Background: Postmenopausal Osteoporosis (PMOP) is characterized by decreased bone mass and deterioration of bone microarchitecture, leading to increased fracture risk. Current treatments often have adverse effects, necessitating safer alternatives. Kaempferol, a flavonoid identified as a key active component of the traditional Chinese medicine Yishen Gushu formula, has shown promise in improving bone health, but its mechanisms in PMOP treatment remain unclear. Objective: The aim of this study was to investigate the therapeutic effects and underlying mechanisms of kaempferol in the treatment of PMOP. Methods: A bilateral ovariectomized (OVX) rat model was established to simulate PMOP. Sixty female Sprague-Dawley rats were divided into six groups: Sham operation, OVX control, OVX with alendronate (ALN), and OVX with kaempferol at doses of 10, 20, and 40 mg/kg. Treatments were administered orally once daily for 12 weeks. Assessments included Bone Mineral Density (BMD), trabecular microarchitecture via histopathology, organ morphology, organ indices, and serum levels of bone metabolism markers (TRACP-5b, BALP, ALP, Ca, P, and Fe) as well as liver and kidney function indicators (ALT, AST, CREA, and urea). Tandem Mass Tag (TMT) quantitative proteomics and bioinformatics analyses were conducted on femur samples to identify differentially expressed proteins (DEPs). Key DEPs were validated using parallel reaction monitoring (PRM), immunohistochemistry, and molecular docking. Results: Kaempferol significantly improved BMD and enhanced trabecular microarchitecture in OVX rats in a dose-dependent manner, comparable to ALN, without causing hepatic, renal, or estrogen- like side effects. Serum bone metabolism markers were normalized with kaempferol treatment. Proteomic analysis identified 902 DEPs associated with kaempferol treatment, involved in processes such as bone remodeling, skeletal system development, and osteoclast function. Key signaling pathways affected included NF-κB, PI3K-AKT, and HIF-1. Notably, kaempferol downregulated five key DEPs—Rac2, Ddb1, Cdc42, Rpl19, and Hist2h4-in the femur, which are crucial for osteoclast resorptive activity, migration, adhesion, and cell cycle progression. Conclusion: Kaempferol exerts therapeutic effects on PMOP by inhibiting key proteins involved in osteoclast function, thereby reducing bone resorption and promoting bone health. These findings suggested that kaempferol is a potential safer alternative for PMOP treatment. Further research is recommended to explore its clinical applications and elucidate detailed mechanisms. conclusion: Kaempferol may reduce osteoclast resorptive activity, migration, adhesion ability, and polarization level, increase apoptosis, and slow the cell cycle of osteoclasts by inhibiting Hist2h4, Cdc42, and Rac2 protein expression, thus exerting an anti-PMOP effect. other: None.
Alfalfa is an important forage and have been planted for more than 2000 years in China.Carrying a lot of genetic variation,alfalfa is an excellent plant for genetic diversity research,but the breeding rate and level of research of alfalfa is behind of other crops.In the research of the genetic diversity of alfalfa germplasm by using molecular markers,a good PCR amplification system is essential.The orthogonal design was used to optimize SRAP-PCR amplification system on Medicago varia Martin at four levels of five factors(Taq DNA polymerase,Mg2+,DNA template,dNTP and primer)respectively.This optimized system for SRAP marker would become one of the effective protocols for further research.The different factors have a significant impact on the PCR reaction.The quantity of dNTP was the most important affected factor of PCR,and the concentration of template DNA had the minimal impact.Various factors and their changes in the level had the impact on PCR reaction,in which descending order is dNTP,Taq DNA polymerase,Mg2+,primer and DNA template.One of the most suitable 25 μL SRAP-PCR systems for Medicago varia Martin.containing dNTP 2 μL(0.20 mmol·L-1),Taq DNA polymerase 0.3 μL(1.50 U),Mg2+ 3 μL(1.50 mmol·L-1),each primer 1 μL(0.40 μmol·L-1),50 ng DNA template 1 μL and 10×PCR buffer 2.5 μL(exclusion Mg2+) was established.This optimized SRAP-PCR system would play an important role in Medicago map construction,genetic diversity analysis,germplasm identification and so on.
The correlation between cuff inflatable hypertension and the difference in interarm diastolic pressure induced by single arm ischemia is investigated. A total of 126 patients undergoing coronary angiography in our hospital from January 2020 to January 2021 are selected and divided into the non-pseudohypertension (non-PHT) group (64 cases) and the PHT group (62 cases) according to the difference between systolic blood pressure and diastolic blood pressure measured directly and indirectly. The patients are subjected to the beam arm ischemia test and blood pressure measurement. The diastolic pressure differences between the patients before and after the beam arm are analyzed, and endothelial function and imaging indicators are compared. The risk factors for PHT are analyzed by binary logistic regression, and the diagnostic efficacy of diastolic blood pressure difference interarms (DBPI-r) for PHT patients is analyzed by receiver operating characteristic (ROC) curve. The experimental results show that the diastolic pressure difference induced by single arm ischemia can be used in the diagnosis of cuff inflatable hypertension.
In this paper, we propose an image-space contrast enhancement method for color-encoded visualization. The contrast of an image is enhanced through a perceptually-guided approach that interfaces with the user with a single and intuitive parameter of the virtual viewing distance. To this end, we analyze a multiscale contrast model of the input image and test the visibility of bandpass images of all scales at a virtual viewing distance. By adapting weights of bandpass images with a threshold model of spatial vision, this image-based method enhances contrast to compensate for contrast loss caused by viewing the image at a certain distance. Relevant features in the color image can be further emphasized by the user using overcompensation. The method is efficient and can be integrated into any visualization tool as it is a generic image-based post-processing technique. Using highly diverse datasets, we show the usefulness of perception compensation across a wide range of typical visualizations.
<p>PDF file - 1275K, Supplemental Table 1. Synergism between MK-8776 and SBHA or vorinostat in various human leukemia cell lines. Supplemental Figure S1. SBHA or vorinostat significantly potentiates lethality of MK-8776 in leukemia cell lines. Supplemental Figure S2. SBHA or vorinostat enhances Chk1 inhibition by MK-8776. Supplemental Figure S3. Disruption of Chk1 function increases S phase population and sensitizes cells to SBHA or vorinostat, in association with Cdt1 downregulation. Supplemental Figure S4. MK-8776/HDACIs abrogate intra-S-phase checkpoint and induce DNA damage in association with disruption of the CtIP/BRCA1 pathway that mediates DNA repair via HR. Supplemental Figure S5. Knock-down of p53 by shRNA sensitizes in p53-wt leukemia cells to the MK-8776/SBHA regimen, and this regimen is active against leukemia CD34+/CD38-/CD123+ primitive population. Supplemental Figure S6. The MK-8776/HDACI regimen is active against primary AML cells, while spare normal CD34+ cells.</p>
To develop and validate a model for predicting death risk in septic shock patients using LASSO-Logistic methods.A retrospective cohort study was conducted. Based on the open-source database Medical Information Mart for Intensive Care-III v1.4 (MIMIC-III v1.4), the septic shock patients meeting the Sepsis-3 criteria were included, and the data on demographic characteristics, major signs, laboratory examinations, hospitalization, and outcomes were extracted. Predictive variables were selected by LASSO regression and predictive models were derived using Logistic regression. The calibration of the model was evaluated using the Hosmer-Lemeshow test and discrimination was evaluated using the receiver operator characteristic curve (ROC curve).A total of 693 patients with septic shock were enrolled, in which 445 patients survived and 248 patients dead within 30 days and the mortality was 35.8%. Logistic regression model was constructed according to nine predictive variables and outcome variables screened by LASSO regression method, which showed that advanced age, Elixhauser index, blood lactic acid (Lac), K+ level and mechanical ventilation were associated with increased 30-day mortality [odds ratio (OR) and 95% confidence interval (95%CI) was 1.023 (1.010-1.037), 1.047 (1.022-1.074), 1.213 (1.133-1.305), 2.241 (1.664-3.057), 2.165 (1.433-3.301), respectively, all P < 0.01], and reduced systolic blood pressure (SBP), diastolic blood pressure (DBP), body temperature, and pulse oxygen saturation (SpO2) were also associated with increased 30-day mortality [OR (95%CI) was 0.974 (0.957-0.990), 0.972 (0.950-0.994), 0.693 (0.556-0.857), 0.971 (0.949-0.992), respectively, all P < 0.05]. The calibration curve showed that the predicted risk of septic shock death risk prediction model had good agreement with the real situation. ROC curve analysis showed that the area under the ROC curve (AUC) of the prediction model was 0.839 (95%CI was 0.803-0.876), which could distinguish patients at risk of death from those at risk of survival.The septic shock death risk prediction model has a good ability to identify the 30-day mortality risk of septic shock patients, including nine hospital readily variables (age, Elixhauser index, mechanical ventilation, Lac, K+, SBP, DBP, body temperature and SpO2). The model could be used by clinicians to calculate the risk of death in septic shock individuals.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
