Early cartilage lesion and 5-year incident joint surgery in knee osteoarthritis patients: a retrospective cohort study.

OBJECTIVE: to investigate the association between cartilage lesion-related features observed in knee osteoarthritis (OA) patients' first MRI examination and incident knee surgery within 5 years. Additionally, to assess the predictive value of these features for the incident knee surgery. METHODS: We identified patients diagnosed with knee OA and treated at our institution between January 2015 and January 2018, and retrieved their baseline clinical data and first MRI examination films from the information system. Next, we proceeded to determine joint space narrowing grade, cartilage lesion size grade, cartilage full-thickness loss grade and cartilage lesion sum score for the medial and lateral compartments, respectively. Generalized linear regression models examined the association of these features with 5-year incident knee surgery. Positive and negative predictive values (PPVs and NPVs) were determined referring to 5-year incident knee surgery. RESULTS: Totally, 878 participants (knees) were found eligible to form the study population. Within the 5 years, surgery was performed on 61 knees. None of the cartilage-related features had been found significantly associated with incident surgery. The results were similar for medial and lateral compartments. The PPVs were low for all the features. CONCLUSIONS: Among symptomatic clinically diagnosed OA knees, cartilage lesions observed in the first MRI examinations were not found to be associated with the occurrence of joint surgery within a 5-year period. All these cartilage-related features appear to have no additional value in predicting 5-year incident joint surgery.

Using Sandwiched Silicon/Reduced Graphene Oxide Composites with Dual Hybridization for Their Stable Lithium Storage Properties.

Using silicon/reduced graphene oxide (Si/rGO) composites as lithium-ion battery (LIB) anodes can effectively buffer the volumetric expansion and shrinkage of Si. Herein, we designed and prepared Si/rGO-b with a sandwiched structure, formed by a duple combination of ammonia-modified silicon (m-Si) nanoparticles (NP) with graphene oxide (GO). In the first composite process of m-Si and GO, a core-shell structure of primal Si/rGO-b (p-Si/rGO-b) was formed. The amino groups on the m-Si surface can not only hybridize with the GO surface to fix the Si particles, but also form covalent chemical bonds with the remaining carboxyl groups of rGO to enhance the stability of the composite. During the electrochemical reaction, the oxygen on the m-Si surface reacts with lithium ions (Li+) to form Li2O, which is a component of the solid-electrolyte interphase (SEI) and is beneficial to buffering the volume expansion of Si. Then, the p-Si/rGO-b recombines with GO again to finally form a sandwiched structure of Si/rGO-b. Covalent chemical bonds are formed between the rGO layers to tightly fix the p-Si/rGO-b, and the conductive network formed by the reintroduced rGO improves the conductivity of the Si/rGO-b composite. When used as an electrode, the Si/rGO-b composite exhibits excellent cycling performance (operated stably for more than 800 cycles at a high-capacity retention rate of 82.4%) and a superior rate capability (300 mA h/g at 5 A/g). After cycling, tiny cracks formed in some areas of the electrode surface, with an expansion rate of only 27.4%. The duple combination of rGO and the unique sandwiched structure presented here demonstrate great effectiveness in improving the electrochemical performance of alloy-type anodes.

Scalable Production of 2D Non-Layered Metal Oxides through Metal-Organic Gel Rapid Redox Transformation.

Two-dimensional (2D) nonlayered metal compounds with porous structure show broad application prospects in electrochemistry-related fields due to their abundant active sites, open ions/electrons diffusion channels, and faradaic reactions. However, scalable and universal synthesis of 2D porous compounds still remains challenging. Here, inspired by blowing gum, a metal-organic gel (MOG) rapid redox transformation (MRRT) strategy is proposed for the mass production of a wide variety of 2D porous metal oxides. Adequate crosslinking degree of MOG precursor and its rapid redox with NO3 - are critical for generating gas pressure from interior to exterior, thus blowing the MOG into 2D carbon nanosheets, which further act as self-sacrifice template for formation of oxides with porous and ultrathin structure. The versatility of this strategy is demonstrated by the fabrication of 39 metal oxides, including 10 transition metal oxides, one II-main group oxide, two III-main group oxides, 22 perovskite oxides, four high-entropy oxides. As an illustrative verification, the 2D transition metal oxides exhibit excellent capacitive deionization (CDI) performance. Moreover, the assembled CDI cell could act as desalting battery to supply electrical energy during electrode regeneration. This MRRT strategy offers opportunities for achieving universal synthesis of 2D porous oxides with nonlayered structures and studying their electrochemistry-related applications.

A New Structure with Localized sp2 Bonding for Fivefold Twinning in Diamond.

Changes in atomic bonding configuration in carbon from sp3 to sp2 are known to exist in certain structural defects in diamond, such as twin boundaries, grain boundaries, and dislocations, which have a significant impact on many properties of diamond. In this work, the atomic structure of fivefold twinning in detonation synthesized ultra-dispersed diamonds is investigated using a combination of techniques, including spherical aberration-corrected high-resolution electron microscopy (HREM), HREM image simulations, and molecular mechanics (MM) calculations. The experimental HREM images reveal clearly that the fivefold twinning in diamond has two distinct structures. In addition to the concentric fivefold twins, where the core structure is the intersection of five {111} twinning boundaries, a new extended core structure with co-hybridization of bonding is identified and analyzed in fivefold twinning. The atomic structure forming these fivefold twinning boundaries and their respective core structures is proposed to involve both the tetrahedral sp3 and planar graphitic sp2 bonding configurations, in which a co-hybridized planar hexagon of carbon serves as a fundamental structural unit. The presence of this sp2 -bonded planar unit of hexagonal carbon rings in general grain boundaries is also discussed.

Receptor-like protein kinase BAK1 promotes K+ uptake by regulating H+-ATPase AHA2 under low potassium stress.

Potassium (K+) is one of the essential macronutrients for plant growth and development. However, the available K+ concentration in soil is relatively low. Plant roots can perceive low K+ (LK) stress, then enhance high-affinity K+ uptake by activating H+-ATPases in root cells, but the mechanisms are still unclear. Here, we identified the receptor-like protein kinase Brassinosteroid Insensitive 1-Associated Receptor Kinase 1 (BAK1) that is involved in LK response by regulating the Arabidopsis (Arabidopsis thaliana) plasma membrane H+-ATPase isoform 2 (AHA2). The bak1 mutant showed leaf chlorosis phenotype and reduced K+ content under LK conditions, which was due to the decline of K+ uptake capacity. BAK1 could directly interact with the AHA2 C terminus and phosphorylate T858 and T881, by which the H+ pump activity of AHA2 was enhanced. The bak1 aha2 double mutant also displayed a leaf chlorosis phenotype that was similar to their single mutants. The constitutively activated form AHA2Δ98 and phosphorylation-mimic form AHA2T858D or AHA2T881D could complement the LK sensitive phenotypes of both aha2 and bak1 mutants. Together, our data demonstrate that BAK1 phosphorylates AHA2 and enhances its activity, which subsequently promotes K+ uptake under LK conditions.

The Transcription Factor MYB59 Regulates K+/NO3 - Translocation in the Arabidopsis Response to Low K+ Stress.

Potassium and nitrogen are essential nutrients for plant growth and development. Plants can sense potassium nitrate (K+/NO3 -) levels in soils, and accordingly they adjust root-to-shoot K+/NO3 - transport to balance the distribution of these ions between roots and shoots. In this study, we show that the transcription factorMYB59 maintains this balance by regulating the transcription of the Arabidopsis (Arabidopsis thaliana) Nitrate Transporter1.5 (NRT1.5)/ Nitrate Transporter/Peptide Transporter Family7.3 (NPF7.3) in response to low K+ (LK) stress. The myb59 mutant showed a yellow-shoot sensitive phenotype when grown on LK medium. Both the transcript and protein levels of NPF7.3 were remarkably reduced in the myb59 mutant. LK stress repressed transcript levels of both MYB59 and NPF7.3 The npf7.3 and myb59 mutants, as well as the npf7.3 myb59 double mutant, showed similar LK-sensitive phenotypes. Ion content analyses indicated that root-to-shoot K+/NO3 - transport was significantly reduced in these mutants under LK conditions. Moreover, chromatin immunoprecipitation and electrophoresis mobility shift assay assays confirmed that MYB59 bound directly to the NPF7.3 promoter. Expression of NPF7.3 in root vasculature driven by the PHOSPHATE 1 promoter rescued the sensitive phenotype of both npf7.3 and myb59 mutants. Together, these data demonstrate that MYB59 responds to LK stress and directs root-to-shoot K+/NO3 - transport by regulating the expression of NPF7.3 in Arabidopsis roots.

A novel analytic approach for outcome prediction in diffuse large B-cell lymphoma by [18F]FDG PET/CT.

PURPOSE: This study aimed to develop a novel analytic approach based on 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) radiomic signature (RS) and International Prognostic Index (IPI) to predict the progression-free survival (PFS) and overall survival (OS) of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: We retrospectively enrolled 152 DLBCL patients and divided them into a training cohort (n = 100) and a validation cohort (n = 52). A total of 1245 radiomic features were extracted from the total metabolic tumor volume (TMTV) and the metabolic bulk volume (MBV) of pre-treatment PET/CT images. The least absolute shrinkage and selection operator (LASSO) algorithm was applied to develop the RS. Cox regression analysis was used to construct hybrid nomograms based on different RS and clinical variables. The performances of hybrid nomograms were evaluated using the time-dependent receiver operator characteristic (ROC) curve and the Hosmer-Lemeshow test. The clinical utilities of prediction nomograms were determined via decision curve analysis. The predictive efficiency of different RS, clinical variables, and hybrid nomograms was compared. RESULTS: The RS and IPI were identified as independent predictors of PFS and OS, and were selected to construct hybrid nomograms. Both TMTV- and MBV-based hybrid nomograms had significantly higher values of area under the curve (AUC) than IPI in training and validation cohorts (all P < 0.05), while no significant difference was found between TMTV- and MBV-based hybrid nomograms (P > 0.05). The Hosmer-Lemeshow test showed that both TMTV- and MBV-based hybrid nomograms calibrated well in the training and validation cohorts (all P > 0.05). Decision curve analysis indicated that hybrid nomograms had higher net benefits than IPI. CONCLUSION: The hybrid nomograms combining RS with IPI could significantly improve survival prediction in DLBCL. Radiomic analysis on MBV may serve as a potential approach for prognosis assessment in DLBCL. TRIAL REGISTRATION: NCT04317313. Registered March 16, 2020. Public site: https://clinicaltrials.gov/ct2/show/NCT04317313.

Improved catalytic performance of carrier-free immobilized lipase by advanced cross-linked enzyme aggregates technology.

The cross-linked enzyme aggregates (CLEAs) are one of the technologies that quickly immobilize the enzyme without a carrier. In this study, ionic liquid with amino group (1-aminopropyl-3-methylimidazole bromide, FIL) was used as the novel functional surface molecule to modify CRL (Candida rugosa lipase, CRL). The enzymatic properties of CRL-FIL-CLEAs were investigated. The activity of CRL-FIL-CLEAs (5.51 U/mg protein) was 1.9 times higher than that of CRL-CLEAs (2.86 U/mg protein) without surface modification. After incubating in a centrifuge tube for 50 min at 60 °C, CRL-FIL-CLEAs still maintained 61% of its initial activity, while the value for CRL-CLEAs was only 22%. After repeated use for five times, compared with the 22% residual activity of CRL-CLEAs, the value of CRL-FIL-CLEAs was 51%. Based on the above results, it was indicated that this method provided a new idea for the effective synthesis of immobilized enzyme.

A deep learning framework for 18F-FDG PET imaging diagnosis in pediatric patients with temporal lobe epilepsy.

PURPOSE: Epilepsy is one of the most disabling neurological disorders, which affects all age groups and often results in severe consequences. Since misdiagnoses are common, many pediatric patients fail to receive the correct treatment. Recently, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging has been used for the evaluation of pediatric epilepsy. However, the epileptic focus is very difficult to be identified by visual assessment since it may present either hypo- or hyper-metabolic abnormality with unclear boundary. This study aimed to develop a novel symmetricity-driven deep learning framework of PET imaging for the identification of epileptic foci in pediatric patients with temporal lobe epilepsy (TLE). METHODS: We retrospectively included 201 pediatric patients with TLE and 24 age-matched controls who underwent 18F-FDG PET-CT studies. 18F-FDG PET images were quantitatively investigated using 386 symmetricity features, and a pair-of-cube (PoC)-based Siamese convolutional neural network (CNN) was proposed for precise localization of epileptic focus, and then metabolic abnormality level of the predicted focus was calculated automatically by asymmetric index (AI). Performances of the proposed framework were compared with visual assessment, statistical parametric mapping (SPM) software, and Jensen-Shannon divergence-based logistic regression (JS-LR) analysis. RESULTS: The proposed deep learning framework could detect the epileptic foci accurately with the dice coefficient of 0.51, which was significantly higher than that of SPM (0.24, P < 0.01) and significantly (or marginally) higher than that of visual assessment (0.31-0.44, P = 0.005-0.27). The area under the curve (AUC) of the PoC classification was higher than that of the JS-LR (0.93 vs. 0.72). The metabolic level detection accuracy of the proposed method was significantly higher than that of visual assessment blinded or unblinded to clinical information (90% vs. 56% or 68%, P < 0.01). CONCLUSION: The proposed deep learning framework for 18F-FDG PET imaging could identify epileptic foci accurately and efficiently, which might be applied as a computer-assisted approach for the future diagnosis of epilepsy patients. TRIAL REGISTRATION: NCT04169581. Registered November 13, 2019 Public site: https://clinicaltrials.gov/ct2/show/NCT04169581.

SNHG5 protects chondrocytes in interleukin-1ß-stimulated osteoarthritis via regulating miR-181a-5p/TGFBR3 axis.

Long noncoding RNAs (lncRNAs) have been considered as important modulators in the development of osteoarthritis. The present study investigates whether there is a link between lncRNA small nucleolar RNA host gene 5 (SNHG5) and osteoarthritis pathogenesis, and the underlying molecular mechanism. To establish an in vitro model of osteoarthritis, interleukin 1ß (IL-1ß) was used to treat chondrocytes (C20/A4 cells) for mimicking the inflammatory condition in osteoarthritis pathogenesis. SNHG5 and miR-181a-5p expression levels were then detected in cartilage tissues of osteoarthritis patients and C20/A4 cells by quantitative polymerase chain reaction (qPCR). Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were applied for detecting the viability of chondrocytes, and the apoptosis of chondrocytes was examined through caspase-3 activity assay and flow cytometry analysis. Western blot and qPCR were employed for determining the expression levels of TGFBR3, ADAMTS5, and MMP-13. The regulatory relationships among SNHG5, miR-181a-5p, and TGFBR3 were verified by RNA immunoprecipitation and dual-luciferase reporter assays. The expression levels of SNHG5 and TGFBR3 were markedly decreased, and miR-181a-5p expression was enhanced in osteoarthritis tissues and chondrocytes treated with IL-1ß. SNHG5 knockdown inhibited the viability of chondrocytes, induced apoptosis, and promoted the expression levels of ADAMTS5 and MMP-13. Conversely, SNHG5 overexpression could counteract the effects of IL-1ß, increase the viability of chondrocytes and suppress apoptosis. Mechanically, SNHG5 positively regulated TGFBR3 expression via sponging miR-181a-5p. Moreover, miR-181a-5p overexpression and TGFBR3 knockdown counteracted the effects of SNHG5 on chondrocytes. SNHG5 can probably protect chondrocytes from the inflammatory response and reduce the degradation of the extracellular matrix via modulating the miR-181a-5p/TGFBR3 axis.

Single-Cell Isotope Dilution Analysis with LA-ICP-MS: A New Approach for Quantification of Nanoparticles in Single Cells.

Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) is an emerging method for the analysis of metal nanoparticles (NPs) in single cells. However, two main obstacles, low analytical throughput and lack of commercial reference materials, need to be overcome. In this work, we demonstrated the principles of a new approach termed "single-cell isotope dilution analysis" (SCIDA) to remove the two obstacles. For a proof of concept, macrophage cells were chosen as a model to study the uptake of silver NPs (AgNPs) at a single-cell level. Single cells exposed to AgNPs were placed in an array by a microfluidic technique; each cell in the array was precisely dispensed with a known picoliter droplet of an enriched isotope solution with a commercial inkjet printer; accurate quantification of AgNPs in single cells was done by using isotope dilution LA-ICP-MS. The average Ag mass of 1100 single cells, 396 ± 219 fg Ag per cell, was in good accord with the average of the population of cells determined by solution ICP-MS analysis. The detection limit was 0.2 fg Ag per cell. The SCIDA approach is expected to be widely applied for the study of cell-NP interactions and biological effects of NPs at the single-cell level.

[Effects of Xiangdan Injection on pharmacokinetics and pharmacodynamics of warfarin in rats in vivo].

This study is to explore the effect of Xiangdan Injection on anticoagulation of warfarin in rats. Rats were randomly divided into different groups and then administered, subsequently the blood samples were collected at a set series of time points to measure PT(prothrombin time) and APTT(activated partial thromboplastin time) values, and INR(international normalized ratio) value was calculated. The plasma concentrations of warfarin enantiomers were determined by UPLC-MS/MS technology, and pharmacokinetic parameters were calculated by DAS 2.0 software. Statistical analysis was performed to compare differences between the groups. Single-dose study of warfarin showed that Xiangdan Injection alone had no effects on PT, APTT and INR, but when co-administrated with warfarin, PT and INR values were increased(P<0.01), while APTT was unaffected; after co-administration of the two drugs, C_(max), AUC_(0-t), and AUC_(0-∞) of S-warfarin increased(P<0.01), and t_(1/2) prolonged(P<0.01), while the pharmacokinetic parameters of R-warfarin were not changed significantly. Steady-state study of warfarin showed that after co-administration of the two drugs, the PT and INR values increased(P<0.05), and the plasma concentration of S-warfarin increased(P<0.01), while the plasma concentration of R-warfarin was not changed significantly. The results suggest that Xiangdan Injection itself has no effect on coagulation index, but can enhance the anticoagulant effect of warfarin by slowing metabolism of S-warfarin.

Genome-wide identification, phylogeny, and expression analysis of Sec14-like PITP gene family in sugarcane.

KEY MESSAGE: Six Sec14-like PITP genes from sugarcane were identified, two of them were cloned, and their biological functions were characterized indicating their involvement in plant defense against biotic and abiotic stresses. Sec14, a phosphatidylinositol transfer protein (PITP) is widely present in eukaryotes. In this study, the structure and expression patterns of six Sec14-like PITP genes (ScSEC14-1, ScSEC14p, ScSFH1, ScSFH2, ScPATL1, and ScPATL2) from sugarcane were analyzed, and two of them (ScSEC14-1 and ScSEC14p) were cloned and functionally verified. Phylogenetic analysis divided these genes into four groups, including group I (ScSFH1 and ScSFH2), group II (ScPATL1 and ScPATL2), Group III (ScSEC14p), and group V (ScSEC14-1). qRT-PCR analysis showed tissue-specific expression of these genes, primarily in the root, leaf, and bud tissues. They responded differently to SA, MeJA, and ABA stresses. ScSEC14-1, ScSEC14p, and ScSFH2 were upregulated by CuCl2 and CdCl2, while ScSEC14-1, ScSFH1, ScSFH2, and ScPATL1 were upregulated by PEG and NaCl. When infected by Sporisorium scitamineum, the transcripts of ScSFH1, ScSFH2, ScPATL1, and ScPATL2 were upregulated in the resistant genotype Yacheng 05-179, while those of ScSEC14-1 and ScSEC14p were upregulated in the susceptible genotype ROC22. Subcellular localization showed that ScSEC14-1 and ScSEC14p were mainly localized in the plasma membrane and cytoplasm. Enhanced growth of Escherichia coli BL21 cells expressing ScSEC14-1 and ScSEC14p showed high tolerance to NaCl and mannitol stresses. The transient overexpression of ScSEC14-1 and ScSEC14p in Nicotiana benthamiana leaves enhanced its resistance to the infection of tobacco pathogens Ralstonia solanacearum and Fusarium solani var. coeruleum. We can conclude the involvement of ScSEC14-1 and ScSEC14p in the defense against biotic and abiotic stresses, which should facilitate further research on Sec14-like PITP gene family, especially its regulatory mechanisms in sugarcane.

Treatment Outcome of Acute Sacral Nerve Stimulation in Functional Anorectal Pain.

BACKGROUND: Sacral nerve stimulation (SNS) has revolutionized the management of certain intractable cases of fecal and urinary incontinence; however, the management of functional anorectal pain (FAP) has been addressed in only a few studies. OBJECTIVE: The aim of this study was to evaluate the treatment effect of SNS in improving FAP symptoms. METHODS: A total of 120 patients with FAP who had undergone temporary SNS probe placement were investigated at Qianfoshan Hospital between January 2014 and December 2016. Pre- and post-SNS treatment outcomes were assessed using the VAS, anorectal manometry, and the 36-item short-form health survey (SF-36) medical outcomes study instrument. RESULTS: A total of 120 patients proceeded to insertion of an SNS probe at the S3 nerve root (2 Hz, 1.50 mA, 0.10 milliseconds). Of these, 75 patients were cured, 41 improved, and 4 had an ineffective outcome. The total effectiveness rate was 96.7% 1 year after treatment. There was a significant reduction in the median VAS score pre-SNS and post-SNS, from 8 to 3, respectively. Patients post-SNS had lower anal maximum contraction pressure and anal rest pressure than did patients pre-SNS. Compared with the pretreatment group, there were no substantial differences between anal longest contraction time and rectal rest pressure. In addition to general health, there was a substantial improvement in the remaining dimension scores of the SF-36. CONCLUSION: The effect of SNS in treating FAP was positive, and the improvement of symptoms was substantial and worthy of clinical promotion.

SMAC: Spatial multi-category angle-based classifier for high-dimensional neuroimaging data.

With the development of advanced imaging techniques, scientists are interested in identifying imaging biomarkers that are related to different subtypes or transitional stages of various cancers, neuropsychiatric diseases, and neurodegenerative diseases, among many others. In this paper, we propose a novel spatial multi-category angle-based classifier (SMAC) for the efficient identification of such imaging biomarkers. The proposed SMAC not only utilizes the spatial structure of high-dimensional imaging data but also handles both binary and multi-category classification problems. We introduce an efficient algorithm based on an alternative direction method of multipliers to solve the large-scale optimization problem for SMAC. Both our simulation and real data experiments demonstrate the usefulness of SMAC.

A study on the clinical characteristics of treating nevus of Ota by Q-switched Nd:YAG laser.

The purpose of this study was to retrospectively analyze the clinical characteristics of treating nevus of Ota by Q-switched Nd:YAG laser in Laser Cosmetology Center of Department of Dermatology, the Second Hospital, Xi'an Jiaotong University. The data of 1168 patients of nevus of Ota were analyzed retrospectively, which included the correlation among lesion color, treatment sessions, sex, age, lesion types, and effect. The Q-switched (QS) Nd:YAG laser system had a higher number of treatment sessions which were positively associated with a better response to treatment. Other variables, including gender, age, the categorization of the lesion according to Tanino's classification, and the color of the lesion, were not associated with the response to treatment. The treatment of nevus of Ota with QS Nd:YAG laser is safe and effective, with rare complications.

AtKC1 and CIPK23 Synergistically Modulate AKT1-Mediated Low-Potassium Stress Responses in Arabidopsis.

In Arabidopsis (Arabidopsis thaliana), the Shaker K(+) channel AKT1 conducts K(+) uptake in root cells, and its activity is regulated by CBL1/9-CIPK23 complexes as well as by the AtKC1 channel subunit. CIPK23 and AtKC1 are both involved in the AKT1-mediated low-K(+) (LK) response; however, the relationship between them remains unclear. In this study, we screened suppressors of low-K(+) sensitive [lks1 (cipk23)] and isolated the suppressor of lks1 (sls1) mutant, which suppressed the leaf chlorosis phenotype of lks1 under LK conditions. Map-based cloning revealed a point mutation in AtKC1 of sls1 that led to an amino acid substitution (G322D) in the S6 region of AtKC1. The G322D substitution generated a gain-of-function mutation, AtKC1(D), that enhanced K(+) uptake capacity and LK tolerance in Arabidopsis. Structural prediction suggested that glycine-322 is highly conserved in K(+) channels and may function as the gating hinge of plant Shaker K(+) channels. Electrophysiological analyses revealed that, compared with wild-type AtKC1, AtKC1(D) showed enhanced inhibition of AKT1 activity and strongly reduced K(+) leakage through AKT1 under LK conditions. In addition, phenotype analysis revealed distinct phenotypes of lks1 and atkc1 mutants in different LK assays, but the lks1 atkc1 double mutant always showed a LK-sensitive phenotype similar to that of akt1 This study revealed a link between CIPK-mediated activation and AtKC1-mediated modification in AKT1 regulation. CIPK23 and AtKC1 exhibit distinct effects; however, they act synergistically and balance K(+) uptake/leakage to modulate AKT1-mediated LK responses in Arabidopsis.

Ginkgolide A inhibits lipopolysaccharide-induced inflammatory response in human coronary artery endothelial cells via downregulation of TLR4-NF-κB signaling through PI3K/Akt pathway.

Ginkgolide A (GA) is a one of the active components of Ginkgo biloba. We aimed to detect the effects GA on the lipopolysaccharide (LPS)-induced inflammatory response in human coronary artery endothelial cells (HCAECs) and whether the effects are associated with the inhibition of toll-like receptor 4 (TLR4)-NF-κB signaling through PI3K/Akt pathway. HCAECs were stimulated with LPS and treated with GA or TLR4 inhibitor CLI-095. A PI3K/Akt inhibitor LY294002 was used to block the PI3K/Akt pathway. The toxic effects of GA, LPS and LY294002 on HCAEC were evaluated using MTT assay. Levels inflammatory mediators, TLR4 mRNA, NF-κB signaling activity were valuated. We found LPS stimulation significantly increased the release of IL-6, IL-8, MCP-1 and TNF-α from HCAECs, elevated the TLR4 mRNA expression and activated the NF-κB signaling. GA and CLI-095 abolished the LPS-induced inflammatory mediator release and NF-κB signaling activation, and GA reduced the TLR4 mRNA expression without affecting cell viability. However, PI3K/Akt blocking abolished the effects of GA on HCAECs. We conclude that GA could attenuate the LPS-induced inflammatory response in HCAECs and the anti-inflammatory activity might be associated with the inhibition of TLR4-NF-κB signaling through PI3K/AKT pathway. These findings suggest a therapeutic potential of GA in endothelial inflammation.

Increased PTOV1 expression is related to poor prognosis in epithelial ovarian cancer.

Altered expression of prostate tumor overexpressed-1 (PTOV1) is observed in various types of human cancers. However, the role of PTOV1 in epithelial ovarian cancer (EOC) remains unclear. PTOV1 messenger (m)RNA expression in EOC patients was evaluated by quantitative real-time PCR (qRT-PCR). PTOV1 protein expression was also analyzed in archived paraffin-embedded EOC tissues using immunohistochemistry (IHC), and its association with overall survival of patients was analyzed by statistical analysis. Results from qRT-PCR analysis show that the expression level of PTOV1 mRNA was significantly higher in tumor tissues of EOC, compared to that in adjacent noncancerous tissues (P < 0.001). IHC staining showed that high expression of PTOV1 was detected in 57.2 % (87/152) of EOC cases. High expression of PTOV1 was significantly associated with pathological grade (P = 0.029) and clinical stage (P = 0.001). Moreover, the results of Kaplan-Meier analysis indicated that a high expression level of PTOV1 resulted in a significantly poor prognosis of EOC patients. Multivariate analysis showed that high expression of PTOV1 was an independent prognostic factor for overall survival (P < 0.001). In conclusion, PTOV1 protein abnormal expression might contribute to the malignant progression of EOC. High expression of PTOV1 predicts poor prognosis in patients with EOC.