Orthopedic Center of Chinese PLA, Urumqi General Hospital of Lanzhou Military Region,

Sphingosine-1-phosphate is a possible fibrogenic factor in glutea

High-Sensitivity C-Reactive Protein: An Independent Risk Factor for Left Ventricular Hypertrophy in Patients with Lupus Nephritis

Objective. To determine the prevalence of left ventricular hypertrophy (LVH) and its associated risk factors in lupus nephritis (LN) patients. Methods. 287 LN patients (age: 38.54 ± 13.31, 262 female) were recruited. Echocardiography and serum high-sensitivity C-reactive protein (hs-CRP) were measured. Their relationship was evaluated by univariate correlation analysis and multivariate regression analysis. Results. The prevalence of LVH in this cohort was 21.25% (n = 61). Serum hs-CRP level was significantly elevated in patients with LVH compared to those without (8.03 (3.22–30.95) versus 3.93 (1.48–9.48) mg/L, P < .01), and correlated with left ventricular mass index (LVMI) (r = 0.314, P = .001). Multivariate regression analysis further confirmed that hs-CRP was an independent risk factor (β = 0.338, P = .002) for LVH in patients with LN. Conclusions. Our findings demonstrated that serum hs-CRP level is independently correlated with LVMI and suggested that measurement of hs-CRP may provide important clinical information to investigate LVH in LN patients

Serum IL-18 Is Closely Associated with Renal Tubulointerstitial Injury and Predicts Renal Prognosis in IgA Nephropathy

Background. IgA nephropathy (IgAN) was thought to be benign but recently found it slowly progresses and leads to ESRD eventually. The aim of this research is to investigate the value of serum IL-18 level, a sensitive biomarker for proximal tubule injury, for assessing the histopathological severity and disease progression in IgAN. Methods. Serum IL-18 levels in 76 IgAN patients and 36 healthy blood donors were measured by ELISA. We evaluated percentage of global and segmental sclerosis (GSS) and extent of tubulointerstitial damage (TID). The correlations between serum IL-18 levels with clinical, histopathological features and renal prognosis were evaluated. Results. The patients were 38.85 ± 10.95 years old, presented with 2.61 (1.43∼4.08) g/day proteinuria. Serum IL-18 levels were significantly elevated in IgAN patients. Baseline serum IL-18 levels were significantly correlated with urinary protein excretion (r = 0.494, P = 0.002), Scr (r = 0.61, P < 0.001), and eGFR (r = −0.598, P < 0.001). TID scores showed a borderline significance with serum IL-18 levels (r = 0.355, P = 0.05). During follow-up, 26 patients (34.21%) had a declined renal function. Kaplan-Meier analysis found those patients with elevated IL-18 had a significant poor renal outcome (P = 0.03), and Cox analysis further confirmed that serum IL-18 levels were an independent predictor of renal prognosis (β = 1.98, P = 0.003)

The Altered Reconfiguration Pattern of Brain Modular Architecture Regulates Cognitive Function in Cerebral Small Vessel Disease

Background: Cerebral small vessel disease (SVD) is a common cause of cognitive dysfunction. However, little is known whether the altered reconfiguration pattern of brain modular architecture regulates cognitive dysfunction in SVD.Methods: We recruited 25 cases of SVD without cognitive impairment (SVD-NCI) and 24 cases of SVD with mild cognitive impairment (SVD-MCI). According to the Framingham Stroke Risk Profile, healthy controls (HC) were divided into 17 subjects (HC-low risk) and 19 subjects (HC-high risk). All individuals underwent resting-state functional magnetic resonance imaging and cognitive assessments. Graph-theoretical analysis was used to explore alterations in the modular organization of functional brain networks. Multiple regression and mediation analyses were performed to investigate the relationship between MRI markers, network metrics and cognitive performance.Results: We identified four modules corresponding to the default mode network (DMN), executive control network (ECN), sensorimotor network and visual network. With increasing vascular risk factors, the inter- and intranetwork compensation of the ECN and a relatively reserved DMN itself were observed in individuals at high risk for SVD. With declining cognitive ability, SVD-MCI showed a disrupted ECN intranetwork and increased DMN connection. Furthermore, the intermodule connectivity of the right inferior frontal gyrus of the ECN mediated the relationship between periventricular white matter hyperintensities and visuospatial processing in SVD-MCI.Conclusions: The reconfiguration pattern of the modular architecture within/between the DMN and ECN advances our understanding of the neural underpinning in response to vascular risk and SVD burden. These observations may provide novel insight into the underlying neural mechanism of SVD-related cognitive impairment and may serve as a potential non-invasive biomarker to predict and monitor disease progression

Identification of PDCD1 as a potential biomarker in acute rejection after kidney transplantation via comprehensive bioinformatic analysis

BackgroundAcute rejection is a determinant of prognosis following kidney transplantation. It is essential to search for novel noninvasive biomarkers for early diagnosis and prompt treatment.MethodsGene microarray data was downloaded from the Gene Expression Omnibus (GEO) expression profile database and the intersected differentially expressed genes (DEGs) was calculated. We conducted the DEGs with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Distribution of immune cell infiltration was calculated by CIBERSORT. A hub gene marker was identified by intersecting the rejection-related genes from WGCNA and a selected KEGG pathway—T cell receptor signaling pathway (hsa04660), and building a protein-protein interaction network using the STRING database and Cytoscape software. We performed flow-cytometry analysis to validate the hub gene.ResultsA total of 1450 integrated DEGs were obtained from five datasets (GSE1563, GSE174020, GSE98320, GSE36059, GSE25902). The GO, KEGG and immune infiltration analysis results showed that AR was mainly associated with T cell activation and various T-cell related pathways. Other immune cells, such as B cells, Macrophage and Dendritic cells were also associated with the progress. After utilizing the WGCNA and PPI network, PDCD1 was identified as the hub gene. The flow-cytometry analysis demonstrated that both in CD4+ and CD8+ T cells, PD1+CD57-, an exhausted T cell phenotype, were downregulated in the acute rejection whole blood samples.ConclusionsOur study illustrated that PDCD1 may be a candidate diagnostic biomarker for acute kidney transplant rejection via integrative bioinformatic analysis

Aggregation-induced emission (AIE) dye loaded polymer nanoparticles for gene silencing in pancreatic cancer and their in vitro and in vivo biocompatibility evaluation

We have developed aggregation-induced emission (AIE) dye loaded polymer nanoparticles with deep-red emission for siRNA delivery to pancreatic cancer cells. Two US Food and Drug Administration (FDA) approved surfactant polymers, Pluronics F127 and PEGylated phospholipid, were used to prepare the dye-loaded nanoparticle formulations and they can be used as nanovectors for gene silencing of mutant K-ras in pancreatic cancer cells. The successful transfection of siRNA by the developed nanovectors was confirmed by the fluorescent imaging and quantified through flow cytometry. Quantitative real time polymerase chain reaction (PCR) indicates that the expression of the mutant K-ras oncogene from the MiaPaCa-2 pancreatic cancer cells has been successfully suppressed. More importantly, our in vivo toxicity study has revealed that both the nanoparticle formulations are highly biocompatible in BALC/c mice. Overall, our results suggest that the AIE dye-loaded polymer nanoparticle formulations developed here are suitable for gene delivery and have high potential applications in translational medicine research

The chemical profiling of Salvia plebeia during different growth periods and the biosynthesis of its main flavonoids ingredients

Salvia plebeia (Lamiaceae) is a valuable medicinal plant widely distributed across Asia and Oceania. However, the composition and accumulation patterns of its active ingredients in different organs during the growth and their biosynthetic mechanism remain unknown. Therefore, we conducted metabolite profiling, transcriptomic analysis, and biological functional verification to explore the distribution, accumulation, and biosynthesis mechanisms of flavonoids in S. plebeia. We identified 70 metabolites including 46 flavonoids, 16 phenolic acids, seven terpenoids, and one organic acid, of which 21 were previously unreported in S. plebeia. Combining metabolomic-transcriptomic analysis and biological functional verification, we identified the key genes involved in biosynthesis of its main active ingredients, hispidulin and homoplantaginin, including SpPAL, SpC4H, Sp4CL2, Sp4CL5, SpCHS1, SpCHI, SpFNS, SpF6H1, SpF6OMT1, SpF6OMT2, SpUGT1, SpUGT2, and SpUGT3. Using the identified genes, we reconstructed the hispidulin and homoplantaginin biosynthesis pathways in Escherichia coli, and obtained a yield of 5.33 and 3.86 mg/L for hispidulin and homoplantaginin, respectively. Our findings provide valuable insights into the changes in chemical components in different organs of S. plebeia during different growth and harvest stages and establishes a foundation for identifying and synthesizing its active components

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Nonlinear Dynamic Characteristic Analysis Method Based on Load Angle of Two-Stage Magnetic Gearbox for Wind Turbine

The magnetic gearbox for wind turbine has the potential virtue of less maintenance, improved reliability, and overload protection. Dynamic performance analysis plays a key role in its optimal design and ensuring its stable operation. But so far, there are few unified and effective methods for dynamic performance analysis of magnetic gearbox especially for multistage magnetic gearbox. Thus, a nonlinear dynamic analysis method based on load angle is proposed for two-stage magnetic gearbox in this paper. First, the nonlinear dynamic model of two-stage magnetic gearbox is established based on load angle. Second, the analytical expressions of load angle and magnetic torque of magnetic gearbox facing instantaneous shock are obtained by Taylor expansion based on load angle. Third, the dynamic performance of magnetic gearbox under different operating conditions is analyzed. Finally, the simulation results are discussed, and the results show that the accuracy of the proposed analytical method is comparable to that of Runge-Kutta method, which verifies the effectiveness of the proposed method and facilitates its application to the fast dynamic evaluation and optimal design of multistage magnetic gearbox