AGAMOUS-LIKE 24 (AGL24) is a key gene regulating floral transition, but its involvement in flower organ identity remains largely unknown. In this study, we found that RhAGL24 is strongly related to petal and stamen development in rose. Its expression increases rapidly at the petal primordium development stage and maintains a high level until the complete differentiation stage. RhAGL24 silencing increases the number of malformed petals and decreases the number of stamens, indicating that this gene affects stamen petaloidy. RhAG (AGAMOUS), a class C gene associated with petal and stamen development, is downregulated in RhAGL24-silenced plants. Moreover, we found that RhAGL24 could directly bind to the promoter region of RhARF18 (AUXIN RESPONSE FACTORS 18), a regulator of RhAG. Our results suggested that RhAGL24-RhARF18 module regulates stamen petaloidy in rose and provide new insights into the function of AGL24 for plants.
Aloperine is a quinolizidine alkaloid extracted from the leaves of Sophora plants. It has been recognized with the potential to treat inflammatory and allergic diseases as well as tumors. In this report, we demonstrate that pretreatment with aloperine provided protection for mice against ischemia-reperfusion (IR)-induced acute renal injury as manifested by the attenuated inflammatory infiltration, reduced tubular apoptosis, and well-preserved renal function. Mechanistic studies revealed that aloperine selectively repressed IL-1β and IFN-γ expression by regulating PI3K/Akt/mTOR signaling and NF-κB transcriptional activity. However, aloperine did not show a perceptible impact on IL-6 and TGF-β expression and the related Jak2/Stat3 signaling. It was also noted that aloperine regulates AP-1 activity, through which it not only enhances SOD expression to increase reactive oxygen species (ROS) detoxification but also promotes the expression of antiapoptotic Bcl-2, thereby preventing tubular cells from IR-induced apoptosis. Collectively, our data suggest that administration of aloperine prior to IR insults, such as renal transplantation, could be a viable approach to prevent IR-induced injuries.
Abstract Kdm2a catalyzes H3K36me2 demethylation to play an intriguing epigenetic regulatory role in cell proliferation, differentiation, and apoptosis. Herein we found that myeloid-specific knockout of Kdm2a ( LysM- Cre- Kdm2a f/f , Kdm2a −/− ) promoted macrophage M2 program by reprograming metabolic homeostasis through enhancing fatty acid uptake and lipolysis. Kdm2a −/− increased H3K36me2 levels at the Pparg locus along with augmented chromatin accessibility and Stat6 recruitment, which rendered macrophages with preferential M2 polarization. Therefore, the Kdm2a −/− mice were highly protected from high-fat diet (HFD)-induced obesity, insulin resistance, and hepatic steatosis, and featured by the reduced accumulation of adipose tissue macrophages and repressed chronic inflammation following HFD challenge. Particularly, Kdm2a −/− macrophages provided a microenvironment in favor of thermogenesis. Upon HFD or cold challenge, the Kdm2a −/− mice manifested higher capacity for inducing adipose browning and beiging to promote energy expenditure. Collectively, our findings demonstrate the importance of Kdm2a-mediated H3K36 demethylation in orchestrating macrophage polarization, providing novel insight that targeting Kdm2a in macrophages could be a viable therapeutic approach against obesity and insulin resistance.
Malnutrition, mainly caused by inadequate energy intake, predicts poor prognostic outcome in chronic kidney disease (CKD) patients. In this study, we aim to explore the effect of non-protein energy supplement in CKD stage 3b-5 (CKD3b-5) malnourished patients with or without receiving continuous peritoneal dialysis (PD).30 patients with CKD3b-5 and 20 patients who received PD were identified as malnourished according to Subjective Global Assessment (SGA), and enrolled into this clinical study. Compared with the control group which just received regular nutrition counseling, an additional non-protein energy supplement (600 kcal) was given to the participants for 12 weeks in the intervention group. Before and after study, the nutritional status of patients was judged by human body composition measurement, anthropometric parameters, physical fitness test, and quality of life survey. Other biochemical indexes relating to nutrition, renal function and inflammatory response were also included for disease evaluation.After 12 weeks of oral non-protein energy supplementation, the body weight, body fat and associated anthropometric parameters significantly increased upon intervention. Also, the participants showed enhanced physical fitness and better life quality in the intervention group. Consistently, the improved nutritional status was further confirmed by biochemical examinations. However, we did not observe a perceptible change of renal function, measured residual renal function, or general inflammatory response indices after intervention.12 weeks of oral non-protein energy supplement could efficiently improve the nutritional status of CKD3b-5 patients and those who receive peritoneal dialysis; meanwhile, it has little effect on renal function and inflammatory response.
Melatonin (N-acetyl-5-methoxytryptamine), a circadian-regulating hormone, has been reported to exert a protective role during acute kidney injury (AKI) induced by renal ischemia-reperfusion injury (I/R). High-mobility group box 1 (HMGB1) is a novel member of the damage-associated molecular pattern (DAMP) family, and has been verified to be an inflammatory cytokine mediating AKI induced by I/R and cisplatin. However, the effect of melatonin on HMGB1, as well as the relationship of these two with folic acid induced AKI are elusive. In this study, we sought to identify the role of melatonin on folic acid induced AKI and its association with HMGB1. Pretreatment with melatonin significantly attenuated folic acid-induced increase in serum creatinine and BUN levels, renal tubular epithelial cell (TEC) apoptosis, and the infiltration of inflammatory cells and secretion of cytokines. Moreover, melatonin pretreatment promoted renal tubular proliferation and improved cell cycle arrest of TECs after folic acid-induced renal damage. This protective role of melatonin was closely related to the inhibition of nucleocytoplasmic translocation of HMGB1 in TECs. These data provide a strong proof that administering melatonin prior to folic acid insult may shed light on a potential treatment for AKI.
Intramural pregnancy is a rare ectopic pregnancy in which the gestational sac is implanted between the muscle walls. Due to the lack of specific clinical manifestations, it is easy to misdiagnose or miss them. If it is allowed to get worse, the uterus will burst, and there will be a lot of bleeding in the later stages, which could lead to the death of the patient.The patient had no history of uterine surgery, embryo transplantation, or any other operations. She complained of having abdominal distention and swelling of the waist but no vaginal bleeding or lower abdomen discomfort.According to her transvaginal ultrasonography, we highly suspected ectopic pregnancy. Hysteroscopy combined with laparoscopy is an effective treatment option that can prevent life-threatening problems. During the surgery, pituitrin helped find the gestational sac, and the pathology report confirmed that it was an intramural pregnancy.Hysteroscopy combined with laparoscopy is an effective treatment option that can prevent life-threatening problems. During the surgery, we used pituitrin to help find the gestational sac. The use of pituitrin can minimize bleeding during a uterine operation and indicate the location of an intramural pregnancy, helping surgeons to complete the operation successfully.The patient recovered quickly and was discharged on the 4th day after surgery, with a significant decrease in human chorionic gonadotrophin (HCG) levels from 14,792.26 mIU/mL before surgery to 1071.40 mIU/mL at discharge. During the follow up, her HCG level dropped to 50.90 mIU/mL on the 14th day after the surgery. She monitored the HCG levels intermittently until they fell within the normal range.Intramural pregnancy is a rare form of ectopic pregnancy, and it is difficult to diagnose early on. This may result in uterine rupture or even life-threatening hemorrhage. If an intramural pregnancy is suspected in early pregnancy, hysteroscopy combined with laparoscopy is advised, and if necessary, low-dose posterior pituitary hormone can enhance uterine contractions and better reveal the position of the gestational sac within the uterine wall.
Most of the current crop row detection algorithms focus on extracting crop canopy rows as location information. However, for some high-pole crops, due to the transverse deviation of the position of the canopy and roots, the agricultural machinery can easily cause the wheel to crush the crop when it is automatically driven. In fact, it is more accurate to use the crop root row as the feature for its location calibration, so a method of crop root row detection is proposed in this paper. Firstly, the ROI (region of interest) of the crop canopy is extracted by a semantic segmentation algorithm, then crop canopy row detection lines are extracted by the horizontal strip division and the midpoint clustering method within the ROI. Next, the Crop Root Representation Learning Model learns the Representation of the crop canopy row and crop root row to obtain the Alignment Equation. Finally, the crop canopy row detection lines are modified according to the Alignment Equation parameters to obtain crop root row detection lines. The average processing time of a single frame image (960 × 540 pix) is 30.49 ms, and the accuracy is 97.1%. The research has important guiding significance for the intelligent navigation, tilling, and fertilization operation of agricultural machinery.
The functional state of T cells is diverse and under dynamic control for adapting to the changes of microenvironment. Reversible protein phosphorylation represents an important post-translational modification that not only involves in the immediate early response of T cells, but also affects their functionality in the long run. Perturbation of global phosphorylation profile and/or phosphorylation of specific signaling nodes result in aberrant T cell activity. Dual specific phosphatases (DUSPs), which target MAPKs and beyond, have increasingly been emerged as a versatile regulator in T cell biology. Herein in this mini review, we sought to summarize and discuss the impact of DUSP proteins on the regulation of effector T cell activity, T cell polarization, regulatory T cell development and T cell senescence/exhaustion. Given the distinctive engagement of each DUSP member under various disease settings such as chronic infection, autoimmune disorders, cancer and age-related diseases, DUSP proteins likely hold the promise to become a druggable target other than the existing therapeutics that are predominantly by manipulating protein kinase activity.
Saccharomyces boulardii ( S. boulardii ) is a probiotic yeast that is widely used to treat gastrointestinal disorders. The present study is aimed to explore the therapeutic effects of S. boulardii on dextran sulfate sodium‐ (DSS‐) induced murine ulcerative colitis (UC) and illustrate the mechanisms of action. C57BL/6 mice were administered S. boulardii (10 5 and 10 7 CFU/ml, p.o. ) for 3 weeks and then given DSS [2.5% ( w / v )] for one week. Administration of S. boulardii prevented DSS‐induced reduction in body weight, diarrhea, bloody feces, decreased colon length, and loss of histological structure. Moreover, S. boulardii protected the intestinal barrier by increasing the levels of tight junction proteins zona occludens‐1 and Occludin and exerted immunomodulatory effects in DSS‐induced mice. Furthermore, S. boulardii suppressed the colonic inflammation by reducing the levels of Interleukin‐1 β , Interleukin‐6, and Tumor necrosis factor alpha and restored myeloperoxidase activity in mice exposed to DSS. S. boulardii also mitigated colonic oxidative damage by increasing the levels of antioxidant enzymes (superoxide dismutase, catalase, and heme oxygenase 1) and glutathione and decreasing malondialdehyde accumulation. Further studies identified that S. boulardii suppressed the nuclear translocation of nuclear factor kappa B (NF‐ κ B) p65 subunit by decreasing I κ K α / β levels, while promoted the nuclear translocation of nuclear factor erythroid 2‐related factor 2 (Nrf2) in DSS‐exposed mice. Collectively, S. boulardii possessed an appreciable therapeutic effect against the experimental mice model of UC. The protective mechanism of S. boulardii may involve inhibition of NF‐ κ B‐mediated proinflammatory signaling and activation of Nrf2‐modulated antioxidant defense in addition to intestinal barrier protective and immunomodulatory effects.
Abstract Purpose Patients with end stage renal disease (ESRD) lose the capacity of renal potassium excretion and often suffer from persistent hyperkalemia, especially for those requiring maintenance hemodialysis (HD). Sodium zirconium cyclosilicate (SZC) is the most recently approved K + binding agent in China. It is reported SZC is an effective and well-tolerated treatment for pre-dialysis hyperkalemia in patients with ESRD undergoing adequate hemodialysis. We thus conducted a retrospective study to compare the therapeutic efficiency of SZC and sodium polystyrene sulfonate (SPS, another classic K + binding agent) on hyperkalemia in HD patients. Methods: 38 patients with persistent pre-dialysis hyperkalemia were included, and 18 patients were treated by SZC while 20 patients were treated by SPS. The changes of serum potassium level were followed up for 7 months. Results: We observed that the potassium reducing capacity of SZC and SPS were comparable at the first 3 months, but SZC displayed better long-term therapeutic effect. Conclusion: Our results supported that SZC is a good option for treatment of hard-controlled pre-dialysis hyperkalemia.