapeutic option to be studied in patients with KRAS-mutant colorectal cancer.

Effects of spectral variability due to sediment and bottom characteristics on remote sensing for suspended sediment in shallow rivers.

Advances in remote sensing techniques for water environments have led to acquisition of abundant data on suspended sediment concentration (SSC). However, confounding factors, such as particle sizes, mineral properties, and bottom materials, have not been fully studied, despite their substantial interference with the detection of intrinsic signals of suspended sediments. Therefore, we investigated the spectral variability arising from the sediment and bottom using laboratory and field-scale experiments. In the laboratory experiment, we focused on measuring spectral characteristics of suspended sediment according to particle size and sediment type. The laboratory experiment was conducted under conditions of completely mixed sediment and non-bottom reflectance using a specially designed rotating horizontal cylinder. To investigate the effects of different channel bottoms under sediment-laden flow conditions, we performed sediment tracer tests in field-scale channels comprising sand and vegetated bottoms. Based on experimental datasets, we performed spectral analysis and multiple endmember spectral mixture analysis (MESMA) to quantify the effect of spectral variability of sediment and bottom on the relationship between hyperspectral data and SSC. The results showed that optimal spectral bands were precisely estimated under non-bottom reflectance conditions, and the effective wavelengths depended on the sediment type. The fine sediments had a higher backscattering intensity compared to the coarse sediments, and the reflectance difference according to the particle size difference increased as the SSC increased. However, in the field-scale experiment, the bottom reflectance substantially decreased the R2 in the relationship between the hyperspectral data and SSC. Nevertheless, MESMA can quantify the contribution of suspended sediment and bottom signals as fractional images. Moreover, the suspended sediment fraction had a clear exponential relationship with SSC in all cases. We conclude that MESMA-driven sediment fractions could be an important alternative for estimating SSC in shallow rivers, as it quantifies the contributions of each factor and then minimizes the bottom effect.

Research Progress in the Field of Microbial Mitigation of Drought Stress in Plants.

Plants defend themselves against ecological stresses including drought. Therefore, they adopt various strategies to cope with stress, such as seepage and drought tolerance mechanisms, which allow plant development under drought conditions. There is evidence that microbes play a role in plant drought tolerance. In this study, we presented a review of the literature describing the initiation of drought tolerance mediated by plant inoculation with fungi, bacteria, viruses, and several bacterial elements, as well as the plant transduction pathways identified via archetypal functional or morphological annotations and contemporary "omics" technologies. Overall, microbial associations play a potential role in mediating plant protection responses to drought, which is an important factor for agricultural manufacturing systems that are affected by fluctuating climate.

Combined inhibition of HMGCoA reductase and mitochondrial complex I induces tumor regression of BRAF inhibitor-resistant melanomas.

BACKGROUND: Primary and posttreatment resistance to BRAFV600 mutation-targeting inhibitors leads to disease relapse in a majority of melanoma patients. In many instances, this resistance is promoted by upregulation of mitochondrial oxidative phosphorylation (OxPhos) in melanoma cells. We recently showed that a novel electron transport chain (ETC) complex I inhibitor, IACS-010759 (IACS), abolished OxPhos and significantly inhibited tumor growth of high-OxPhos, BRAF inhibitor (BRAFi)-resistant human melanomas. However, the inhibition was not uniform across different high OxPhos melanomas, and combination with BRAFi did not improve efficacy. METHODS: We performed a high-throughput unbiased combinatorial drug screen of clinically relevant small molecules to identify the most potent combination agent with IACS for inhibiting the growth of high-OxPhos, BRAFi-resistant melanomas. We performed bioenergetics and carbon-13 metabolite tracing to delineate the metabolic basis of sensitization of melanomas to the combination treatment. We performed xenograft tumor growth studies and Reverse-Phase Protein Array (RPPA)-based functional proteomics analysis of tumors from mice fed with regular or high-fat diet to evaluate in vivo molecular basis of sensitization to the combination treatment. RESULTS: A combinatorial drug screen and subsequent validation studies identified Atorvastatin (STN), a hydroxymethylglutaryl-coenzyme A reductase inhibitor (HMGCRi), as the most potent treatment combination with IACS to inhibit in vitro cell growth and induce tumor regression or stasis of some BRAFi-resistant melanomas. Bioenergetics analysis revealed a dependence on fatty acid metabolism in melanomas that responded to the combination treatment. RPPA analysis and carbon-13 tracing analysis in these melanoma cells showed that IACS treatment decreased metabolic fuel utilization for fatty acid metabolism, but increased substrate availability for activation of the mevalonate pathway by HMGCR, creating a dependence on this pathway. Functional proteomic analysis showed that IACS treatment inhibited MAPK but activated AKT pathway. Combination treatment with STN counteracted AKT activation. CONCLUSIONS: STN and other clinically approved HMGCRi could be promising combinatorial agents for improving the efficacy of ETC inhibitors like IACS in BRAFi-resistant melanomas.

Quality Characteristics and Antioxidant Potential of Lemon (Citrus limon Burm. f.) Seed Oil Extracted by Different Methods.

Lemon (Citrus limon Burm. f.) is one of the most widely produced and consumed fruits in the world. The seeds of lemon are generally discarded as waste. The purpose of this study was to investigate the quality characteristics and antioxidant potential of lemon seed oil obtained by four extraction methods (roasted-pressing at 170°C, RP-170; roasted-pressing at 100°C, RP-100; cold-pressing, CP; and supercritical fluid, SF). No significant differences in the viscosity, density, and refractive index were observed in the oil obtained from different methods. In the case of Hunter's value, L (lightness) and b (yellowness) values of SF were higher than those of the others. The oil obtained by the CP method exhibited higher levels of Ca (252.17 mg/kg), Cu (2.38 mg/kg), K (225.98 mg/kg), and Mo (0.47 mg/kg) than that of other methods. The highest contents of total phenols (165.90 mg/mL) and flavonoids (21.69 mg/mL) were significantly high in oil obtained by the SF method. Oleic and linoleic acids consisted of principal fatty acids, which were significantly higher in oil obtained by RP-170. Higher amounts of volatile flavor compounds, such as γ-terpinene, sabinene, and limonene, were observed in CP compared to those observed for the other methods. This study elucidates the effects of different methods of oil extraction on the composition of lemon seed oil and highlights potential applications of these benefits in the food, cosmetic, pharmaceutical, and/or fragrance industries.

Therapeutically actionable signaling node to rescue AURKA driven loss of primary cilia in VHL-deficient cells.

Loss of primary cilia in cells deficient for the tumor suppressor von Hippel Lindau (VHL) arise from elevated Aurora Kinase A (AURKA) levels. VHL in its role as an E3 ubiquitin ligase targets AURKA for degradation and in the absence of VHL, high levels of AURKA result in destabilization of the primary cilium. We identified NVP-BEZ235, a dual PI3K/AKT and mTOR inhibitor, in an image-based high throughput screen, as a small molecule that restored primary cilia in VHL-deficient cells. We identified the ability of AKT to modulate AURKA expression at the transcript and protein level. Independent modulation of AKT and mTOR signaling decreased AURKA expression in cells confirming AURKA as a new signaling node downstream of the PI3K cascade. Corroborating these data, a genetic knockdown of AKT in cells deficient for VHL rescued the ability of these cells to ciliate. Finally, inhibition of AKT/mTOR using NVP-BEZ235 was efficacious in reducing tumor burden in a 786-0 xenograft model of renal cell carcinoma. These data highlight a previously unappreciated signaling node downstream of the AKT/mTOR pathway via AURKA that can be targeted in VHL-null cells to restore ciliogenesis.

Identification of the Antidepressant Function of the Edible Mushroom Pleurotus eryngii.

Pleurotus eryngii produces various functional molecules that mediate physiological functions in humans. Recently, we observed that P. eryngii produces molecules that have antidepressant functions. An ethanol extract of the fruiting body of P. eryngii was obtained, and the extract was purified by XAD-16 resin using an open column system. The ethanol eluate was separated by HPLC, and the fraction with an antidepressant function was identified. Using LC-MS, the molecular structure of the HPLC fraction with antidepressant function was identified as that of tryptamine, a functional molecule that is a tryptophan derivative. The antidepressant effect was identified from the ethanol extract, XAD-16 column eluate, and HPLC fraction by a serotonin receptor binding assay and a cell-based binding assay. Furthermore, a forced swimming test (FST) showed that the mice treated with purified fractions of P. eryngii exhibited decreased immobility time compared with nontreated mice. From these results, we suggest that the extract of P. eryngii has an antidepressant function and that it may be employed as an antidepressant health supplement.

The Role of Zinc in Copper Homeostasis of Aspergillus fumigatus.

Copper is an essential metal ion that performs many physiological functions in living organisms. Deletion of Afmac1, which is a copper-responsive transcriptional activator in A. fumigatus, results in a growth defect on aspergillus minimal medium (AMM). Interestingly, we found that zinc starvation suppressed the growth defect of the Δafmac1 strain on AMM. In addition, the growth defect of the Δafmac1 strain was recovered by copper supplementation or introduction of the CtrC gene into the Δafmac1 strain. However, chelation of copper by addition of BCS to AMM failed to recover the growth defect of the Δafmac1 strain. Through Northern blot analysis, we found that zinc starvation upregulated CtrC and CtrA2, which encode membrane copper transporters. Interestingly, we found that the conserved ZafA binding motif 5'-CAA(G)GGT-3' was present in the upstream region of CtrC and CtrA2 and that mutation of the binding motif led to failure of ZafA binding to the upstream region of CtrC and upregulation of CtrC expression under zinc starvation. Furthermore, the binding activity of ZafA to the upstream region of CtrC was inversely proportional to the zinc concentration, and copper inhibited the binding of ZafA to the upstream region of CtrC under a low zinc concentration. Taken together, these results suggest that ZafA upregulates copper metabolism by binding to the ZafA binding motif in the CtrC promoter region under low zinc concentration, thus regulating copper homeostasis. Furthermore, we found that copper and zinc interact in cells to maintain metal homeostasis.

Response to the letter 'Absent regulation of iron acquisition by the copper regulator Mac1 in A. fumigatus'.

The answer to the letter 'Absent regulation of iron acquisition by the copper regulator Mac1 in A. fumigatus' has been prepared. We explained our data and showed supplementary information to answer the questions. And we respect the results of other groups first and explain the differences from our results.

Yield and quality characteristics of Korean red bean sprouts produced with different time of seed soaking.

This study was conducted to investigate the yield and quality characteristics of red bean sprouts of three cultivars (Arari, Geomguseul, and Chungju) soaked in water for 0, 6, 12 or 24 h. The sprout yields of 'Arari' and 'Geomguseul' on day 7 were highest with the seeds soaked for 12 h. For 'Chungju', the yields from the seeds soaked for 12 and 24 h were not significantly (p > 0.05) different. Longer hypocotyls and shorter roots, which are also desirable characteristics of good sprouts, were also found in the sprouts with 12 h of seed soaking. The amounts of total minerals, thiamine, total free amino acids, and total phenols and DPPH radical scavenging potential of sprouts of all cultivars were higher than those of their seeds. This study showed that higher yield and better quality of red bean sprouts could be obtained with the seeds soaked for 12 h.

The Role of Zinc in Gliotoxin Biosynthesis of Aspergillus fumigatus.

Zinc performs diverse physiological functions, and virtually all living organisms require zinc as an essential trace element. To identify the detailed function of zinc in fungal pathogenicity, we carried out cDNA microarray analysis using the model system of Aspergillus fumigatus, a fungal pathogen. From microarray analysis, we found that the genes involved in gliotoxin biosynthesis were upregulated when zinc was depleted, and the microarray data were confirmed by northern blot analysis. In particular, zinc deficiency upregulated the expression of GliZ, which encodes a Zn2-Cys6 binuclear transcription factor that regulates the expression of the genes required for gliotoxin biosynthesis. The production of gliotoxin was decreased in a manner inversely proportional to the zinc concentration, and the same result was investigated in the absence of ZafA, which is a zinc-dependent transcription activator. Interestingly, we found two conserved ZafA-binding motifs, 5'-CAAGGT-3', in the upstream region of GliZ on the genome and discovered that deletion of the ZafA-binding motifs resulted in loss of ZafA-binding activity; gliotoxin production was decreased dramatically, as demonstrated with a GliZ deletion mutant. Furthermore, mutation of the ZafA-binding motifs resulted in an increase in the conidial killing activity of human macrophage and neutrophil cells, and virulence was decreased in a murine model. Finally, transcriptomic analysis revealed that the expression of ZafA and GliZ was upregulated during phagocytosis by macrophages. Taken together, these results suggest that zinc plays an important role in the pathogenicity of A. fumigatus by regulating gliotoxin production during the phagocytosis pathway to overcome the host defense system.

Dealcoholization of Korean traditional rice wine, takju, combining thermal, bentonite clarification or reverse osmosis treatment.

The objective of this study was to prepare low-alcoholic takju. Low-alcohol (3.06%) and dealcoholized (0.04-0.28%) takju samples were prepared by adopting bentonite clarification, heat and reverse osmosis treatments. The dealcoholization of takju, in most cases, significantly (p < 0.05) reduced the total mineral (from 505.80 to 258.61 mg/L), free amino acid (from 989.81 to 293.58 mg/mL), antioxidant potentials and total phenolic (from 345.30 to 156.30 µg GAE/mL) contents remained in the control to RO-3 (takju sample obtained from 3-time reverse osmosis and heat treatment). Similarly, the content of volatile compounds was also significantly (p < 0.05) decreased with the dealcoholization treatments. The finding of this study clearly showed that dealcoholized takju could be prepared but at the expense of reduced nutritional and antioxidant potentials. This study could be an exemplary in promoting traditional beverages in different countries by producing low or alcohol-free drinks.

Bexarotene - a novel modulator of AURKA and the primary cilium in VHL-deficient cells.

Loss of the gene von Hippel-Lindau (VHL) is associated with loss of primary cilia and is causally linked to elevated levels of Aurora kinase A (AURKA). We developed an image-based high-throughput screening (HTS) assay using a dual-labeling image analysis strategy that identifies both the cilium and the basal body. By using this strategy, we screened small-molecule compounds for the targeted rescue of cilia defects associated with VHL deficiency with high accuracy and reproducibility. Bexarotene was identified and validated as a positive regulator of the primary cilium. Importantly, the inability of an alternative retinoid X receptor (RXR) agonist to rescue ciliogenesis, in contrast to bexarotene, suggested that multiple bexarotene-driven mechanisms were responsible for the rescue. We found that bexarotene decreased AURKA expression in VHL-deficient cells, thereby restoring the ability of these cells to ciliate in the absence of VHL Finally, bexarotene treatment reduced the propensity of subcutaneous lesions to develop into tumors in a mouse xenograft model of renal cell carcinoma (RCC), with a concomitant decrease in activated AURKA, highlighting the potential of bexarotene treatment as an intervention strategy in the clinic to manage renal cystogenesis associated with VHL deficiency and elevated AURKA expression.

Effects of the bottom slope and guiding wall length on the performance of a vortex drop inlet.

Laboratory experiments were conducted to assess the performance of a vortex drop inlet with a spiral intake in subcritical and supercritical flow conditions. The water surface elevation at multiple locations was measured for different flowrates by varying the extent of the guiding wall and the longitudinal and radial bottom slopes. The measurements show that a steeper longitudinal bottom slope decreases the water surface elevation at the beginning of the intake, resulting in a transcritical flow in the intake structure. However, a steeper longitudinal bottom slope also causes the maximum water surface elevation to occur within the spiral intake. For an effective vortex drop inlet design, achieving a low water surface elevation throughout the entire spiral intake structure is required. Experimental results show that the two seemingly conflicting design criteria, namely, achieving a low water surface elevation in the approach channel and reducing the maximum water surface elevation in the intake structure, can be simultaneously achieved by adding a radial bottom slope.

Switchable electrorheological activity of polyacrylonitrile microspheres by thermal treatment: from negative to positive.

The study focuses on the effect of thermal deformation degree of polyacrylonitrile (PAN) particles on the electrorheological (ER) properties of their suspensions. The heat-treated PAN particles are manufactured as ER materials using a thermocatalytic processes. The molecular structures of ER materials are analyzed to confirm a stabilization or a carbonization degree. We categorized the prepared ER particles into three basic types according to their deformation degree: Thermal dried PAN, stabilized PAN, and pre-carbonized PAN. The raw, stabilized, and pre-carbonized PAN particle-dispersed suspensions showed positive ER properties. The ER properties are enhanced as the heat-treatment temperature increases due to improved dielectric property. However, the thermal dried PAN particle ER suspensions showed negative ER behavior though the particles have higher conductivity and dielectric constants than those of the host fluid, which is contrary to the conduction model. XRD results indicate that the ER materials could show contradictory ER behavior even if they have the same molecular structures due to their crystallinity. This discovery is expected to boost the development of both positive ER and negative ER suspensions based on carbonaceous ER materials.

A copper transcription factor, AfMac1, regulates both iron and copper homeostasis in the opportunistic fungal pathogen Aspergillus fumigatus.

Although iron and copper are co-ordinately regulated in living cells, the homeostatic effects of each of these metals on the other remain unknown. Here, we show the function of AfMac1, a transcriptional activator of the copper and iron regulons of Aspergillus fumigatus, on the interaction between iron and copper. In addition to the copper-specific AfMac1-binding motif 5'-TGTGCTCA-3' found in the promoter region of ctrC, the iron-specific AfMac1-binding motif 5'-AT(C/G)NN(A/T)T(A/C)-3' was identified in the iron regulon but not in the copper regulon by ChIP sequence analysis. Furthermore, mutation of the AfMac1-binding motif of sit1 eliminated AfMac1-mediated sit1 up-regulation. Interestingly, the regulation of gene expression in the iron regulon by AfMac1 was not affected by copper and vice versa AfMac1 localized to the nucleus under iron- or copper-depleted conditions, and AfMac1 was mostly detected in the cytoplasm under iron- or copper-replete conditions. Taken together, these results suggest that A. fumigatus independently regulates iron and copper homeostasis in a manner that involves AfMac1 and mutual interactions.

Comparison of acetabular and femoral morphologies on hip, pelvic, and lumbar radiographs.

PURPOSE: To evaluate the reliability of the parameters for acetabular/femoral pathomorphologies in L-spine and hip radiographs compared to pelvic radiographs. METHODS: A retrospective review of L-spine, hip, and pelvic radiographs from 101 patients was performed. Three radiologists independently measured five parameters (acetabular roof angle of Tönnis [Tönnis angle], center-edge-angle of Wiberg [CEA], femoral head extrusion index [FHEI], cross-over sign, pistol-grip deformity) in each radiograph. RESULTS: No significant differences were identified (p ≥ 0.07) except Tönnis angles and FHEIs from the L-spine radiographs. Inter-radiograph/inter-reader ICCs were excellent or good. CONCLUSION: Pathomorphology-related measurements in L-spine radiographs can also be used as alternatives to those in pelvic or hip radiographs. If L-spine radiographs are already available, additional pelvic or hip radiographs may be unnecessary, thus reducing patients' overall radiation exposure.

Diagnostic accuracy of low-dose versus ultra-low-dose CT for lumbar disc disease and facet joint osteoarthritis in patients with low back pain with MRI correlation.

OBJECTIVE: To compare the image quality, radiation dose, and diagnostic performance between low-dose (LD) and ultra-low-dose (ULD) lumbar-spine (L-spine) CT with iterative reconstruction (IR) for patients with chronic low back pain (LBP). METHODS: In total, 260 patients with chronic LBP who underwent L-spine CT between November 2015 and September 2016 were prospectively enrolled. Of these, 143 underwent LD-CT with IR and 117 underwent ULD-CT with IR. The patients were divided according to their body mass index (BMI) into BMI1 (<22.9 kg/m2), BMI2 (23.0-24.9 kg/m2), and BMI3 (≥25 kg/m2) groups. Two blinded radiologists independently evaluated the signal-to-noise ratio (SNR), qualitative image quality, and final diagnoses (lumbar disc disease and facet joint osteoarthritis). L-spine MRIs interpreted by consensus were used as the reference standard. All data were statistically analyzed. RESULTS: ULD protocol showed significantly lower SNR for all patients (p < 0.001) except the vertebral bodies and lower qualitative image quality for BMI3 patients (p ≤ 0.033). There was no statistically significant difference between ULD (sensitivity, 95.1-98.1%; specificity, 92.5-98.7%; accuracy, 94.6-98.0%) and LD protocols (sensitivity, 95.6-100%; specificity, 95.5-98.9%; accuracy, 97.4-98.1%), (all p≥0.1) in the BMI1 and BMI2; while dose was 60-68% lower with the ULD protocol. Interobserver agreements were excellent or good with regard to image quality and final diagnoses. CONCLUSIONS: For the BM1 and BMI2 groups, ULD-CT provided an acceptable image quality and exhibited a diagnostic accuracy similar to that of LD-CT. These findings suggest that it is a useful diagnostic tool for patients with chronic LBP who exhibit a BMI of <25 kg/m2.