Pentacarbonyl Derivatives of Polydentate Phosphines

Four phosphines (Ph2P)2C=CHPPh2, (p-tol)2PCH2P(p-tol)2, (o-tol)2PCH2P(o-tol)2, Ph2PCH2P(p-tol)2 and their pentacarbonyltungsten complexes have been prepared and studied as part of a continuous investigation of polydentate phosphines that are coordinated as monodentate ligands. The ligand, (Ph2P)2C=CHPPh2, was prepared by base-catalyzed addition of Ph2PH to Ph2PC=CPPh2. Reaction of this ligand with (OC)5WNH2Ph led to formation of a monodentate complex in which the diphenylphosphino group attached to CH=C is coordinated to tungsten, (OC)5W[η1-PPh2CH=C(PPh2)2]. Similar reactions led to the formation of (OC)5W[η1-P(p-tol)2CH2P(p-tol)2] and (OC)5W[η1-P(o-tol)2CH2P(o-tol)2]. The linkage isomers, (OC)5W[η1-PPh2CH2P(p-tol)2] (A) and (OC)5W[η1-P(p-tol)2CH2PPPh2] (B) were also studied and their rates of isomerization in chloroform were followed with 31P{1H} NMR spectroscopy. Rate constants for the conversion of A to B and B to A are (1.4 ± 0.6) x 10-6 s-1 and (6.9 ± 0.3) x 10-7 s-1 at 55°C, respectively. The equilibrium constant, B/A, is 2.00

Association of Circulating MtDNA With CVD in Hemodialysis Patients and In Vitro Effect of Exogenous MtDNA on Cardiac Microvascular Inflammation

BACKGROUND: Chronic kidney disease (CKD) patients sustain a fairly high prevalence of cardiovascular disease (CVD). Microvascular inflammation is an early manifestation of CVD, and the released mitochondrial DNA (MtDNA) has been proposed to be a crucial integrator of inflammatory signals. Herein, the aim of this study was to determine the relationship between CVD, microvessel, and circulating MtDNA in the settings of uremia. METHODS: Forty-two maintenance hemodialysis (MHD) patients and 36 health controls were enrolled in this study. Plasma cell-free MtDNA was detected by TaqMan-based qPCR assay. CVD risk markers including high-sensitive C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), fibrinogen, and erythrocyte sedimentation rate (ESR) were measured by standard assays. Ten-year CVD risk was calculated from the Framingham risk score (FRS) model. In vitro study, human cardiac microvascular endothelial cells (HCMECs) were incubated with normal or uremic serum, with or without exogenous MtDNA. Intracellular toll-like receptor 9 (TLR9), adhesion molecule 1 (ICAM-1), MCP-1 and tumor necrosis factor-α (TNF-α) and cytosolic MtDNA were detected by qPCR. RESULTS: Plasma MtDNA in MHD patients was significantly higher than healthy controls (4.74 vs. 2.41 × 10 CONCLUSIONS: Overall, the present study suggests that MtDNA released into the circulation under the uremic toxin environment may adversely affect the cardiovascular system by exacerbating microvascular inflammation, and that reducing circulating MtDNA might be a future therapeutic strategy for the prevention of MHD-related CVD

SynthTab: Leveraging Synthesized Data for Guitar Tablature Transcription

Guitar tablature is a form of music notation widely used among guitarists. It captures not only the musical content of a piece, but also its implementation and ornamentation on the instrument. Guitar Tablature Transcription (GTT) is an important task with broad applications in music education and entertainment. Existing datasets are limited in size and scope, causing state-of-the-art GTT models trained on such datasets to suffer from overfitting and to fail in generalization across datasets. To address this issue, we developed a methodology for synthesizing SynthTab, a large-scale guitar tablature transcription dataset using multiple commercial acoustic and electric guitar plugins. This dataset is built on tablatures from DadaGP, which offers a vast collection and the degree of specificity we wish to transcribe. The proposed synthesis pipeline produces audio which faithfully adheres to the original fingerings, styles, and techniques specified in the tablature with diverse timbre. Experiments show that pre-training state-of-the-art GTT model on SynthTab improves transcription accuracy in same-dataset tests. More importantly, it significantly mitigates overfitting problems of GTT models in cross-dataset evaluation.Comment: Submitted to ICASSP202

Construction of index system for external risk factors of disease on large-scale farm based on the analytic hierarchy process

AbstractAnimal health risk analysis technology on large-scale farm is becoming more important, but the assessment of relevant external risk factors of disease spreading into pig farm is an complex multi-dimensional process. The analytic hierarchy process (AHP) has been accepted as a robust and flexible multi-criteria decision-making tool for dealing with complex decision problems. On this study, The index system of external risk factors on large-scale farm is built based on AHP. The result shows that farm management practices, Biosecurity and site are major risk factors and reveals AHP can be used in animal risk analysis for disease control and prevention

A role of STAT3 in Rho GTPase-regulated cell migration and proliferation.

Rho family GTPases and STAT3 act as mediators of cytokine and growth factor signaling in a variety of cellular functions involved in inflammation, tumorigenesis, and development. In the course of searching for their functional connections, we found by using STAT3 knock-out mouse embryonic fibroblasts that RhoA, Rac1, and Cdc42 could cause nonspecific activation of STAT3 promoter-driven luciferase reporter in the absence of STAT3, raising concerns to a body of literature where STAT3 was associated with Rho GTPases based on the reporter system. We also found that although active RhoA, Rac1, and Cdc42 could all mediate Ser-727 and Tyr-705 phosphorylation and nuclear translocation of STAT3, the Rho GTPases were able to induce STAT3 activation independently of the interleukin-6 autocrine pathway, and active RhoA, Rac1, or Cdc42 could not form a stable complex with STAT3 as previously suggested, indicating an unappreciated mechanism of STAT3 activation by the Rho GTPases. The RhoA-induced STAT3 activation partly depended on Rho-associated kinase (ROK) and involved multiple effector signals as revealed by the examination of effector domain mutants of RhoA. Genetic deletion of STAT3 led to a loss of response to RhoA in myosin light chain phosphorylation and actin stress fiber induction but sensitized the cells to RhoA or ROK-stimulated cell migration. STAT3 was required for the RhoA-induced NF-kappaB and cyclin D1 transcription and was involved in NF-kappaB nuclear translocation. Furthermore, loss of STAT3 expression inhibited RhoA-promoted cell proliferation and blocked RhoA or ROK induced anchorage-independent growth. These phenotypic changes in STAT3-/- cells could be rescued by reconstituting STAT3 gene. Our studies carried out in STAT3 null cells demonstrate unambiguously that STAT3 represents an essential effector pathway of Rho GTPases in regulating multiple cellular functions including actin cytoskeleton reorganization, cell migration, gene activation, and proliferation

Alzheimer’s disease biomarkers in patients with obstructive sleep apnea hypopnea syndrome and effects of surgery: A prospective cohort study

BackgroundObstructive sleep apnea hypopnea syndrome (OSAHS) may cause Alzheimer’s disease (AD), t-tau, p-tau, Aβ42, and Aβ40 are important elements in the process of AD, and changes in the levels of these biomarkers may affect the cognitive functioning of patients. Our objective was to investigate whether uvulopalatopharyngoplasty could reduce the plasma levels of AD biomarkers in OSAHS patients and the potential correlations of AD biomarkers with cognitive impairment and sleepiness, and explore the independent influencing factors of cognitive function.MethodsAlzheimer’s disease biomarkers were measured in the plasma of 35 patients with severe OSAHS requiring surgical treatment and 16 healthy controls without OSAHS. The cognitive function and sleepiness of OSAHS patients was also evaluated. The case group was given uvulopalatopharyngoplasty and followed at the postoperative sixth month, the follow-up cases were 27, and plasma AD biomarker levels, cognitive function, and sleepiness were re-evaluated. The preoperative and postoperative AD biomarker levels OSAHS patients were compared with each other and those of the control group. Linear stepwise regression and lasso regression were used to explore the relationships of AD biomarkers with cognitive impairment and sleepiness.ResultsSignificantly higher Aβ40, t-tau, p-tau in plasma were observed preoperatively in OSAHS patients comparing to controls (29.24 ± 32.52 vs. 13.18 ± 10.78, p = 0.049; 11.88 ± 7.05 vs. 7.64 ± 4.17, p = 0.037; 26.31 ± 14.41 vs. 17.34 ± 9.12, p = 0.027). The sixth month of postoperation, the plasma AD biomarkers (Aβ42, Aβ40, t-tau, p-tau) in plasma levels decreased significantly (0.23 ± 0.17 vs. 0.20 ± 0.16, p = 0.0001; 29.24 ± 32.52 vs. 23.52 ± 24.46, p = 0.0046; 11.88 ± 7.05 vs. 8.88 ± 6.21, p = 0.0001;26.31 ± 14.41 vs. 20.43 ± 10.50, p = 0.0001). A comparison of MMSE and ESS scores from before to after surgery revealed obvious differences (27.14 ± 1.65 vs. 29.07 ± 1.78, p = 0.0001; 11.91 ± 4.84 vs. 5.89 ± 2.83, p = 0.0001). Changes in cognitive function and sleepiness scores from before to after uvulopalatopharyngoplasty were significantly correlated with AD biomarkers. Body mass index and t-tau were potential influencing factors cognitive function.ConclusionObstructive sleep apnea hypopnea syndrome can increase plasma AD biomarkers levels. Uvulopalatopharyngoplasty can improve patients’ cognition and sleepiness, and the mechanism may be related to changes in plasma AD biomarkers. Higher AHI and higher t-tau level were identified as independent risk factors for cognitive decline

Resistance-gene-directed discovery of a natural-product herbicide with a new mode of action.

Bioactive natural products have evolved to inhibit specific cellular targets and have served as lead molecules for health and agricultural applications for the past century1-3. The post-genomics era has brought a renaissance in the discovery of natural products using synthetic-biology tools4-6. However, compared to traditional bioactivity-guided approaches, genome mining of natural products with specific and potent biological activities remains challenging4. Here we present the discovery and validation of a potent herbicide that targets a critical metabolic enzyme that is required for plant survival. Our approach is based on the co-clustering of a self-resistance gene in the natural-product biosynthesis gene cluster7-9, which provides insight into the potential biological activity of the encoded compound. We targeted dihydroxy-acid dehydratase in the branched-chain amino acid biosynthetic pathway in plants; the last step in this pathway is often targeted for herbicide development10. We show that the fungal sesquiterpenoid aspterric acid, which was discovered using the method described above, is a sub-micromolar inhibitor of dihydroxy-acid dehydratase that is effective as a herbicide in spray applications. The self-resistance gene astD was validated to be insensitive to aspterric acid and was deployed as a transgene in the establishment of plants that are resistant to aspterric acid. This herbicide-resistance gene combination complements the urgent ongoing efforts to overcome weed resistance11. Our discovery demonstrates the potential of using a resistance-gene-directed approach in the discovery of bioactive natural products

Crystal structure of 3-methyl-2-oxo-2H-chromen-7-yl propionate, C13H12O4

Abstract C13H12O4, triclinic, P1̄ (no. 2), a = 6.141(5) Å, b = 8.108(6) Å, c = 12.234(9) Å, α = 79.257(12)°, β = 76.820(12)°, γ = 74.687(11)°, V = 566.8(7) Å3, Z = 2, R gt(F) = 0.0515, wR ref(F 2) = 0.1575, T = 296(2) K