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Objective. To investigate the roles and possible mechanisms of SIRT2 and KLF4 in the development and progression of myeloma. Methods. Rt-PCR was used to detect SIRT2 in myeloma samples from patients and myeloma cells, the expression level of KLF4 in myeloma cells, and the effect of downregulation of SIRT2 expression on KLF4 expression level. MTT assay and wound-healing assay were used to observe the proliferation and migration of U266cells transient transfected with Sirt2 inhibitors. Results. SIRT2 is highly expressed in myeloma, but KLF4 was down. Downregulation of SIRT2 expression stimulated the expression level of KLF4. Reduced SIRT2 activity results in the release of KLF4 expression, which inhibits the proliferation and migration of myeloma cells. Conclusion. SIRT2-KLF4 combination plays an important role in the occurrence and development of myeloma. [ABSTRACT FROM AUTHOR]

Objective. To investigate the role of nestin in regulating Keap1-nuclear factor erythroid-2-related factor 2 (Nrf2)-heme oxygenase-1-(HO-1-) mediated antioxidant responses in stress and malignant hematopoiesis. Methods. The mRNA of peripheral blood mononuclear cells was extracted from 20 leukemia patients and 20 healthy people who were hospitalized in the Hematology Department of our hospital from September 2020 to December 2021, and the mRNA levels of nestin, Keap1, Nrf2, and HO-1 were detected by real-time- (RT-) PCR. Results. Compared with healthy controls, the mRNA of nestin, Keap1, Nrf2, and HO-1 in peripheral blood mononuclear cells of leukemia patients was significantly upregulated. Conclusion. The occurrence and development of leukemia are closely related to nestin regulating Keap1-Nrf2-Ho-1 signal pathway. Research Significance. This study determined the effect of nestin on the biological behavior of leukemia cells and its possible mechanism and confirmed that nestin may be a marker of tumor and tumor blood vessels. [ABSTRACT FROM AUTHOR]

To establish methods for simultaneous determination of isoquercitrin, astragalin in leaves, quercetin, and kaempferol in flowers of Lysimachia clethroides Duby, respectively, the methods were ultrasound-assisted extraction combined with RP-HPLC, and ionic liquid was used as the extraction solvent. Meanwhile, the antioxidant activity of the different extracts of L. clethroides was evaluated. Purospher STAR RP-C18 column (4.6 mm × 250 mm, 5 μm) was used for analysis. The flow rate was 0.6 mL·min−1, and the column temperature was 25°C. The detection wavelength was 360 nm. The mobile phases a and b consisted of acetonitrile-0.4% phosphoric acid (18 : 82, v/v), methanol (A), and 0.4% phosphoric acid (B), respectively. Linear ranges were 0.068~1.64, 0.060~1.44, 0.0080~0.19, and 0.0077~0.18 μg for isoquercitrin, astragalin, quercetin, and kaempferol, respectively. The average recoveries of the four constituents were 99.17%, 98.39%, 100.68%, and 98.81%, respectively. The antioxidant activity of the extracts was detected by DPPH, ABTS, and FRAP. Under the optimized conditions, all the test solutions showed a certain antioxidant activity and the ionic liquid extracts were better than that of extract of methanol. Ionic liquid used as the extraction solvent had the potential to extract active ingredients efficiently from L. clethroides, and this method improved the antioxidant activity with accurate and reliable results. [ABSTRACT FROM AUTHOR]

We report a rare case of advanced metastatic renal cell carcinoma which initially presented to the clinic with back and forehead lumps. Ultrasound imaging of the lumps and later of the abdomen picked up a right renal tumour which led to further computed tomography and bone scans. The bone scan confirmed that the forehead lump was a calvarial metastasis and such a presentation for metastatic RCC is very rare which bears a significantly poorer prognosis. [ABSTRACT FROM AUTHOR]

As the fifth most common cancer in men and the eighth most common cancer in women, hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide, with standard chemotherapy and radiation being minimally effective in prolonging survival. Virus hepatitis, particularly HBV and HCV infection is the most prominent risk factor for HCC development. Mammalian target of rapamycin (mTOR) pathway is activated in viral hepatitis and HCC. mTOR inhibitors have been tested successfully in clinical trials for their antineoplastic potency and well tolerability. Treatment with mTOR inhibitor alone or in combination with cytotoxic drugs or targeted therapy drug scan significantly reduces HCC growth and improves clinical outcome, indicating that mTOR inhibition is a promising strategy for the clinical management of HC. [ABSTRACT FROM AUTHOR]

The multiple satellites mission planning is a complex combination optimization problem. A knowledge-based simulated annealing algorithm is proposed to the multiple satellites mission planning problems. The experimental results suggest that the proposed algorithm is effective to the given problem. The knowledge-based simulated annealing method will provide a useful reference for the improvement of existing optimization approaches. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) can induce intestinal inflammatory response and mucosal injury. Antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown in our previous studies to prevent oxidative stress and inflammatory response in gut after TBI. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), an Nrf2 inducer, can protect against TBI-induced intestinal inflammatory response andmucosal injury in mice. Adult male ICR mice were randomly divided into three groups: (1) sham + vehicle group, (2) TBI + vehicle group, and (3) TBI + tBHQ group (n = 12 per group). Closed head injury was adopted using Hall's weight-dropping method. Intestinal mucosa apoptosis and inflammatory- related factors, such as nuclear factor kappa B (NF-κB), tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1), were investigated at 24 h after TBI. As a result, we found that oral treatment with 1% tBHQ prior to TBI for one week markedly decreased NF-κB activation, inflammatory cytokines production, and ICAM-1 expression in the gut. Administration of tBHQ also significantly attenuated TBI-induced intestinalmucosal apoptosis. The results of the present study suggest that tBHQ administration could suppress the intestinal inflammation and reduce the mucosal damage following TBI. [ABSTRACT FROM AUTHOR]

Inflammatory response plays an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that plays a crucial role in cytoprotection against inflammation. The present study investigated the role of Nrf2 in the cerebral upregulation of NF-κB activity, proinflammatory cytokine, and ICAM-1 after TBI. Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact head injury. Electrophoretic mobility shift assays (EMSAs) were performed to analyze the activation of nuclear factor kappa B (NF-κB). Enzyme-linked immunosorbent assays were performed to quantify the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Immunohistochemistry staining experiments were performed to detect the expression of intercellular adhesion molecule-1 (ICAM- 1). Nrf2 (-/- ) mice were shown to have more NF-κB activation, inflammatory cytokines TNF-α, IL-1β and IL-6 production, and ICAM-1 expression in brain after TBI compared with their wild-type Nrf2 (+/+) counterparts. The results suggest that Nrf2 plays an important protective role in limiting the cerebral upregulation of NF-κB activity, proinflammatory cytokine, and ICAM-1 after TBI. [ABSTRACT FROM AUTHOR]

Inflammatory response plays an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that plays a crucial role in cytoprotection against inflammation. The present study investigated the role of Nrf2 in the cerebral upregulation of NF-κB activity, proinflammatory cytokine, and ICAM-1 after TBI. Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact head injury. Electrophoretic mobility shift assays (EMSAs) were performed to analyze the activation of nuclear factor kappa B (NF-κB). Enzyme-linked immunosorbent assays were performed to quantify the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Immunohistochemistry staining experiments were performed to detect the expression of intercellular adhesion molecule-1 (ICAM-1). Nrf2 (-/-)mice were shown to have more NF-κB activation, inflammatory cytokines TNF-α, IL-1β and IL-6 production, and ICAM-1 expression in brain after TBI compared with their wild-type Nrf2 (+/+) counterparts. The results suggest that Nrf2 plays an important protective role in limiting the cerebral upregulation of NF-κB activity, proinflammatory cytokine, and ICAM-1 after TBI. [ABSTRACT FROM AUTHOR]

The design of packaged and ESD protected RF front-end circuits for UHF receiver working at ISM band is presented. By extensively evaluating the effects of the package and ESD parasitics on the LNA input impedance, transconductance, and noise figure, some useful guidelines on the design of inductively degenerated common emitter LNA with package and ESD protection are provided. In addition, by taking advantage of both the bipolar and MOSFET devices, a BiFET mixer with low noise and high linearity is also described in this article. With the careful consideration of the tradeoffs among noise figure, linearity, power gain, and power consumption, the front-end is implemented in a generic low-cost 0.8-μm BiCMOS technology. The on-board measurement of the packaged RF front-end circuits demonstrates a 20.3-dB power gain, 2.6-dB DSB noise figure, and -9.5-dBm input referred third intercept point while consuming about 3.9-mA current. © 2007 Wiley Periodicals, Inc. Int J RF and Microwave CAE, 2007. [ABSTRACT FROM AUTHOR]

Aim. To investigate the role of Ca2+ release-activated Ca2+ (CRAC) channels in the ROS production in macrophages. Methods. The intracellular [Ca2+]i was analyzed by confocal laser microscopy. The production of ROS was assayed by flow cytometry. Results. Both LPS and thapsigargin induced an increase in intracellular [Ca2+]i, either in the presence or absence of extracellular Ca2+ in murine macrophages. The Ca2+ signal was sustained in the presence of external Ca2+ and only initiated a mild and transient rise in the absence of external Ca2+. CRAC channel inhibitor 2-APB completely suppressed the Ca2+ entry signal evoked by thapsigargin, and suppressed approximately 93% of the Ca2+ entry signal evoked by LPS. The increase in intracellular [Ca2+]i, was associated with increased ROS production, which was completely abolished in the absence of extracellular Ca2+ or in the presence of CRAC channel inhibitors 2-APB and Gd3+. The mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxy- phenylhydrazone and the inhibitor of the electron transport chain, antimycin, evoked a marked increase in ROS production and completely inhibited thapsigargin and LPS-evoked responses. Conclusions. These findings indicate that the LPS-induced intracellular [Ca2+]i increase depends on the Ca2+ entry through CRAC channels, and close functional coupling between CRAC and ROS production in murine macrophages. [ABSTRACT FROM AUTHOR]

Aim. To investigate the role of Ca2+ release-activated Ca2+ (CRAC) channels in the ROS production in macrophages. Methods. The intracellular [Ca2+]i was analyzed by confocal laser microscopy. The production of ROS was assayed by flow cytometry. Results. Both LPS and thapsigargin induced an increase in intracellular [Ca2+]i, either in the presence or absence of extracellular Ca2+ in murine macrophages. The Ca2+ signal was sustained in the presence of external Ca2+ and only initiated a mild and transient rise in the absence of external Ca2+. CRAC channel inhibitor 2-APB completely suppressed the Ca2+ entry signal evoked by thapsigargin, and suppressed approximately 93% of the Ca2+ entry signal evoked by LPS. The increase in intracellular [Ca2+]i was associated with increased ROS production, which was completely abolished in the absence of extracellular Ca2+ or in the presence of CRAC channel inhibitors 2-APB and Gd3+. The mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxy-phenylhydrazone and the inhibitor of the electron transport chain, antimycin, evoked a marked increase in ROS production and completely inhibited thapsigargin and LPS-evoked responses. Conclusions. These findings indicate that the LPS-induced intracellular [Ca2+]i increase depends on the Ca2+ entry through CRAC channels, and close functional coupling between CRAC and ROS production in murine macrophages. [ABSTRACT FROM AUTHOR]

Stroke is one of the fatal diseases worldwide, and its primary mechanism is produced by cerebrovascular stenosis, blockages, or embolisms. Computer-aided diagnosis can assist clinical practitioners in identifying cerebrovascular anomalies, elucidating the precise lesions' location in the patients, and providing guidance for clinical therapy. Due to different portions of the cerebrovascular possessing diverse morphological properties and the limited narrow area, the detection effect is unsatisfactory. A retrained two-stage algorithm for detecting cerebral arterial stenosis in CTA images is proposed to solve these problems by further fusing image features and improving the quality of regions of interest. In Faster R-CNN and Libra R-CNN, the backbone network was Resnet50, with deformable convolutional and nonlocal neural networks introduced in the third, fourth, and fifth stages of the backbone network. Deformable convolutional networks learned offsets to extract morphological features of blood vessels in different tomographic planes. Nonlocal neural networks fused global information and extracted global features from location information of feature maps. A cascade detector refined object classification and bounding box regression before prediction. The experimental results show that the retained algorithm increases mAP by 7.3% and 7.5%, respectively, compared with Faster R-CNN and Libra R-CNN. Deformable convolutional networks, nonlocal neural networks, and cascade detectors are incorporated into further feature fusion; thus, semantic information about the cerebrovascular structure is learned, demonstrating more accurate stenotic region detection and demonstrating generalizability across different two-stage algorithms. [ABSTRACT FROM AUTHOR]

Sugar price forecasting has attracted extensive attention from policymakers due to its significant impact on people's daily lives and markets. In this paper, we present a novel hybrid deep learning model that utilizes the merit of a time series decomposition technology empirical mode decomposition (EMD) and a hyperparameter optimization algorithm Tree of Parzen Estimators (TPEs) for sugar price forecasting. The effectiveness of the proposed model was implemented in a case study with the price of London Sugar Futures. Two experiments are conducted to verify the superiority of the EMD and TPE. Moreover, the specific effects of EMD and TPE are analyzed by the DM test and improvement percentage. Finally, empirical results demonstrate that the proposed hybrid model outperforms other models. [ABSTRACT FROM AUTHOR]

Under the background of economic globalization, supply chain is becoming more and more complex, which is manifested in the instability of external environment. On the one hand, with the improvement of global environmental protection awareness, the government's policy tools for environmental impact (carbon tax) on the whole supply chain have become one of the major external problems faced by the supply chain enterprises; on the other hand, the intensification of competition between upstream and downstream in supply chains makes supply disruption an important proposition to be solved urgently. In this paper, the two propositions of green and supply disruption are reduced to two factors affecting the cost. The average total cost function of the manufacturer as a recycler is established. The practicability of the algorithm and the effectiveness of the model are verified by Lingo, Particle Swarm Optimization, and Genetic Algorithm, with the purpose of obtaining the optimal strategies for manufacturers who play the role of the recycler in the closed-loop supply chain. [ABSTRACT FROM AUTHOR]

MicroRNAs play significant roles in the development of cancer and may serve as promising therapeutic targets. In our previous work, miR-219-5p was identified as one of the important metastasis-related microRNAs in HCC. Here we demonstrated that miR-219-5p expression was elevated in HCC tissues and was associated with vascular invasion and dismal prognosis. In multivariate analysis, miR-219-5p was identified as an independent prognostic indicator for HCC patients. Functional mechanism analyses showed that miR-219-5p promoted HCC cell proliferation and invasion in in vitro, as well as in vivo, tumor growth and metastasis in nude mice models bearing human HCC tumors. In addition, cadherin 1 (CDH1) was revealed to be a downstream target of miR-219-5p in HCC cells. In conclusion, miR-219-5p promotes tumor growth and metastasis of HCC by regulating CDH1 and can serve as a prognostic marker for HCC patients. [ABSTRACT FROM AUTHOR]

A novel hybrid region-based active contour model is presented to segment medical images with intensity inhomogeneity. The energy functional for the proposed model consists of three weighted terms: global term, local term, and regularization term. The total energy is incorporated into a level set formulation with a level set regularization term, from which a curve evolution equation is derived for energy minimization. Experiments on some synthetic and real images demonstrate that our model is more efficient compared with the localizing region-based active contours (LRBAC) method, proposed by Lankton, and more robust compared with the Chan-Vese (C-V) active contour model. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM) has been extensively applied as preferable herbal remedy for menopausal symptoms. In the present work, the potential of a TCM recipe named RRF, composed of Radix Astragali, Radix Angelicae Sinensis, and Folium Epimedii, was investigated on a natural aging rat model. After administration of RRF (141, 282, and 564mg/kg/d), the circulated estradiol (E2) level increased accompanied by a reduction of serum follicle stimulating hormone (FSH). But no significant impact on serum lutenizing hormone (LH) level was observed. As a result of the E2-FSH-LH adjustment, the histomorphology degenerations of ovary, uterus, and vagina of the 11.5-month female rats were alleviated. And lumbar vertebrae trabecular microstructure was also restored under RRF exposure by means of increasing the trabecular area and area rate. Moreover, levels of hypothalamic dopamine (DA) and norepinephrine (NE) rallied significantly after RRF treatment. Results from our studies suggest that RRF possesses a positive regulation on the estrogen imbalance and neurotransmitter disorder, there by restoring reproductive organ degeneration and skeleton deterioration. The above-mentioned benefits of RRF on the menopause syndromes recommend RRF as a potential candidate for the treatment of perimenopausal syndrome. [ABSTRACT FROM AUTHOR]

An amino acid, 3S-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid, was isolated for the first time from the leaves of Cichorium endivia. The complete assignment of its ¹H and 13C NMR spectroscopic data was carried out also for the first time based on extensive 1D and 2D NMR experiments. Cytotoxicity of this isolated compound against HCT-8 and HepG2 human cancer cell lines was evaluated for the first time, with moderate activities being found. [ABSTRACT FROM AUTHOR]

Background and Aim. Aberrant activationof theTGF-𝛽1/Smad pathway contributes to the activation of hepatic stellate cells (HSCs). MicroRNA-195 has been shown to regulate the activation of HSCs.Theaim of this study was to investigate the role of miRNA-195 in HSCs activation. Methods. A liver fibrotic ratmodel induced by diethylnitrosamine was established. Dual luciferase reporter assays were performed to verify that Smad7 was the target of miRNA-195.The expression levels of miR-195, Smad7, and 𝛼-SMAin HSC-T6 transfected, respectively, with miR-195 mimic, inhibitor, or control were measured by qRT-PCR. The protein expression of Smad7 was detected by Western blot analysis. Results. Enhanced miR-195 and decreased Smad7 were observed in diethylnitrosamineinduced liver fibrotic rats (𝑃 < 0.05). Dual luciferase reporter assays showed that the miR-195 mimic significantly suppressed the luciferase activity of a reporter plasmid carrying the binding site of miR-195 on the 3󸀠UTR of Smad7 (𝑃 < 0.05).ThemiR-195 mimics activated HSCs, further elevated miR-195 and 𝛼-SMA (𝑃 < 0.01), and reduced the Smad7 level (𝑃 < 0.05). The miR-195 inhibitors blocked the activation of HSCs, reduced the expression of miR-195 and 𝛼-SMA (𝑃 < 0.01), and upregulated the expression of Smad7 (𝑃 < 0.05). Conclusion. Collectively, we demonstrated that miRNA-195 activated HSCs by targeting Smad7. [ABSTRACT FROM AUTHOR]

A novel method, which is based on the triple-frequency combination and Space-Based Telemetry, Tracking, and Command (STT&C) stations, is proposed in this paper. Considering BeiDou Navigation Satellite System (BDS) Geostationary Orbit (GEO) and Inclined Geostationary Orbit (IGSO) satellites as the STT&C facilities, firstly, we presented the BDS Medium Earth Orbit (MEO) satellites’ precise orbit determination scheme based on triple-frequency combination. Then, we gave the sufficient and necessary conditions about the visibility and the coverage rate calculation model of STT&C to BDS MEO satellite. And then we deduced the model of BDS MEO satellites precise orbit determination based on triple-frequency combination observations. At last, we designed the simulation calculation. The simulation results show that orbit determination of BDS MEO satellite based on STT&C station can be realized at all times. And most of the simulation period time, under the condition of the dm level orbit determination for GEO/IGSO satellites, the position accuracy of the relative orbit determination is better than 4 m, the horizontal accuracy of the relative orbit determination is within 2.5 m, and the vertical accuracy of the relative orbit determination is less than 3.5 m. [ABSTRACT FROM AUTHOR]

The lipoxins are the first proresolution mediators to be recognized and described as the endogenous "braking signals" for inflammation. We evaluated the anti-inflammatory and proresolution bioactions of lipoxin A4 in our lipopolysaccharide (LPS-)induced lung injury model. We demonstrated that lipoxin A4 significantly improved histology of rat lungs and inhibited IL-6 and TNF-α in LPS-induced lung injury. In addition, lipoxin A4 increased alveolar fluid clearance (AFC) and the effect of lipoxin A4 on AFC was abolished by CFTRinh-172 (a specific inhibitor of CFTR).Moreover, lipoxin A4 could increase cystic fibrosis transmembrane conductance regulator (CFTR) protein expression in vitro and in vivo. In rat primary alveolar type II (ATII) cells, LPS decreased CFTR protein expression via activation of PI3K/Akt, and lipoxin A4 suppressed LPS-stimulated phosphorylation of Akt. These results showed that lipoxin A4 enhanced CFTR protein expression and increased AFC via PI3K/Akt pathway. Thus, lipoxin A4 may provide a potential therapeutic approach for acute lung injury. [ABSTRACT FROM AUTHOR]

Pathogenic mechanisms underlying the development of lung cancer are very complex and not yet entirely clarified. T lymphocytes and their immune-regulatory cytokines play a pivotal role in controlling tumor growth and metastasis. Following activation by unique cytokines, CD4+ T helper cells differentiate into Th1, Th2, Th17, and regulatory T cells (Tregs). Traditionally, research in lung cancer immunity has focused almost exclusively on Th1/Th2 cell balance. Recently, Th17 cells and Tregs represent an intriguing issue to be addressed in lung cancer pathogenesis. Tregs play an important role in the preservation of self-tolerance and modulation of overall immune responses against tumor cells. Th17 cells directly or via other proinflammatory cytokines modulate antitumor immune responses. Notably, there is a close relation between Tregs and Th17 cells. However, the possible interaction between these subsets in lung cancer remains to be elucidated. In this setting, targeting Treg/Th17 balance for therapeutic purposes may represent a useful tool for lung cancer treatment in the future. The purpose of this review is to discuss recent findings of the role of these novel populations in lung cancer immunity and to highlight the pleiotropic effects of these subsets on the development and regulation of lung cancer. [ABSTRACT FROM AUTHOR]