unal level.After parturition, cows frequently develop uterine bacterial infections, resulting in the onset of endometritis. To eliminate the bacteria, bovine endometrial cells secrete chemokines, such as IL-6 and MCP1, which attract macrophages (MΦs) to the subepithelial stroma. These attracted MΦs are not only involved in bacterial elimination but also the orchestration of inflammation and tissue repair. These immune responses aid in the recovery from endometritis; however, the recovery from endometritis takes longer in summer than in any other season. Based on these findings, we hypothesized that heat stress (HS) affects the chemokine production in endometrial cells. To confirm this hypothesis, we compared IL-6 and MCP1 production induced by lipopolysaccharide (LPS) in bovine endometrial epithelial and stromal cells under normal (38.5°C) and HS conditions (40.5°C). In the endometrial epithelial cells, IL-6 production stimulated by LPS was significantly (p less then .05) suppressed under HS conditions. MCP1 production in endometrial epithelial cells was not detected under both the control and HS conditions regardless of the presence of LPS. Moreover, LPS significantly (p less then .05) stimulated IL-6 and MCP1 production in endometrial stromal cells. Moreover, HS significantly (p less then .05) enhanced their production compared to that under the control conditions. In addition, HS did not affect the migration ability of MΦs; however, the supernatant of the endometrial stromal cells cultured under the HS condition significantly (p less then .05) attracted the MΦs when compared to the control condition. These results suggest that HS disrupts chemokine production in two types of endometrial cells and alters the distribution of MΦs in the endometrium during the summer.High-altitude pulmonary hypertension (HAPH) is a severe and progressive disease caused by chronic hypoxia and subsequent pulmonary vascular remodeling. No cure is currently available owing to an incomplete understanding about vascular remodeling. It is believed that hypoxia-induced diseases can be prevented by treating hypoxia. Thus, this study aimed to determine whether daily short-duration reoxygenation at sea level attenuates pulmonary hypertension under high-altitude hypoxia. To this end, a simulated 5000-m hypoxia rat model and hypoxic cultured human pulmonary artery smooth muscle cells were used to evaluate the effect of short-duration reoxygenation.  https://www.selleckchem.com/products/cinchocaine.html  Results show that intermittent, not continuous, short-duration reoxygenation effectively attenuates hypoxia-induced pulmonary hypertension. The mechanisms underlining the protective effects involved that intermittent, short-duration reoxygenation prevented functional and structural remodeling of pulmonary arteries and proliferation, migration, and phenotypic conversion of pulmonary artery smooth muscle cells under hypoxia. The specific genes or potential molecular pathways responsible for mediating the protective effects were also characterised by RNA sequencing. Further, the frequency and the total time of intermittent reoxygenation affected its preventive effect of HAPH, which was likely attributable to augmented oxidative stress. Hence, daily intermittent, not continuous, short-duration reoxygenation partially prevented pulmonary hypertension induced by 5000-m hypoxia in rats. This study is novel in revealing a new potential method in preventing HAPH. It gives insights into the selection and optimisation of oxygen supply schemes in high-altitude areas.Frequencies of circulating T follicular helper (cTfh) functional subsets vary in autoimmune diseases. We evaluated the frequencies and clinical relevance of functional subsets of cTfhs in patients with different degrees of stenosis. Blood samples were collected from high (≥50%) (n = 12) and low ( less then 50%) stenosis (n = 12) groups and healthy controls (n = 6). Three subsets of cTfh cells including cTfh1 (CXCR3+ CCR6- ), cTfh2 (CXCR3- CCX6- ), and cTfh17 (CXCR3- CCR6+ ) were detected by flow cytometry. The frequency of cTfh1 cells was higher in control (p = .0006) and low-stenosis groups (p = .005) compared to high-stenosis group. The percentages of cTfh2 and cTfh17 cells were increased in high-stenosis compared to low-stenosis (p = .002 and p = .007) and control groups (p = .0004 and p = .0005), respectively. The frequency of cTfh1 cells negatively correlated with cholesterol (p = .040; r = -.44), C-reactive protein (CRP) (p = .015; r = -.68), erythrocyte sedimentation rate (ESR) (p = .002; r = -.79), neutrophil/lymphocyte ratio (NLR) (p = .028; r = -.67), and cTfh17 (p = .017; r = -.7244) in the high-stenosis group. The percentages of cTfh2 and cTfh17 cells positively correlated with cholesterol (p = .025; r = .77 and p = .033; r = .71), CRP (p = .030; r = .61 and p = .020; r = .73), ESR (p = .027; r = .69 and p = .029; r = .70), NLR (p = .004; r = .76 and p = .005; r = .74), and with each other (p = .022; r = .7382), respectively, in the high-stenosis group. The increased frequencies of cTfh2 and cTfh17 subsets and their correlation with laboratory parameters in patients with atherosclerosis may suggest their role in promoting the inflammatory response and atherosclerosis progression.The l-type amino acid transporter 1 (LAT1, SLC7A5) imports dietary amino acids and amino acid drugs (e. g., l-DOPA) into the brain, and plays a role in cancer metabolism. Though there have been numerous reports of LAT1-targeted amino acid-drug conjugates (prodrugs), identifying the structural determinants to enhance substrate activity has been challenging. In this work, we investigated the position and orientation of a carbonyl group in linking hydrophobic moieties including the anti-inflammatory drug ketoprofen to l-tyrosine and l-phenylalanine. We found that esters of meta-carboxyl l-phenylalanine had better LAT1 transport rates than the corresponding acylated l-tyrosine analogues. However, as the size of the hydrophobic moiety increased, we observed a decrease in LAT1 transport rate with a concomitant increase in potency of inhibition. Our results have important implications for designing amino acid prodrugs that target LAT1 at the blood-brain barrier or on cancer cells.