Jackknife approach to the estimation of mutual information.

Quantifying the dependence between two random variables is a fundamental issue in data analysis, and thus many measures have been proposed. Recent studies have focused on the renowned mutual information (MI) [Reshef DN, et al. (2011) Science 334:1518-1524]. However, "Unfortunately, reliably estimating mutual information from finite continuous data remains a significant and unresolved problem" [Kinney JB, Atwal GS (2014) Proc Natl Acad Sci USA 111:3354-3359]. In this paper, we examine the kernel estimation of MI and show that the bandwidths involved should be equalized. We consider a jackknife version of the kernel estimate with equalized bandwidth and allow the bandwidth to vary over an interval. We estimate the MI by the largest value among these kernel estimates and establish the associated theoretical underpinnings.

Microecological treatment of hyperuricemia using Lactobacillus from pickles.

BACKGROUND: Hyperuricemia is one of the important risk factors for gout, arteriosclerosis, cardiovascular and cerebrovascular disease. Lactobacillus has attracted much attention due to its role in the regulation of intestinal function and tumor resistance, but its ability to reduce uric acid is unclear. Pickles are a traditional fermented food rich in lactic acid bacteria (LAB). RESULTS: LAB strains were isolated from 18 pickles and their tolerance to acid bile salts, trypsin, pepsin were evaluated after screening by nucleoside degradation. 16S rDNA sequence analysis was used to identify LAB strains. Furthermore, we established rat model of hyperuricemia and demonstrated that Lactobacillus could alleviate hyperuricemia and reduce kidney injury. CONCLUSION: This study suggests that microecological treatment with Lactobacillus represents a feasible option for patients with chronic hyperuricemia.

Comparative Cytotoxicity induced by Zinc Oxide Nanoparticles in Human Prostate Cells.

Despite increasing biomedical applications of zinc oxide nanoparticles (ZnO NPs), there is a lack of information concerning the biological effects of ZnO NPs on human cells. The purpose of this study was to assess the comparative cytotoxicity in human prostate cells (PC-3 and RWPE-1) exposure to 20-nm ZnO NPs. Exposure to concentrations from 0 to 50 µg/mL of ZnO NPs reduced cell viability of PC-3 cells in a dose- and time-dependent manner; whereas it did not affect RWPE-1 cells. A dose-dependent increase in LDH leakage and intracellular reactive oxygen species was observed in PC-3 cells but not in RWPE-1 cells exposure to ZnO NPs at concentrations of 8 ˜ 50 µg/mL for 24 h (P < 0.05). That the percentage of apoptotic cells increased significantly was observed in PC-3 cells induced by ZnO NPs at 10 µg/mL exposure for 8 h. Our results showed that ZnO NPs induced in vitro preferential cytotoxicity in the human prostate cancer cells. We indicated that the different cytotoxicity of ZnO NPs is likely due to the different cell-nanoparticle interaction and response behavior rather than to hydrodynamic sizes of particles. It is suggested that ZnO NPs are expected to find a very promising targeting therapeutic application for human prostate cancer.

Parallel path detection for fraudulent accounts in banks based on graph analysis.

This article presents a novel parallel path detection algorithm for identifying suspicious fraudulent accounts in large-scale banking transaction graphs. The proposed algorithm is based on a three-step approach that involves constructing a directed graph, shrinking strongly connected components, and using a parallel depth-first search algorithm to mark potentially fraudulent accounts. The algorithm is designed to fully exploit CPU resources and handle large-scale graphs with exponential growth. The performance of the algorithm is evaluated on various datasets and compared with serial time baselines. The results demonstrate that our approach achieves high performance and scalability on multi-core processors, making it a promising solution for detecting suspicious accounts and preventing money laundering schemes in the banking industry. Overall, our work contributes to the ongoing efforts to combat financial fraud and promote financial stability in the banking sector.

Association of Office and Ambulatory Blood Pressure with Left Ventricular Structure and Function in Hypertensive Patients.

Objective: The current study was to evaluate the association of office blood pressure (OBP) and 24h ambulatory blood pressure (ABP) with left ventricular (LV) structure and function in hypertensive patients. Whether the association was modified by sex was also evaluated. Methods: A total of 694 hypertensive patients without cardiovascular disease were retrospectively included from the inpatient clinic. Regression analysis was performed to evaluate the association of OBP and 24h ABP parameters with LV mass index (LVMi), e' velocity and left ventricular hypertrophy (LVH) with adjustment for covariates including age, obesity, diabetes mellitus, obstructive sleep apnea, estimated glomerular filtration rate and antihypertensive drugs. Results: There was no difference in OBP by sex. Compared to women, men had a higher 24h (132.6 ± 11.3 vs 129.3 ± 10.0 mm Hg), daytime (136.6 ± 12.9 vs 132.8 ± 9.5 mm Hg) and nighttime (130.3 ± 9.2 vs 125.1 ± 6.6 mm Hg) SBP. The proportion of patients with non-dipping pattern and reverse dipper pattern was also higher in men. In the overall participants, 24h, daytime and nighttime SBP, non-dipping and reverse dipper pattern were associated with LVMi, e' velocity and LVH, which were not observed in OBP. The magnitude of the association between 24h, daytime and nighttime SBP, non-dipping and reverse dipper pattern with LVMi, e' velocity and LVH was stronger in men than in women (P-value for interaction <0.05). Conclusion: Twenty-four-hour ABP appears to be better than OBP in association with LV structural and functional alterations, and this association was modified by sex.

The position of entry point in total knee arthroplasty is associate with femoral bowing both in coronal and sagittal planes.

Objective: To investigate the femoral entry point of the intramedullary (IM) guiding rod applied to total knee arthroplasty (TKA) in Chinese subjects and the relationship with femoral bowing in the coronal and sagittal planes through three-dimensional (3D) validation methods. Methods: Computed tomography (CT) images of 80 femurs in Chinese subjects were imported into Mimics 19.0 to construct 3D models. All operations were conducted by Rhinoceros software 5.0. The position of the IM rod entry point was assessed by calculating the distance between the entry point and the apex of the intercondylar notch (AIN) in the coronal and sagittal planes. The coronal femoral bowing angle (cFBA) and sagittal femoral bowing angle (sFBA) were also measured. Results: The average optimal entry point was 0.17 mm medial and 12.37 mm anterior to the AIN in males, while it was 0.02 mm lateral and 16.13 mm anterior to the AIN in females. There was a significant difference between males and females in the sagittal plane (t = -6.570, p = 0.000). The mean cFBA was 1.68 ± 2.29°, and the mean sFBA was 12.66 ± 1.98°. The sFBA was strongly correlated with the anterior distance of the proper entry point, and the cFBA was moderately correlated with the lateral distance of the proper entry point. Conclusions: There was a strong correlation between the position of the entry point and the femoral bowing angle in both the coronal and sagittal planes. Thus, to achieve better alignment, the position of the entry point should be measured individually based on femoral bowing.

A New Reference Axis for Tibial Component Rotation in Total Knee Arthroplasty: A Three-dimensional Computed Tomography Analysis.

The purpose of this study was to introduce a new reference axis for tibial rotation in total knee arthroplasty (TKA) and verify its reliability. A consecutive series of 80 knees that underwent TKA from 2018 to 2020 as well as 80 healthy knees were analyzed using a three-dimensional tibial model. A coordinate system was established based on the standard TKA tibial cut. The line connecting the lateral-tibial eminence and the medial 1/3rd of the tibial tubercle or the medial border of the tibial tubercle was identified as the lateral eminence line (LE line) and the medial lateral eminence line (MLE line), respectively. To evaluate the reliability of the new reference axis, Akagi's line, the medial third of the tibial tubercle (1/3 line) was compared with the LE and MLE lines by measuring the angle between the lines and the Z-axis. In the coronal view, the intersection angle (TPA), which is composed of the line connecting the center of the medial and lateral tibial plateau with the Z-axis, was measured. The mean angle between Akagi's line and the Z-axis in the healthy group and the osteoarthritis (OA) group was 87.57 ± 3.48° and 87.61 ± 3.47°, respectively. The mean angle between the LE line and Z-axis in the healthy and OA groups was 87.15 ± 4.13° and 86.78 ± 3.95°, respectively. A weak correlation was found between the TPA and Akagi's line and the 1/3 line. A moderate correlation was observed between the TPA and LE lines. There were no significant differences between the healthy and OA groups (P > 0.05) in any of the four reference axes. The LE line showed excellent intra- and inter-observer reliability and reproducibility. The novel and easily drawn LE line is a preferable option for tibial component rotational alignment in TKA.

The Presence of Cartilage Affects Femoral Rotational Alignment in Total Knee Arthroplasty.

OBJECTIVE: To assess the difference between the posterior condylar angle (PCA) and the mechanical lateral distal femoral angle (mLDFA) in the osseous and cartilaginous contours in a non-arthritic Chinese population. METHODS: Computed tomography (CT) and magnetic resonance imaging (MRI) were obtained from 83 patients with knee injuries before arthroscopy, and femur and distal femoral cartilage three-dimensional (3D) models were constructed. The 3D cartilage model was arranged to share physical space with the 3D femoral model, and then PCA and mLDFA were measured on the osseous and cartilaginous contours, respectively. The differences between the measurements with and without cartilage were evaluated. RESULTS: The average PCA with cartilage was 2.88 ± 1.35° and without was 2.73 ± 1.34°. The difference was significant in all patients and females but not in males. The average mLDFA with cartilage was 84.73 ± 2.15° and without cartilage was 84.83 ± 2.26°, but the difference was statistically insignificant in all groups. CONCLUSION: PCA on the osseous and cartilaginous contours significantly differed with and without cartilage in the female group, suggesting that cartilage thickness should be considered during preoperative femoral rotational resection planning.

Developing a novel calcium magnesium silicate/graphene oxide incorporated silk fibroin porous scaffold with enhanced osteogenesis, angiogenesis and inhibited osteoclastogenesis.

Recently, biofunctional ions (Mg2+, Si4+, etc) and graphene derivatives are proved to be promising in stimulating bone formation. In this study, a novel inorganic/organic composite porous scaffold based on silk fibroin (SF), graphene oxide (GO), and calcium magnesium silicate (CMS) was developed for bone repair. The porous scaffolds obtained by lyophilization showed a little difference in pore structure while GO and CMS displayed a good interaction with SF matrix. The addition of CMS with good mineralization potential and sustainedly release ability of biofunctional ions (Ca2+, Mg2+and Si4+) increased the strength of SF scaffolds a little and facilitated the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) by upregulating bone formation-related genes (ALP, COL1, OC and Runx2). The further incorporation of GO in SF scaffolds enhanced the compressive strength and water retention, and also remarkably promoted the osteogenic differentiation of BMSCs. Besides, the angiogenesis of human umbilical vein endothelial cells was significantly promoted by CMS/GO/SF scaffold extract through the upregulation of angiogenesis genes (eNOs and bFGF). Moreover, the osteoclastic formation ability of RAW264.7 cells was suppressed by the released ions from CMS/GO/SF scaffold through the down-regulation of CAK, MMP9 and TRAP. The promoted osteogenesis, angiogenesis and inhibited osteoclastogenesis functions of CMS/GO/SF composite scaffold may enable it as a novel therapy for bone repair and regeneration.

Treatment with metformin prevents myocardial ischemia-reperfusion injury via STEAP4 signaling pathway.

OBJECTIVES: This study aims to investigate the underlying mechanism of metformin in reducing myocardial apoptosis and improving mitochondrial function in rats and H9c2 cells subjected with myocardial ischemia-reperfusion injury (I/R). METHOD: Following pretreatment with metformin, male Sprague-Dawley (SD) rats were used to establish an ischemia-reperfusion (I/R) model in vivo. Serum creatinine kinase-MB (CK-MB) and cardiac troponin T (cTnT) levels were examined by ELISA. Infarct size and apoptosis were measured by TTC staining and TUNEL assay. Pathological changes were evaluated by HE staining. H9c2 cells were used to establish a hypoxia-reoxygenation (H/R) model in vitro. Cell apoptosis and mitochondrial membrane potential (MMP) were examined by flow cytometry and Rhodamine 123. The expression levels of STEAP4, Bcl-2, Bax and GAPDH in both myocardial tissues and H9c2 cells were determined by western blotting. RESULTS: We found that metformin decreased infarct size, increased expression of STEAP4, mitigated myocardial apoptosis and increased mitochondrial membrane potential (MMP) when the models were subjected to H/R or I/R injuries. However, STEAP4 knockdown significantly abrogated the beneficial effect of metformin. CONCLUSIONS: We further demonstrated the protective effect of metformin on cardiomyocytes, which might be at least partly attributable to upregulation of STEAP4. Therefore, STEAP4 might be a new target to decrease apoptosis and rescue mitochondrial function in myocardial ischemia-reperfusion injury.

[In vitro biocompatibility of novel absorbable hydroxyapatite and AO artificial bone beta-tricalcium phosphate with rhesus bone marrow stromal cells].

OBJECTIVE: To study the in vitro biocompatibility of novel hydroxyapatite (HA) and AO artificial bone beta-tricalcium phosphate (beta-TCP) with rhesus bone marrow stromal cells (rBMSCs) . METHODS: The third passage of rBMSCs were cultured with HA and beta-TCP respectively, with the cells cultured without the materials as the control. The morphology and proliferation of cells were observed by inverted phase-contrast microscope and scanning electron microscope (SEM). MTT assay was used to semiquantitatively evaluate the cell proliferation. RESULTS: The rBMSC cocultured with HA exhibited good growth as observed under inverted phase-contrast microscope, without significant difference from the cells in the control group. Some small particles were seen pealing off from beta-TCP, and some of the cells died. Under SEM, rBMSCs showed good adhesion to HA with obvious proliferation, but the ratio of adhesive cells was not as high as that in beta-TCP group. MTT assay showed no significant difference in the cell number between HA and the control groups, but the cell number in beta-TCP group was notably less than that of control group. CONCLUSION: Novel HA has good biocompatibility with rBMSCs for bone tissue engineering, and AO artificial bone still needs improvement to serve as scaffold material for BMSCs.

Efficacy of prevascularization for segmental bone defect repair using ß-tricalcium phosphate scaffold in rhesus monkey.

Although small animal model (rabbit) showed successful bone defect repair using prevascularized tissue-engineered bone grafts (TEBG), large animal (rhesus monkey) studies are still needed to extrapolate the findings from animal data to humans. In current study, we investigated the efficacy of prevascularized TEBG for segmental bone defect repair in rhesus monkey. The segmental diaphyseal defects were created in both tibias. In group A, the defect was filled with prevascularized MSCs/scaffold prepared by inserting saphenous vascular bundle into the side groove and a fascia flap coverage; In group B, the defect was filled with MSCs/scaffold with a fascia flap coverage; In group C, the defect was filled with MSCs/scaffold; In group D, the defect was filled with only scaffold. The angiogenesis and new bone formation were compared among groups at 4, 8, and 12 weeks postoperatively. The results showed the prevascularized TEBG in group A could augment new bone formation and capillary vessel in-growth. It had significantly higher values of vascularization and radiographic grading score compared with other groups. In conclusion, the in vivo experiment data of prevascularized TEBG was further enriched from small to large animal model. It implies that prevascularized TEBG has great potentials in clinical applications.