3,937 research outputs found

    FMNL1 promotes growth and metastasis of breast cancer by inhibiting BRCA1 via upregulation of HMGA1

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    In the earlier published article, “Herbei Province” included in the affiliation of the second author is incorrect. “Chongqing” is a municipality directly under the Central Government and does not belong to "Hebei Province”. At the request of the author, the correct affiliation is provided above. New citation: Zhang Q, Yang H, Tang C, Wang Q, Ren L, Jia C, et al. FMNL1 promotes growth and metastasis of breast cancer by inhibiting BRCA1 via upregulation of HMGA1. Trop J Pharm Res 2021; 20(8):1559-1564 doi: 10.4314/tjpr.v20i8.2. Erratum: 2022; 21(8): 1807 doi: 10.4314/ tjpr.v 21i8.31 Earlier citation: Zhang Q, Yang H, Tang C, Wang Q, Ren L, Jia C, et al. FMNL1 promotes growth and metastasis of breast cancer by inhibiting BRCA1 via upregulation of HMGA1. Trop J Pharm Res 2021; 20(8):1559-1564 doi: 10.4314/tjpr.v20i8.

    Vehicle Routing Problems with Fuel Consumption and Stochastic Travel Speeds

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    Conventional vehicle routing problems (VRP) always assume that the vehicle travel speed is fixed or time-dependent on arcs. However, due to the uncertainty of weather, traffic conditions, and other random factors, it is not appropriate to set travel speeds to fixed constants in advance. Consequently, we propose a mathematic model for calculating expected fuel consumption and fixed vehicle cost where average speed is assumed to obey normal distribution on each arc which is more realistic than the existing model. For small-scaled problems, we make a linear transformation and solve them by existing solver CPLEX, while, for large-scaled problems, an improved simulated annealing (ISA) algorithm is constructed. Finally, instances from real road networks of England are performed with the ISA algorithm. Computational results show that our ISA algorithm performs well in a reasonable amount of time. We also find that when taking stochastic speeds into consideration, the fuel consumption is always larger than that with fixed speed model

    A wear-resistant metastable CoCrNiCu high-entropy alloy with modulated surface and subsurface structures

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    Sliding friction-induced subsurface structures and severe surface oxidation can be the major causes influencing the wear resistance of ductile metallic materials. Here, we demonstrated the role of subsurface and surface structures in enhancing the wear resistance of an equiatomic metastable CoCrNiCu high-entropy alloy (HEA). The CoCrNiCu HEA is composed of a CoCrNi-rich face-centered cubic (FCC) dendrite phase and a Cu-rich FCC inter-dendrite phase. Copious Cu-rich nano-precipitates are formed and distributed uniformly inside the dendrites after tuning the distribution and composition of the two phases by thermal annealing. Although the formation of nano-precipitates decreases the hardness of the alloy due to the loss of solid solution strengthening, these nano-precipitates can be deformed to form continuous Cu-rich nanolayers during dry sliding, leading to a self-organized nano-laminated microstructure and extensive hardening in the subsurface. In addition, the nano-precipitates can facilitate the formation of continuous and compacted glaze layers on the worn surface, which are also beneficial for the reduction of the wear rate of CoCrNiCu. The current work can be extended to other alloy systems and might provide guidelines for designing and fabricating wear-resistant alloys in general

    A machine learning method for locating subsynchronous oscillation source of VSCs in wind farm induced by open-loop modal resonance based on measurement

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    In recent years, sub-synchronous oscillation incidents have been reported to happen globally, which seriously threatens the safe and stable operation of the power system. It is difficult to locate the oscillation source in practice using the parameterized model of open-loop modal resonance. Therefore, this paper aims at the problem of oscillation instability caused by the interaction between the multiple voltage source converters in the wind farm grid-connected system, proposes a method for locating the oscillation source of a wind farm using measurement data based on the transfer learning algorithm of transfer component analysis. At the same time, in order to solve the problem of the lack of oscillation data and the inability to label in the real system, a simplified simulation system was proposed to generate large batches of labeled training samples. Then, the common features of the samples from simulation system and the real system were learned through the transfer component analysis algorithm. Afterward, a classifier was trained to classify samples with common features. Finally, two grid-connected wind farms with VSC access are used to verify that the proposed method has good locating performance. This has important reference value for the practical application of power grid dispatching and operation using measurement to identify oscillation sources

    Effects of dietary protein on milk yield and colostrum whey protein composition of tibetan sheep in modern intensive-fed pattern

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    Colostrum protein, an essential source of dietary nutrients, could improve new-born animals" immunity, and play a vital role in mammals" early development. In order to explore the milk yield and colostrum whey protein composition of Tibetan sheep, 120 Tibetan sheep were arbitrarily separated into categories, namely treatment groups (A, B, C) and control group (D). Compositional and functional differences in milk yield and colostrum whey protein composition among different dietary proteins were compared using proteomics methods. The results showed that sheep with 14% protein level diet group (group B) had the least bodyweight loss and higher milk yield during lactation compared to the other groups. Fifty differentially expressed proteins (DEPs) were recognized using iTRAQ, these DEPs were analyzed based on cluster, GO, KEGG and PPIs analysis. GO-BP involved were Protein transmembrane transport, Protein regulation metabolic process, Biological regulation, Regulation of biological process, and Response to stimulus. Meantime, DEPs participated in many KEGG pathways, including Fatty acid metabolism, Glycerophospholipid metabolism, Protein digestion and absorption, Ras signaling pathway and Cell adhesion molecules. The treatment groups showed increase in the abundance of regulation metabolic process (especially protein metabolism and fatty acid metabolism), along with decrease in stress reaction process. Lactoferrin, Alpha-S2-casein, Superoxide dismutase [Cu-Zn], Alpha-s1-casein, Alpha globin and Lactoperoxidase appeared in the center of the PPi network intersection. Interestingly, 14% protein group (group B) had exhibited the greatest variability between biological relevance in milk composition and function, these results could increase the understanding of different dietary protein on colostrum whey protein composition of Tibetan sheep, which could provide important information and potential directions for the infant milk powder and functional food industries

    Dopamine receptor activation modulates GABA neuron migration from the basal forebrain to the cerebral cortex

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    GABA neurons of the cerebral cortex and other telencephalic structures are produced in the basal forebrain and migrate to their final destinations during the embryonic period. The embryonic basal forebrain is enriched in dopamine and its receptors, creating a favorable environment for dopamine to influence GABA neuron migration. However, whether dopamine receptor activation can influence GABA neuron migration is not known. We show that dopamine D1 receptor activation promotes and D2 receptor activation decreases GABA neuron migration from the medial and caudal ganglionic eminences to the cerebral cortex in slice preparations of embryonic mouse forebrain. Slice preparations from D1 or D2 receptor knock-out mouse embryos confirm the findings. In addition, D1 receptor electroporation into cells of the basal forebrain and pharmacological activation of the receptor promote migration of the electroporated cells to the cerebral cortex. Analysis of GABA neuron numbers in the cerebral wall of the dopamine receptor knock-out mouse embryos further confirmed the effects of dopamine receptor activation on GABA neuron migration. Finally, dopamine receptor activation mobilizes striatal neuronal cytoskeleton in a manner consistent with the effects on neuronal migration. These data show that impairing the physiological balance between D1 and D2 receptors can alter GABA neuron migration from the basal forebrain to the cerebral cortex. The intimate relationship between dopamine and GABA neuron development revealed here may offer novel insights into developmental disorders such as schizophrenia, attention deficit or autism, and fetal cocaine exposure, all of which are associated with dopamine and GABA imbalance

    Feeding a low-protein maternal diet affects qinghai bamei piglet jejunal structure and microbial function response

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    This experiment investigated the impacts of feeding a maternal low-CP concentration diet having iso-essential amino acids on newborn suckling piglet"s intestinal microbial composition and function. Forty randomly selected purebred Bamei sows were divided into two groups and fed a low dietary CP (12%, LP) or a normal CP (14%, CON) diet, respectively, but formulated to contain similar (iso-) essential amino acid concentrations per current recommendations. At 21 days, 12 piglets were randomly selected from each treatment and euthanized with jejunum content samples collected. The 16S rRNA gene sequencing was combined as an integrated approach for evaluating the functional impact of maternal CP concentrations on piglet intestinal microbiome. Even though piglets demonstrated similar 0 to 21 d ADG among treatments, the jejunum relative weight, villus width, crypt depth and muscular thickness were increased (P<0.05), while villus height, and villus height/crypt depth were reduced (P<0.05) for the material LP compared to the maternal fed CON diet. Maternal CP concentrations can modify the intestinal microbial composition of Bamei suckling piglets. The relative abundances of the bacterial species Escherichia-Shigella, Actinobacillus, Clostridium_sensu_stricto_1, Veillonella, and Turicibacter were increased (P<0.05) in the maternal LP fed diet compared with the maternal fed CON diet microbiota metabolites. Overall, LP diet contributed to improve piglet intestinal histomorphology, microbial composition and function

    Bioluminescence Imaging of Heme Oxygenase-1 Upregulation in the Gua Sha Procedure

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    Gua Sha is a traditional Chinese folk therapy that employs skin scraping to cause subcutaneous microvascular blood extravasation and bruises. The protocol for bioluminescent optical imaging of HO-1-luciferase transgenic mice reported in this manuscript provides a rapid in vivo assay of the upregulation of the heme oxygenase-1 (HO-1) gene expression in response to the Gua Sha procedure. HO-1 has long been known to provide cytoprotection against oxidative stress. The upregulation of HO-1, assessed by the bioluminescence output, is thought to represent an antioxidative response to circulating hemoglobin products released by Gua Sha. Gua Sha was administered by repeated strokes of a smooth spoon edge over lubricated skin on the back or other targeted body part of the transgenic mouse until petechiae (splinter hemorrhages) or ecchymosis (bruises) indicative of extravasation of blood from subcutaneous capillaries was observed. After Gua Sha, bioluminescence imaging sessions were carried out daily for several days to follow the dynamics of HO-1 expression in multiple internal organs

    Prevalence and clinical characteristics of lower limb atherosclerotic lesions in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study

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    BACKGROUND: The clinical features of atherosclerotic lesions in ketosis-onset diabetes are largely absent. We aimed to compare the characteristics of lower limb atherosclerotic lesions among type 1, ketosis-onset and non-ketotic type 2 diabetes. METHODS: A cross-sectional study was performed in newly diagnosed Chinese patients with diabetes, including 53 type 1 diabetics with positive islet-associated autoantibodies, 208 ketosis-onset diabetics without islet-associated autoantibodies, and 215 non-ketotic type 2 diabetics. Sixty-two subjects without diabetes were used as control. Femoral intima-media thickness (FIMT), lower limb atherosclerotic plaque and stenosis were evaluated and compared among the four groups based on ultrasonography. The risk factors associated with lower limb atherosclerotic plaque were evaluated via binary logistic regression in patients with diabetes. RESULTS: After adjusting for age and sex, the prevalence of lower limb plaque in the patients with ketosis-onset diabetes (47.6%) was significantly higher than in the control subjects (25.8%, p = 0.013), and showed a higher trend compared with the patients with type 1 diabetes (39.6%, p = 0.072), but no difference was observed in comparison to the patients with non-ketotic type 2 diabetes (62.3%, p = 0.859). The mean FIMT in the ketosis-onset diabetics (0.73 ± 0.17 mm) was markedly greater than that in the control subjects (0.69 ± 0.13 mm, p = 0.045) after controlling for age and sex, but no significant differences were found between the ketosis-onset diabetics and the type 1 diabetics (0.71 ± 0.16 mm, p = 0.373), and the non-ketotic type 2 diabetics (0.80 ± 0.22 mm, p = 0.280), respectively. Age and FIMT were independent risk factors for the presence of lower limb plaque in both the ketosis-onset and non-ketotic type 2 diabetic patients, while sex and age in the type 1 diabetic patients. CONCLUSIONS: The prevalence and risk of lower limb atherosclerotic plaque in the ketosis-onset diabetes were remarkably higher than in the control subjects without diabetes. The features and risk factors of lower limb atherosclerotic lesions in the ketosis-onset diabetes resembled those in the non-ketotic type 2 diabetes, but different from those in the type 1 diabetes. Our findings provide further evidences to support the classification of ketosis-onset diabetes as a subtype of type 2 diabetes rather than idiopathic type 1 diabetes

    Identification of <em>CHIP</em> as a novel causative gene for autosomal recessive cerebellar ataxia

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    Autosomal recessive cerebellar ataxias are a group of neurodegenerative disorders that are characterized by complex clinical and genetic heterogeneity. Although more than 20 disease-causing genes have been identified, many patients are still currently without a molecular diagnosis. In a two-generation autosomal recessive cerebellar ataxia family, we mapped a linkage to a minimal candidate region on chromosome 16p13.3 flanked by single-nucleotide polymorphism markers rs11248850 and rs1218762. By combining the defined linkage region with the whole-exome sequencing results, we identified a homozygous mutation (c.493CT) in CHIP (NM_005861) in this family. Using Sanger sequencing, we also identified two compound heterozygous mutations (c.389AT/c.441GT; c.621C>G/c.707GC) in CHIP gene in two additional kindreds. These mutations co-segregated exactly with the disease in these families and were not observed in 500 control subjects with matched ancestry. CHIP colocalized with NR2A, a subunit of the N-methyl-D-aspartate receptor, in the cerebellum, pons, medulla oblongata, hippocampus and cerebral cortex. Wild-type, but not disease-associated mutant CHIPs promoted the degradation of NR2A, which may underlie the pathogenesis of ataxia. In conclusion, using a combination of whole-exome sequencing and linkage analysis, we identified CHIP, encoding a U-box containing ubiquitin E3 ligase, as a novel causative gene for autosomal recessive cerebellar ataxia
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