The effect of PDK1 in maintaining immune cell development and function.

3-phosphoinositide-dependent protein kinase 1 (PDK1) exhibits a substantial influence on immune cell development by establishing a vital connection between PI3K and downstream mTOR signaling cascades. However, it remains unclear whether PDK1 signaling affects the homeostasis and functionality of immune cells. To explore the impact of PDK1 on different immune cells within immune organs, transgenic mouse strains with lymphocyte-specific PDK1 knockout (PDK1fl/fl CD2-Cre) were generated. Unlike wild-type (WT) mice, lymphocyte-specific PDK1 knockout (KO) mice exhibited thymic atrophy, elevated percentages of CD8+ T cells and neutrophils, and reduced proportions of γδ T cells, B cells, and NK cells in the spleen. Functional analysis revealed elevated release of IFN-γ and IL-17A by T cells in PDK1 KO mice, contrasting with diminished levels observed in γδ T cells and Treg cells. Furthermore, the activation, cytotoxicity, and migratory potential of γδ T cells in PDK1 KO mice are heightened, indicating a potential association with the regulation of the mTOR signaling pathway. To conclude, the findings of this research demonstrated that specific knockout of PDK1 in lymphocytes hindered T cell development in the thymus and exhibited a substantial influence on immune cell homeostasis in the spleen and lymph nodes.

Precise Topographic Model Assisted Slope Displacement Retrieval from Small Baseline Subsets Results: Case Study over a High and Steep Mining Slope.

Due to the intrinsic side-looking geometry of synthetic aperture radar (SAR), time series interferometric SAR is only able to monitor displacements in line-of-sight (LOS) direction, which limits the accuracy of displacement measurement in landslide monitoring. This is because the LOS displacement is only a three dimensional projection of real displacement of a certain ground object. Targeting at this problem, a precise digital elevation model (DEM) assisted slope displacement retrieval method is proposed and applied to a case study over the high and steep slope of the Dagushan open pit mine. In the case study, the precise DEM generated by laser scanning is first used to minimize topographic residuals in small baseline subsets analysis. Then, the LOS displacements are converted to slope direction with assistance of the precise DEM. By comparing with ground measurements, relative root mean square errors (RMSE) of the estimated slope displacements reach approximately 12-13% for the ascending orbit, and 5.4-9.2% for the descending orbit in our study area. In order to validate the experimental results, comparison with microseism monitoring results is also conducted. Moreover, both results have found that the largest slope displacements occur on the slope part, with elevations varying from -138 m to -210 m, which corresponds to the landslide area. Moreover, there is a certain correlation with precipitation, as revealed by the displacement time series. The outcome of this article shows that rock mass structure, lithology, and precipitation are main factors affecting the stability of high and steep mining slopes.

High-level expression, purification and characterisation of porcine ß-defensin 2 in Pichia pastoris and its potential as a cost-efficient growth promoter in porcine feed.

Porcine ß-defensin 2 (pBD2), a recently discovered porcine defensin that is produced by the intestine, exerts antimicrobial activities and innate immune effects that are linked to intestinal diseases in pigs. Here, we report a codon-optimised protein corresponding to mature pBD2 cDNA that was expressed and purified in Pichia pastoris yeast. The highest amount of secreted protein (3,694.0 mg/L) was reached 144 h into a 150-h induction during high-density cultivation. Precipitation followed by gel exclusion chromatography yielded 383.7 mg/L purified recombinant pBD2 (rpBD2) with a purity of ~93.7 %. Two recombinant proteins of 5,458.5 and 5,258.4 Da were detected in the mass spectrum due to variation in the amino-terminus. The rpBD2 exhibited high antimicrobial activity against a broad range of pig pathogenic bacteria (minimal inhibitory concentration [MIC] 32-128 µg/mL); the highest activity was observed against Salmonella choleraesuis, Staphylococcus aureus and Streptococcus suis (MIC 32-64 µg/mL). However, rpBD2 also inhibited the growth of probiotics such as Lactobacillus plantarum, Bacillus subtilis and Saccharomyces cerevisiae, but at lower efficacies than the pathogens. Purified or unpurified rpBD2 also maintained high activity over a wide range of pH values (2.0-10.0), a high thermal stability at 100 °C for 40 min and significant resistance to papain, pepsin and trypsin. In addition, the activity of rpBD2 towards S. aureus was unaffected by 10 mM dithiothreitol (DTT) and 20 % dimethyl sulphoxide (DMSO). Our results suggest that pBD2 could be produced efficiently in large quantities in P. pastoris and be a substitute for traditional antibiotics for growth promotion in the porcine industry.

Clinical Characteristics and Prognostic Predictors of Pneumocystis Jirovecii Pneumonia in Patients with and without Chronic Pulmonary Disease: A Retrospective Cohort Study.

Objective: Pneumocystis jirovecii pneumonia (PJP) is a severe respiratory infection caused by Pneumocystis jirovecii in immunocompromised hosts. The role of P. jirovecii colonization in the development or progression of various pulmonary diseases has been reported. Our aim was to explore serial change in serum biomarkers and the independent risk factors for mortality in patients with and without chronic pulmonary diseases who developed PJP. Methods: We performed a retrospective study to select patients with Pneumocystis jirovecii pneumonia between January 1, 2012, and December 31, 2021. Information regarding demographics, clinical characteristics, underlying diseases, laboratory tests, treatment, and outcomes was collected. Univariate and multivariate logistic regression analyses were used to identify independent predictors of in-hospital mortality. Results: A total of 167 patients diagnosed with PJP were included in the study: 53 in the CPD-PJP group and 114 in the NCPD-PJP group. The number of patients with PJP showed an increasing trend over the 10-year period. A similar trend was observed for in-hospital mortality. Independent risk factors associated with death in the NCPD-PJP group were procalcitonin level (adjusted OR 1.08, 95% CI 1.01-1.16, P=0.01), pneumothorax (adjusted OR 0.07, 95% CI 0.01-0.38, P=0.002), neutrophil count (adjusted OR 1.27, 95% CI 1.05-1.53, P=0.01) at 14 days, and hemoglobin level (adjusted OR 0.94, 95% CI 0.91-0.98; P=0.002) at 14 days after admission. The risk factor associated with death in the CPD-PJP group was neutrophil count (adjusted OR 1.19, 95% CI 0.99-1.43; P=0.05) at 14 days after admission. Conclusion: The risk factors for death were different between patients with PJP with and without chronic pulmonary disease. Early identification of these factors in patients with PJP and other underlying diseases may improve prognosis.

A new particle filter algorithm filtering motion artifact noise for clean electrocardiogram signals in wearable health monitoring system.

With the evolution of wearable systems, more and more people tend to wear wearable devices for health monitoring during sports. However, a large amount of motion artifact noise is introduced at this time, which is difficult to filter out due to its stochasticity. The amplitude and characteristics of motion artifact noise vary with changes in motion intensity. In order to filter out the motion artifact noise, the paperproposes a new particle algorithm, which can detect the intensity of the motion artifact for adaptive filtering, especiallysuitable for wearable health monitoring systems. In this algorithm, variational mode decomposition was first introduced to analyze the noisy electrocardiogram (ECG) signal in order to find the clean components. Then, the Laguerre estimation technique was applied to obtain an accurate ECG polar model. Taking this model as the state equation, a particle filter algorithm was defined to filter out the motion artifact noise. In the particle filter algorithm, we defined a parameter γ whose values were obtained from the six-axis data of motion sensor MPU6050 in our wearable device. This parameter γ could reflect the current noise levels and adaptively update the particle weights. Finally, some exercise experiments proved that the parameter γ could map the motion artifacts in real time and also demonstrated the superiority of the algorithm in terms of signal-to-noise ratio improvement and error reduction compared to other algorithms. The new particle filter algorithm proposed in this paper combines the six-axis data (three-axis accelerometer and three-axis gyroscope) with the ECG signal to effectively eliminate a large amount of motion artifact noise, thus solving the problem of excess noise from wearable devices when people are exercising, allowing them to accurately obtain real-time ECG health information.

Nomograms for Death from Pneumocystis jirovecii Pneumonia in HIV-Uninfected and HIV-Infected Patients.

Purpose: Pneumocystis jirovecii pneumonia (PCP) is a major cause of death in immunocompromised patients. Many risk factors for poor prognosis have been reported, but few studies have created predictive models with these variables to calculate the death rate accurately. This study created nomogram models for the precise prediction of mortality risk in human immunodeficiency virus (HIV) uninfected and HIV-infected patients with PCP. Patients and Methods: A retrospective study was performed over a 10-year period to evaluate the clinical characteristics and outcomes of PCP in HIV-uninfected and HIV-infected adults treated in Beijing, China from 2010 to 2019. Univariate and multivariate logistic regression analyses were used to identify mortality risk factors to create the nomograms. Nomogram models were evaluated by using a bootstrapped concordance index, calibration plots and receiver operating characteristic (ROC) curves. Results: A total of 167 HIV-uninfected and 193 HIV-infected PCP patients were included in the study. Pneumothorax, duration of fever after admission, CD4+ T cells ≤100/µL and trimethoprim-sulfamethoxazole (TMP-SMX) combined with caspofungin (CAS) treatment were independent risk factors for death in HIV-uninfected PCP patients. We derived a well calibrated nomogram for mortality by using these variables. The area under the curve was 0.865 (95% confidence interval 0.799-0.931). Independent risk factors for death in HIV-infected PCP patients were pneumothorax, platelet (PLT) ≤80×109/L, haemoglobin (HGB) ≤90 g/L, albumin (ALB), cytomegalovirus (CMV) coinfection and TMP-SMX combined with CAS treatment. The nomogram showed good discrimination, with a C-index of 0.904 and excellent calibration. Conclusion: The nomograms which were derived may be useful tools for the precise prediction of mortality in HIV-uninfected and HIV-infected patients, but require validation in clinical practice.