Gujin Dan is a Chinese medicine formulation that stimulates cell proliferation and differentiation by controlling multiple genes involved in MC3T3-E1 cells

Background: With the development of Traditional Chinese medicine (TCM) in recent years, the use of TCM in the treatment of osteoporosis has received much attention and research. Gujin Dan (GJD) is one of the representative Chinese medicine formulations that work synergistically with 19 herbs and has been used for decades to treat cervical spondylosis, lumbar disc herniation, osteoarthritis and osteoporosis. However, the exact molecular mechanism by which GJD is used to strengthen bones in the treatment of osteoporosis remains largely unknown. / Methods: In this study, an aqueous extract of GJD was prepared and its components were identified by high-performance liquid chromatography (HPLC). The effect of GJD aqueous extract on MC3T3-E1 cells was determined by Cell Counting Kit-8 (CCK-8) assay, alkaline phosphatase (ALP), and alizarin red S staining (ARS), combined with RNA sequencing (RNA-seq) and qRT-PCR. / Results: Our study showed that GJD significantly promoted the proliferation of MC3T3-E1 cells, as well as the synthesis and mineralisation of the extracellular matrix. GJD significantly increased the expression levels of genes that promote cell proliferation such as Adamts1, Mcam, Cyr61, Fos, Cebpd, Fosl2, Sirt1, Nipbl, Sema3c and Kcnq1ot1, up-regulated genes that inhibit apoptosis such as Gadd45a, Birc3, up-regulated genes that inhibit osteoclastogenesis such as Bcl6, Nfkbiz, Clcf1, Bcl3, Lgals3, Wisp1, Dusp1 and Fblim1, up-regulated genes that promote MC3T3-E1 cell differentiation such as Junb, Egr1, Klf10, Atf6, Malat1, Btg2, Sertad4, Zfyve16, Tet2, Creb5, Snai2, Fam46a, Calcrl and Pdzrn3. In addition, GJD mildly upregulated the expression levels of gene markers such as Atf4, Fn1, Usp7, Sox4, Col16a1, Spp1, Bmp1, Runx2, Bglap, Col12a1, and Alpl in osteoblasts. / Conclusions: Our results show that GJD promotes the differentiation and proliferation of MC3T3-E1 cells, inhibits osteoclast formation, and prevents osteoblast apoptosis. The present study significantly improves the current understanding of the molecular effects of GJD on MC3T3-E1 cells. This study also provides a new strategy for the further use of Chinese medicinal preparations against bone metabolism-related diseases

Analisis Portofolio Optimal Dengan Single Index Model Untuk Meminimumkan Risiko Bagi Investor Di Bursa Efek Indonesia (Studi Pada Saham Indeks Kompas 100 Periode Februari 2010-juli 2014)

Investments can be made in the capital market, capital market instruments which are mostly attractive for investors is stock. Stock provides a return in the form of capital gains and dividends yield, not only noticing the return, investors need to pay attention to the investments risk. Unsystematis risk can be minimized by forming the optimal portfolio using one of the methods that is single index model. Study purpose is to knowing the stocks forming the optimal portfolio, the proportion of funds allocated to each stocks, the level of expectation return and risk.The method used in this research is descriptive research method with a quantitative approach. The samples used were 46 stocks in Kompas 100 Index, which meets the criteria for sampling. The results showed that 12 stocks of forming optimal portfolio, the stocks of which are UNVR, TRAM, MNCN, BHIT, JSMR, BMTR, GJTL, KLBF, AALI, CPIN, AKRA, and ASRI. Stock with highest proportion of funds is TRAM (23,52%), stock with lowest proportion of funds is AALI (0,62%). Portfolio which are formed will give return expectations by 3,05477% and carry the risk for about 0,1228%

Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome

INTRODUCTION Although much effort has been devoted to studying yeast in the past few decades, our understanding of this model organism is still limited. Rapidly developing DNA synthesis techniques have made a “build-to-understand” approach feasible to reengineer on the genome scale. Here, we report on the completion of a 770-kilobase synthetic yeast chromosome II (synII). SynII was characterized using extensive Trans-Omics tests. Despite considerable sequence alterations, synII is virtually indistinguishable from wild type. However, an up-regulation of translational machinery was observed and can be reversed by restoring the transfer RNA (tRNA) gene copy number. RATIONALE Following the “design-build-test-debug” working loop, synII was successfully designed and constructed in vivo. Extensive Trans-Omics tests were conducted, including phenomics, transcriptomics, proteomics, metabolomics, chromosome segregation, and replication analyses. By both complementation assays and SCRaMbLE (synthetic chromosome rearrangement and modification by loxP -mediated evolution), we targeted and debugged the origin of a growth defect at 37°C in glycerol medium. RESULTS To efficiently construct megabase-long chromosomes, we developed an I- Sce I–mediated strategy, which enables parallel integration of synthetic chromosome arms and reduced the overall integration time by 50% for synII. An I- Sce I site is introduced for generating a double-strand break to promote targeted homologous recombination during mitotic growth. Despite hundreds of modifications introduced, there are still regions sharing substantial sequence similarity that might lead to undesirable meiotic recombinations when intercrossing the two semisynthetic chromosome arm strains. Induction of the I- Sce I–mediated double-strand break is otherwise lethal and thus introduced a strong selective pressure for targeted homologous recombination. Since our strategy is designed to generate a markerless synII and leave the URA3 marker on the wild-type chromosome, we observed a tenfold increase in URA3 -deficient colonies upon I- Sce I induction, meaning that our strategy can greatly bias the crossover events toward the designated regions. By incorporating comprehensive phenotyping approaches at multiple levels, we demonstrated that synII was capable of powering the growth of yeast indistinguishably from wild-type cells (see the figure), showing highly consistent biological processes comparable to the native strain. Meanwhile, we also noticed modest but potentially significant up-regulation of the translational machinery. The main alteration underlying this change in expression is the deletion of 13 tRNA genes. A growth defect was observed in one very specific condition—high temperature (37°C) in medium with glycerol as a carbon source—where colony size was reduced significantly. We targeted and debugged this defect by two distinct approaches. The first approach involved phenotype screening of all intermediate strains followed by a complementation assay with wild-type sequences in the synthetic strain. By doing so, we identified a modification resulting from PCRTag recoding in TSC10 , which is involved in regulation of the yeast high-osmolarity glycerol (HOG) response pathway. After replacement with wild-type TSC10 , the defect was greatly mitigated. The other approach, debugging by SCRaMbLE, showed rearrangements in regions containing HOG regulation genes. Both approaches indicated that the defect is related to HOG response dysregulation. Thus, the phenotypic defect can be pinpointed and debugged through multiple alternative routes in the complex cellular interactome network. CONCLUSION We have demonstrated that synII segregates, replicates, and functions in a highly similar fashion compared with its wild-type counterpart. Furthermore, we believe that the iterative “design-build-test-debug” cycle methodology, established here, will facilitate progression of the Sc2.0 project in the face of the increasing synthetic genome complexity. SynII characterization. ( A ) Cell cycle comparison between synII and BY4741 revealed by the percentage of cells with separated CEN2-GFP dots, metaphase spindles, and anaphase spindles. ( B ) Replication profiling of synII (red) and BY4741 (black) expressed as relative copy number by deep sequencing. ( C ) RNA sequencing analysis revealed that the significant up-regulation of translational machinery in synII is induced by the deletion of tRNA genes in synII. </jats:sec

Energy storage properties of PVDF terpolymer/PMMA blends

Dielectrics can be used to store electric energy in capacitors and high-energy density of the materials is desirable to reduce the size or weight of capacitors. To improve the energy storage properties of poly(vinylidene fluoride–trifluoroethylene–chlorofluoroethylene) [P(VDF–TrFE–CFE)] terpolymer, P(VDF–TrFE–CFE)/poly(methyl methacrylate) (PMMA) blends were investigated in this study. By adding a small amount of PMMA into PVDF terpolymer (<5 wt%), the dielectric breakdown field of the blends can be improved as a result of the enhancement of elastic modulus of the blends. For the blends with <2.5 wt% PMMA, though their dielectric properties are reduced, under the same electric field, the energy density of the blends is almost the same as that of PVDF terpolymer. Consequently, the energy storage performance of the terpolymer can be improved by blending with a small amount of PMMA

Simple renal cyst as an independent risk factor for hypertension

Abstract A simple renal cyst (SRC) may increase the risk for hypertension. The authors examined the relationship between a SRC and hypertension in participants receiving physical examinations at Hebei Medical University. This study enrolled 66 883 participants who received physical examinations at our center from January 2012 to December 2017. Demographic data, medical history related to hypertension, hematological indexes, hypertension, and SRC subtype based on ultrasound examinations were examined. The relationship between SRC and hypertension was analyzed using univariate and multivariate logistic regression analysis in different models. Subgroup analysis and propensity score (PS) matching were also performed. Based on SRC subtype (unitary vs. multiple, small vs. large, unilateral vs. bilateral), a comprehensive scoring system was established to determine the effect of SRC load on hypertension. The results of univariate and multivariate analysis indicated that SRC was a risk factor for hypertension (P  .05). A SRC remained an independent risk factor for hypertension after PS matching (P < .01). Based on a scoring system that considered different SRC subtypes, the risk for hypertension increased with renal cyst load (P < .01). In conclusions, a SRC was an independent risk factor for hypertension, and there was a positive correlation between SRC load and hypertension. The risk of hypertension increased gradually with the size, number, and location of a SRC. Careful follow‐up or excision should be considered for patients with SRCs

Dynamic Plasma Lipidomic Analysis Revealed Cholesterol Ester and Amides Associated with Sepsis Development in Critically Ill Patients after Cardiovascular Surgery with Cardiopulmonary Bypass

Background: Sepsis in patients after cardiovascular surgery with cardiopulmonary bypass (CPB) has a high rate of mortality. We sought to determine whether changes in lipidomics can predict sepsis after cardiac surgery. Methods: We used high-performance liquid chromatography coupled to tandem mass spectrometry to explore global lipidome changes in samples from a prospective case-control cohort (30 sepsis vs. 30 nonsepsis) hospitalized with cardiovascular surgery. All patients were sampled before and within 48&ndash;72 h after surgery. A bioinformatic pipeline was applied to acquire reliable features and MS/MS-driven identifications. Furthermore, a multiple-step machine learning framework was performed for signature discovery and performance evaluation. Results: Compared with preoperative samples, 94 features were upregulated and 282 features were downregulated in the postoperative samples of the sepsis group, and 73 features were upregulated and 265 features were downregulated in the postoperative samples of the nonsepsis group. &ldquo;Autophagy&rdquo;, &ldquo;pathogenic Escherichia coli infection&rdquo; and &ldquo;glycosylphosphatidylinositol-anchor biosynthesis&rdquo; pathways were significantly enriched in the pathway enrichment analysis. A multistep machine learning framework further confirmed that two cholesterol esters, CE (18:0) and CE (16:0), were significantly decreased in the sepsis group (p &lt; 0.05). In addition, oleamide and stearamide were increased significantly in the postoperative sepsis group (p &lt; 0.001). Conclusions: This study revealed characteristic lipidomic changes in the plasma of septic patients before and after cardiac surgery with CPB. We discovered two cholesterol esters and two amides from peripheral blood that could be promising signatures for sepsis within a dynamic detection between the preoperative and postoperative groups

Continuous Positive Linear Association between the Monocyte to High-Density Lipoprotein Cholesterol Ratio and Hypertension: A Cross-Sectional Study

Background. Hypertension poses a major threat to human health, and inflammation is associated with hypertension. The monocyte to high-density lipoprotein cholesterol ratio (MHR) represents a new inflammatory indicator. However, the relationship between the MHR and hypertension remains unclear. The present study investigated the association of MHR with hypertension. Method. For this cross-sectional study, we continuously collected data from the Physical Examination Centre of the Second Hospital of Hebei Medical University (N = 6632). The data included patients’ demographic information and clinical information including blood pressure, blood biochemical measurements, and MHR. The relationship between the MHR and hypertension was examined using different methods in univariate and multivariate logistic analysis, smooth function analysis, the threshold saturation effect analysis and subgroup analysis. Results. The results showed that MHR was positively associated with hypertension without adjustment (odds ratio [OR] = 1.10, 95% confidence interval [CI]: 1.08–1.12, P<0.001). The positive association still existed in minimally and fully adjusted models (OR = 1.08, 95% CI: 1.06–1.10, P<0.001; OR = 1.07, 95% CI: 1.05–1.10, P<0.001). Smooth function analysis of a generalized additive model revealed a continuous positive linear association between the MHR and hypertension throughout all MHR data (OR = 1.07, 95% CI: 1.05–1.10, P<0.001). Subgroups analysis showed the homogeneity of the positive association among different subgroups. Conclusions. A continuous positive linear association was found between the MHR and hypertension in a health examination population