Overactive bladder (OAB) is characterized by urinary urgency and increased urinary frequency, and can impact quality of life significantly. Tamsulosin and mirabegron combination therapy has been studied as a safe and effective treatment option for patients with OAB. This study evaluated the effects of combining these two drugs on their pharmacokinetics and safety profiles in healthy Korean males. In this open-label, fixed-sequence, 3-period, drug-drug interaction phase 1 study, a total of 36 male participants were administered multiple doses of tamsulosin alone (0.2 mg once daily), mirabegron alone (50 mg once daily), and a combination of both drugs. The results showed that the combination of tamsulosin and mirabegron increased tamsulosin exposure in the plasma by approximately 40%. In contrast, the maximum plasma concentration of mirabegron reduced by approximately 17%, when administered along with tamsulosin. No clinically significant changes in safety profiles, vital signs, or clinical laboratory test results were observed in this study. In conclusion, there were no clinically relevant drug-drug interactions between tamsulosin and mirabegron in terms of pharmacokinetics, safety, and tolerability, suggesting that their combination therapy could be a promising treatment option for patients with OAB.

Tomato is exposure to diverse abiotic stresses. Cold stress is one of harsh environmental stresses and abnormal low temperature affects tomato growth and development including physio- logical disorders, flower drops, and abnormal fruit morphology, causing the decrease of tomato yield and a fruit quality. It is important to identify low temperature-(LT) tolerant tomato (Solanum lycopersicum L.) cultivars relying on different fruit types. This study focused on analyzing physiological traits of 35 tomato accessions with three different fruit types (cherry, medium, and large sizes) under night temperature set-points of 15°C for normal temperature (NT) and 10°C for LT, respectively. Plant heights (PH) of most tomato accessions in LT were remarkably decreased compared to those in NT. The growth of leaf length (LL) and leaf width (LW) was reduced depending on the genotypes under LT. In addition, the number of fruits (NFR), fruit set (FS), fruit yield (FY), and marketable yield (MY) were negatively affected in LT. The variation was further investigated by the correlation analysis, the principal component (PCA), and the cluster analysis. Interestingly, positive correlations between different vegetative and reproductive traits were uncovered. Multivariate analysis including the PCA and hierarchical clustering classified LT-treated 35 tomato accessions into four major groups. The identified accessions were associated with vegetative and reproductive parameters on positive directions and might be utilized for breeding programs on selecting LT-tolerant cultivars.

Chilling injury (CI), which causes seed browning in pepper, may arise following long-term cold storage, and is a major cause of postharvest losses. To explore potential strategies of minimizing the associated postharvest losses, the present study investigated the optimal pepper harvest time that could reduce levels of seed browning, in addition to the relationship between fruit maturity and seed browning. Fruit harvested 15 days after flowering (DAF) were sensitive to cold storage at 4°C and exhibited 100% seed browning (CI index, 4.0); in contrast, the seed browning rate of fruit harvested 35 DAF was 10% (CI index, 0.4) within 7 d of cold storage. Seed antioxidant activity was higher in seeds harvested at early stages (15 DAF to 20 DAF) than in seeds harvested at later stages (40 DAF to 50 DAF) at the beginning of storage. Pericarps of fruit harvested at 50 DAF exhibited the highest antioxidant activity. Lipoxygenase, catalase, and peroxidase activity, and the expression levels of cell wall-related genes, pectin methylesterase-like protein, and endo-β-1,4-glucanase were higher in seeds of immature fruit harvested 15 DAF than in seeds of mature fruit harvested 35 DAF. The endosperm separated from the seed coat in fruit harvested 35 DAF and the seeds did not brown under low-temperature storage. The lack of seed browning observed in mature fruit under low-temperature storage could be attributed to physical protection provided by the seed coat rather than cold stress resistance conferred by antioxidants.

Low night temperature (LNT) can be a practical and economical target in tomato breeding programs in terms of energy saving in greenhouses. This study was conducted to investigate the physiological responses to LNT using four tomato accessions of cherry and large fruit types with LNT tolerance and sensitivity grown in two greenhouses with night temperature set-points of 10 and 15°C for heating. LNT significantly reduced plant height regardless of fruit types and LNT tolerance. The number of flowers were significantly reduced in 10°C in cherry but not in large fruit types. Fruit set in 10°C was significantly lower in LNT sensitive accessions than tolerant ones regardless of fruit types, which was due to abnormal flower morphology in 10°C. Proline accumulation patterns between 10 and 15°C significantly differed between fruit types as well as between LNT tolerant and sensitive accessions. Chlorophyll content in 10 °C was significantly higher at later growth stages in LNT tolerant accessions than sensitive ones in both fruit types. No clear difference in photosynthetic parameters was observed between fruit types or tolerance and sensitive accessions except for photosynthetic rate, which was significantly lower in tolerant than sensitive accessions during early growing period. These results suggest that different tomato fruit types may have different mechanisms for LNT tolerance.

Fexuprazan is a potassium-competitive acid blocker approved for treating gastric acid-related diseases. Herein, we evaluated the pharmacokinetics (PKs) of single-dose and multiple-dose oral administration of fexuprazan 10 mg tablets in healthy subjects (Part 1) and investigated the bioequivalence between fexuprazan 10 mg and 40 mg tablets (Part 2). Part 1 comprised a single- and multiple-dose, 1-sequence, and 2-period design, and Part 2 comprised a single-dose, 2×2 crossover design. Eight and 23 subjects completed Parts 1 and 2, respectively. In Part 1, multiple doses accumulated twice as much as single doses. In Part 2, the geometric mean ratios [90% confidence intervals] for maximum plasma concentration (Cmax) and area under the concentration–time curve from zero to the time of the last quantifiable concentration (AUClast) of four fexuprazan 10 mg tablets to those of one fexuprazan 40 mg tablet were 1.0290 (0.9352–1.1321) and 1.0290 (0.9476–1.1174), respectively, which met bioequivalence criteria. Overall, favorable PK was observed after single and multiple administrations of one fexuprazan 10 mg tablet, and four fexuprazan 10 mg tablets were pharmacokinetically equivalent to one fexuprazan 40 mg tablet.

(1) Background: The aim of the present study was to evaluate the effect of ETS homologous factor (EHF) in malignant breast cancer cells. (2) Methods: Overexpression and knockdown of the EHF gene in human and mouse breast cancer cells were performed, and the TCGA dataset and Q-omics were analyzed. (3) Results: We found that the tumor suppressor NDRG2 is correlated with EHF gene expression in triple-negative breast cancer cells, that EHF overexpression results in reduced cell proliferation and that apoptosis is promoted by chemotherapeutic reagent treatment of EHF-overexpressing cells. By EHF overexpression, senescence-associated β-galactosidase activity and p21WAF1/CIP1 expression were increased, suggesting that EHF may induce cellular senescence. In addition, overexpression of EHF reduced the migratory ability and inhibited epithelial-mesenchymal transition (EMT). Furthermore, EHF inhibited the phosphorylation of STAT3. Overexpression of EHF also reduced tumor size, and lung metastasis in vivo. At the tumor site, β-galactosidase activity was increased by EHF. Finally, Kaplan-Meier-plotter analysis showed that TNBC patients with high expression of EHF had a longer relapse-free survival rate. (4) Conclusions: Our findings demonstrated that EHF inhibits breast tumor progression by inducing senescence and regulating EMT in TNBC cells.

Pepper plants experience complex environmental factors including abiotic and biotic stresses in field and the importance of climate changes including low and high temperatures has been emerged. Low temperature stress in the growth and development is one of the most critical issues, which directly impact on the crop yield and productivity of pepper plants. It is essential to select and breed low temperature-(LT) tolerant pepper (Capsicum annuum L.) cultivars. The research was performed to assess the agronomical traits of 39 pepper accessions belonging to chili and bell fruit types which cultivated two different night temperature set-points at 15°C for suboptimal temperature (CT) and at 10°C for low temperature (LT), respectively. Plant heights (PH) of most pepper accessions in LT were significantly decreased compared to those in CT. The stem diameter (SD) and the length of main axis (LMA) were various depending on the genotypes under LT. Moreover, the number of flowers (NFL), the total number of fruits (NFR), fruit yield (FY), fruit fresh weight (FFW), fruit length (FL), fruit diameter (FD), and the number of seeds in a fruit (NSF) were notably declined in LT compared to CT. The evaluated agronomical traits between LT and CT were further applied for the correlation analysis, the principal component analysis (PCA), and the hierarchical cluster analysis. Notably, FY trait was correlated with other reproductive traits including NFR, FFW, FD, and FL on positive directions and LT treated-39 pepper accessions were clustered into seven groups by the clustering analysis. The selected accessions were primarily involved with the positive trends with the reproductive index including NFR, FL, FD, and FW traits and would be used for pepper breeding programs on developing LT-tolerant cultivars.

Understanding the mechanism for heat tolerance is important for the hot pepper breeding program to develop heat-tolerant cultivars in changing climate. This study was conducted to investigate physiological and biochemical parameters related to heat tolerance and to determine leaf heat damage levels critical for selecting heat-tolerant genotypes. Seedlings of two commercial cultivars, heat-tolerant ‘NW Bigarim’ (NB) and susceptible ‘Chyung Yang’ (CY), were grown in 42 °C for ten days. Photosynthesis, electrolyte conductivity, proline content were measured among seedlings during heat treatment. Photosynthetic rate was significantly reduced in ‘CY’ but not in ‘NB’ seedlings in 42 °C. Stomatal conductivity and transpiration rate was significantly higher in ‘NB’ than ‘CY’. Proline content was also significantly higher in ‘NB’. After heat treatment, leaf heat damages were determined as 0, 25, 50 and 75% and plants with different leaf heat damages were moved to a glasshouse (30–32/22–24 °C in day/night). The growth and developmental parameters were investigated until 70 days. ‘NB’ was significantly affected by leaf heat damages only in fruit yield while ‘CY’ was in fruit set, number and yield. ‘NB’ showed fast recovery after heat stress compared to ‘CY’. These results suggest that constant photosynthetic rate via increased transpiration rate as well as high proline content in heat stress condition confer faster recovery from heat damage of heat-tolerant cultivars in seedlings stages.

High temperature (HT) significantly affects the crop physiological traits and reduces the 12 productivity in plants. To increase yields as well as survival of crops under HT, developing heat13 tolerant plants is one of the main targets in crop breeding programs. The present study attempted 14 to investigate the linkage of the heat tolerance between the seedling and the reproductive growth 15 stages of tomato cultivars ’Dafnis‘ and ’Minichal’. This research was undertaken to evaluate heat 16 tolerance under two experimental designs such as screening at seedling stage and screening from 17 reproductive traits in greenhouses. Survival rate and physiological responses in seedlings of 18 tomatoes with 4-5 true leaf were estimated under HT (40 °C, RH 70%, day/night, respectively) and 19 under two control and HT greenhouse conditions (day time 28 °C and 40 °C, respectively). Heat 20 stress significantly affected physiological-chemical (photosynthesis, electrolyte conductivity, 21 proline) and vegetative parameters (plant height, shoot fresh weight, root fresh weight) in all 22 tomatoes seedlings. The finding revealed that regardless of tomato cultivars the photosynthesis, 23 chlorophyll, total proline and electrical conductivity parameters were varied in seedlings during the 24 heat stress period. The heat tolerance rate of tomatoes in the seedling stage might not be associated 25 always with reproductive parameters. HT reduced the fruit parameters likeas fruit weight (31.9%), 26 fruit length (14.1%), fruit diameter (19.1%) and fruit hardness (9.1%) in compared to NT under HT 27 in heat susceptible tomato cultivar ‘Dafnis’, while in heat tolerant cultivar ‘Minichal’ fruit length 28 (7.1%) and fruit diameter (12.1%) was decreased by the affect of HT but on the contrary fruit weight 29 (3.6%) and fruit hardness (8.3%) were increased. In conclusion, screening and selection for tomatoes 30 should be evaluated at the vegetative and reproductive stages with consideration of reproductive 31 parameters.