Bis(4-acetyl-3-methyl-1-phenyl-1H-pyrazol-5-olato-κ2 O,O′)bis­(N,N-dimethyl­formamide-κO)nickel(II)

The title complex, [Ni(C12H11N2O2)2(C3H7NO)2], lies on on an inversion center. The NiII ion is coordinated in a slightly distorted octa­hedral coordination enviroment by four O atoms from two bis-chelating 4-acety-3-methyl-1-phenyl-1H-pyrazol-5-olate ligands in the equatorial plane and two O atoms from two N,N-dimethyl­formamide ligands in the axial sites. In the crystal structure, weak inter­molecular π–π stacking inter­actions with centroid–centroid distances of 3.7467 (13) Å link mol­ecules into chains extending alongthe b axis

1,5-Dimethyl-4-(1-methyl-3-oxo-3-phenylprop-1-enyl­amino)-2-phenyl-1H-pyrazol-3(2H)-one

In the title compound, C21H21N3O2, an intra­molecular N—H⋯O inter­action generates an S(6) ring, which stablizes the enamine–keto tautomer. The S(6) ring makes dihedral angles of 33.07 (7), 56.50 (8) and 38.59 (8)°, respectively, with the benzoyl­acetone benzene ring and the anti­pyrine pyrazole and benzene rings

A proteomic view of Caenorhabditis elegans caused by short-term hypoxic stress

<p>Abstract</p> <p>Background</p> <p>The nematode <it>Caenorhabditis elegans </it>is both sensitive and tolerant to hypoxic stress, particularly when the evolutionarily conserved hypoxia response pathway HIF-1/EGL-9/VHL is involved. Hypoxia-induced changes in the expression of a number of genes have been analyzed using whole genome microarrays in <it>C. elegans</it>, but the changes at the protein level in response to hypoxic stress still remain unclear.</p> <p>Results</p> <p>Here, we utilized a quantitative proteomic approach to evaluate changes in the expression patterns of proteins during the early response to hypoxia in <it>C. elegans</it>. Two-dimensional difference gel electrophoresis (2D-DIGE) was used to compare the proteomic maps of wild type <it>C. elegans </it>strain N2 under a 4-h hypoxia treatment (0.2% oxygen) and under normoxia (control). A subsequent analysis by MALDI-TOF-TOF-MS revealed nineteen protein spots that were differentially expressed. Nine of the protein spots were significantly upregulated, and ten were downregulated upon hypoxic stress. Three of the upregulated proteins were involved in cytoskeletal function (LEV-11, MLC-1, ACT-4), while another three upregulated (ATP-2, ATP-5, VHA-8) were ATP synthases functionally related to energy metabolism. Four ribosomal proteins (RPL-7, RPL-8, RPL-21, RPS-8) were downregulated, indicating a decrease in the level of protein translation upon hypoxic stress. The overexpression of tropomyosin (LEV-11) was further validated by Western blot. In addition, the mutant strain of <it>lev-11(x12</it>) also showed a hypoxia-sensitive phenotype in subsequent analyses, confirming the proteomic findings.</p> <p>Conclusions</p> <p>Taken together, our data suggest that altered protein expression, structural protein remodeling, and the reduction of translation might play important roles in the early response to oxygen deprivation in <it>C. elegans</it>, and this information will help broaden our knowledge on the mechanism of hypoxia response.</p

Correlation of APE1 with VEGFA and CD163+ macrophage infiltration in bladder cancer and their prognostic significance

The present study sought to estimate the applicability of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1), vascular endothelial growth factor A (VEGFA) expression and CD163+ tumor‑associated macrophage (TAM) ratio as prognostic factors in bladder cancer (BCa). A total of 127 patients with bladder urothelial cancer who underwent radical cystectomy at Daping Hospital were recruited between January 2013 and January 2017, including 45 cases of non‑muscle invasive BCa (NMIBC) and 82 of MIBC. Immunohistochemical detection of APE1, VEGFA and CD163, as well as multiple immunofluorescence staining for APE1, VEGFA, CD163 and CD34, were performed on tissue samples. For APE1 and VEGFA, the staining was graded based on intensity (0‑3), while CD163 was graded (0‑3) based on the percentage of positively stained cells. The prognostic value of APE1, VEGF and CD163 was assessed using Kaplan‑Meier and Cox regression analysis. The results suggested that in BCa, high APE1 expression was associated with high VEGFA expression and more infiltration of CD163+ TAM. Furthermore, high expression of APE1 was associated with lymphovascular invasion of BCa, as well as reduced survival time. This indicates that APE1 may be associated with CD163+ TAM infiltration in BCa, with VEGFA as a possible influencing factor

EFFECTS OF SURFACE GROOVE ON SEPARATED FLOW TRANSITION ON A HIGH-LIFT LOW- PRESSURE TURBINE PROFILE UNDER STEADY INFLOW CONDITIONS

ABSTRACT LES (Large-Eddy Simulation) computations for a high-lift low-pressure turbine profile equipped with the span-wise groove on the suction surface are done to investigate the mechanism of the surface groove for separated flow transition control under steady inflow conditions, employing the dynamic Smagorinsky model. In addition to the baseline case (no groove), three groove positions which depend on the relative position of the groove trailing edge and the separation point on the suction surface are considered at two Reynolds numbers (Re, based on the inlet velocity and axial chord length). The results show that all grooves can reduce the calculated loss for Re=50000, due to the further upstream transition inception in the separated shear layer

Predicting Hepatotoxicity Associated with Low-Dose Methotrexate Using Machine Learning

An accurate prediction of the hepatotoxicity associated with low-dose methotrexate can provide evidence for a reasonable treatment choice. This study aimed to develop a machine learning-based prediction model to predict hepatotoxicity associated with low-dose methotrexate and explore the associated risk factors. Eligible patients with immune system disorders, who received low-dose methotrexate at West China Hospital between 1 January 2018, and 31 December 2019, were enrolled. A retrospective review of the included patients was conducted. Risk factors were selected from multiple patient characteristics, including demographics, admissions, and treatments. Eight algorithms, including eXtreme Gradient Boosting (XGBoost), AdaBoost, CatBoost, Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LightGBM), Tree-based Pipeline Optimization Tool (TPOT), Random Forest (RF), and Artificial Neural Network (ANN), were used to establish the prediction model. A total of 782 patients were included, and hepatotoxicity was detected in 35.68% (279/782) of the patients. The Random Forest model with the best predictive capacity was chosen to establish the prediction model (receiver operating characteristic curve 0.97, accuracy 64.33%, precision 50.00%, recall 32.14%, and F1 39.13%). Among the 15 risk factors, the highest score was a body mass index of 0.237, followed by age (0.198), the number of drugs (0.151), and the number of comorbidities (0.144). These factors demonstrated their importance in predicting hepatotoxicity associated with low-dose methotrexate. Using machine learning, this novel study established a predictive model for low-dose methotrexate-related hepatotoxicity. The model can improve medication safety in patients taking methotrexate in clinical practice

The role of carotenoid isomerase in maintenance of photosynthetic oxygen evolution in rice plant

Carotenoid isomerase (CRTISO) has been suggested to protect photosystem II (PS II) from photodamage, probably through its product lutein. However, the mechanism of the photoprotection still remains to be further elucidated. In this work, we cloned a point mutated gene reported to encode a CRTISO which is responsible for the accumulation of lutein in rice mutant zel1 by a mapbased cloning approach. The mutant phenotype was rescued by transformation with the corresponding gene of the wild type (WT). The activity of photosynthetic oxygen evolution was evidently suppressed in zel1. The amount of the core protein of PS II CP47 was much lower in all the PS II complexes especially in the LHCII-PS II supercomplexes and CP43-free PS II of zel1 than that of WT. On the other hand, the amount of another core protein of PS II CP43 of zel1 was decreased in the higher supercomplexes, whereas it was increased in the lower ones and PS II monomer. The immunodetection displayed that CP43, CP47, and the oxygen-evolving extrinsic proteins PsbO and PsbP were reduced, but the amount of reaction center protein D1 did not show significant change in zel1. Northern blot analysis showed that the transcriptional level of CP43 was down-regulated but not that of CP47 or D1 in zel1. In addition, the plastoquinone (PQ) Q A was in a reduced state in zel1. On the basis of the results, we suggest that CRTISO might function in regulating the transcription of CP43 and the translation of CP47 by affecting the redox state of the PQ to stabilize the extrinsic proteins of oxygen evolution complexes in the rice plant

NdhV subunit regulates the activity of type-1 NAD(P)H dehydrogenase under high light conditions in cyanobacterium Synechocystis sp PCC 6803

The cyanobacterial NAD(P)H dehydrogenase (NDH-1) complexes play crucial roles in variety of bioenergetic reactions. However, the regulative mechanism of NDH-1 under stressed conditions is still unclear. In this study, we detected that the NDH-1 activity is partially impaired, but the accumulation of NDH-1 complexes was little affected in the NdhV deleted mutant (Delta ndhV) at low light in cyanobacterium Synechocystis sp. PCC 6803. Delta ndhV grew normally at low light but slowly at high light under inorganic carbon limitation conditions (low pH or low CO2), meanwhile the activity of CO2 uptake was evidently lowered than wild type even at pH 8.0. The accumulation of NdhV in thylakoids strictly relies on the presence of the hydrophilic subcomplex of NDH-1. Furthermore, NdhV was co-located with hydrophilic subunits of NDH-1 loosely associated with the NDH-1L, NDH-1MS' and NDH-1M complexes. The level of the NdhV was significantly increased at high light and deletion of NdhV suppressed the up-regulation of NDH-1 activity, causing the lowered the photosynthetic oxygen evolution at pH 6.5 and high light. These data indicate that NdhV is an intrinsic subunit of hydrophilic subcomplex of NDH-1, required for efficient operation of cyclic electron transport around photosystem I and CO2 uptake at high lights