Developmental stage related patterns of codon usage and genomic GC content: searching for evolutionary fingerprints with models of stem cell differentiation

Developmental-stage-related patterns of gene expression correlate with codon usage and genomic GC content in stem cell hierarchies

Ethnopharmacokinetic- and Activity-Guided Isolation of a New Antidepressive Compound from Fructus Aurantii Found in the Traditional Chinese Medicine Chaihu-Shugan-San: A New Approach and Its Application

Aims. We aimed to identify an antidepressive compound found in traditional Chinese medicine (TCM) by a new approach called ethnopharmacokinetic- and activity-guided isolation (EAGI). Methods. The new approach targets an unknown chromatographic peak produced by an absorbed compound found in oral Chaihu-Shugan-San (CSS) taken by patients with depression. Once the compound was isolated from Fructus Aurantii (FA), spectral data was employed to identify the compound. The effects of this compound, FA, and CSS on depressive behaviors were investigated. Results. The identified compound was merazin hydrate (MH) according to the new approach. MH, FA, and CSS significantly reduced immobility time and increased locomotor activity. The effects of MH, FA and CSS were similar to Fluoxetine at high doses. Conclusion. MH, a compound whose antidepressive effect is similar to FA and CSS, was isolated for the first time from FA via targeting its corresponding unknown chromatographic peak, and its antidepressive effect was compared with FA or CSS. These findings highlight the potential for drug R&D and pharmacological research of ∼100,000 TCMs

Reduced Energy Metabolism Impairs T Cell-Dependent B Cell Responses in Patients With Advanced HBV-Related Cirrhosis

Background and AimsPatients with decompensated HBV-related liver cirrhosis (HBV D-LC) showed compromised immune responses, which manifested as a proneness to develop infections and hyporesponsiveness to vaccines, resulting in accelerated disease progression. The alterations in T cell-dependent B cell responses in this pathophysiological process were not well understood. This study aimed to investigate T cell-dependent B cell responses in this process and discuss the mechanism from the perspective of metabolism.MethodsChanges in phenotypes and subsets of peripheral B cells between HBV D-LC patients and healthy controls (HCs) were compared by flow cytometry. Isolated B cells were activated by coculture with circulating T follicular (cTfh) cells. After coculture, the frequencies of plasmablasts and plasma cells and immunoglobin levels were analyzed. Oxidative phosphorylation (OXPHOS) and glycolysis were analyzed by a Seahorse analyzer. Mitochondrial function and the AKT/mTOR pathway were analyzed by flow cytometry.ResultsThe proliferation and differentiation capacities of B cells after T cell stimulation were impaired in D-LC. Furthermore, we found that B cells from D-LC patients showed reductions in OXPHOS and glycolysis after activation, which may result from reduced glucose uptake, mitochondrial dysfunction and attenuated activation of the AKT/mTOR pathway.ConclusionsB cells from HBV D-LC patients showed dysfunctional energy metabolism after T cell-dependent activation. Understanding the regulations of B cell metabolic pathway and their changes may provide a new direction to rescue B cell hyporesponsiveness in patients with HBV D-LC, preventing these patients be infected and improving sensitivity to vaccines

Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate

This study investigated the effects of pregnane X receptor (PXR/NR1I2) and CYP2B6 genetic variants on sodium ferulate (SF)-mediated induction of bupropion hydroxylation. The pharmacokinetics of bupropion and hydroxybupropion were evaluated after an oral dose of bupropion (150 mg) administered with and without SF pretreatment for 14 days in 33 healthy subjects. The area under the time-concentration curve (AUC) ratio of AUC_hyd (AUC(0-∞) of hydroxybupropion)/AUC_bup (AUC(0-∞) of bupropion) represents the CYP2B6 hydroxylation activity, which was significantly lower in CYP2B6*6 carriers (NR1I2 TGT noncarriers or carriers) than in noncarriers in both the basal and SF-induced states (p-value<0.05). AUC ratio and AUC_hyd of NR1I2 -24113AA variant were markedly lower than GA and GG genotypes (7.5±2.1 versus 14.5±3.3 and 20.6±1.1, and 8873±1431 versus 14,504±2218 and 17,586±1046) in the induced states. However, -24020(-)/(-) variant didn't show significant difference in the induction of CYP2B6 hydroxylation activity by SF compared with other -24020[GAGAAG]/(-) genotypes. NR1I2 TGT haplotype (-25385T+g.7635G+g.8055T) carriers exhibited a significantly decreased AUC ratio, compared with TGT noncarriers, in the basal states (7.6±1.0 versus 9.7±1.0), while this result wasn't observed in CYP2B6*6 noncarriers. Moreover, individuals with complete mutation-type [CYP2B6*6/*6+NR1I2 TGT+ -24113AA+ -24020 (-)/(-)] showed even lower percent difference of AUC ratio (8.7±1.2 versus 39.5±8.2) than those with complete wild-type. In conclusion, it is suggested that NR1I2 variants decrease the bupropion hydroxylation induced by SF treatment, particularly in CYP2B6*6 carriers

MASALAH-MASALAH PEMBELAJARAN YANG DIHADAPI WIDYAISWARA : Studi Kasus Pada Lembaga Diktat Pemda Tk.I Propinsi Bengkulu

<div><p>Rat strains differ dramatically in their susceptibility to mammary carcinogenesis. On the assumption that susceptibility genes are conserved across mammalian species and hence inform human carcinogenesis, numerous investigators have used genetic linkage studies in rats to identify genes responsible for differential susceptibility to carcinogenesis. Using a genetic backcross between the resistant Copenhagen (Cop) and susceptible Fischer 344 (F344) strains, we mapped a novel mammary carcinoma susceptibility (<i>Mcs30</i>) locus to the centromeric region on chromosome 12 (LOD score of ∼8.6 at the D12Rat59 marker). The <i>Mcs30</i> locus comprises approximately 12 Mbp on the long arm of rat RNO12 whose synteny is conserved on human chromosome 13q12 to 13q13. After analyzing numerous genes comprising this locus, we identified <i>Fry</i>, the rat ortholog of the furry gene of <i>Drosophila melanogaster,</i> as a candidate <i>Mcs</i> gene. We cloned and determined the complete nucleotide sequence of the 13 kbp <i>Fry</i> mRNA. Sequence analysis indicated that the <i>Fry</i> gene was highly conserved across evolution, with 90% similarity of the predicted amino acid sequence among eutherian mammals. Comparison of the <i>Fry</i> sequence in the Cop and F344 strains identified two non-synonymous single nucleotide polymorphisms (SNPs), one of which creates a putative, de novo phosphorylation site. Further analysis showed that the expression of the <i>Fry</i> gene is reduced in a majority of rat mammary tumors. Our results also suggested that FRY activity was reduced in human breast carcinoma cell lines as a result of reduced levels or mutation. This study is the first to identify the <i>Fry</i> gene as a candidate <i>Mcs</i> gene. Our data suggest that the SNPs within the <i>Fry</i> gene contribute to the genetic susceptibility of the F344 rat strain to mammary carcinogenesis. These results provide the foundation for analyzing the role of the human <i>FRY</i> gene in cancer susceptibility and progression.</p></div

A new strategy to transform mono and bimetallic non-noble metal nanoparticles into highly active and chemoselective hydrogenation catalysts

A new strategy to transform non-noble metal oxide nanoparticles (NPs) into highly active and selective metallic NPs as hydrogenation catalysts by a simple carbon coating process based on hydrothermal treatment with glucose is presented. During the carbon coating process, metal oxide NPs will be reduced to metallic NPs and covered by thin carbon layers, resulting in formation of Metal@C NPs. Through this method, monometallic Co@C has been prepared, which shows excellent activity and selectivity for chemoselectivity hydrogenation of substituted nitroarenes to corresponding anilines under mild conditions. Kinetic, isotopic and spectroscopic studies indicate that hydrogen dissociation-addition is the controlling step in chemoselective hydrogenation reaction with Co@C NPs. Stabilization and the reaction rate of metallic Co are improved by preparing bimetallic CoNi@C catalyst, leading to almost fivefold improved activity. Our preparation method enables to synthesize non-noble bimetallic CoNi@C nanoparticles with nearly one-order magnitude higher activity than any Co-based non-noble metal catalysts prepared by other methods, without necessity to involve the promoting role of metal-N interactions. At last, we also show the application of Co@C NPs for hydrogenation of levulinic acid to γ-valerolactone.L.L. thanks ITQ for providing a contract. F.G. thanks the financial support from Jiangsu Key Laboratory of Vehicle Emissions Control. The authors also thank Microscopy Service of UPV for kind help on TEM and STEM measurements. Financial supports by the “Severo Ochoa” and ERC-AdG-2014-671093—SynCatMatch program are also gratefully acknowledged.Peer Reviewe

The important role of miR-1-3p in cancers

Abstract Cancer is a malignant tumor that seriously threatens human life and health. At present, the main treatment methods include surgical resection, chemotherapy, radiotherapy, and immunotherapy. However, the mechanism of tumor occurrence and development is complex, and it produces resistance to some traditional treatment methods, leading to treatment failure and a high mortality rate for patients. Therefore, exploring the molecular mechanisms of tumor occurrence, development, and drug resistance is a very important task. MiRNAs are a type of non-coding small RNA that regulate a series of biological effects by binding to the 3′-UTR of the target mRNA, degrading the mRNA, or inhibiting its translation. MiR-1-3p is an important member of them, which is abnormally expressed in various tumors and closely related to the occurrence and development of tumors. This article introduces miR-1-3p from multiple aspects, including its production and regulation, role in tumor occurrence and development, clinical significance, role in drug resistance, and approaches for targeting miR-1-3p. Intended to provide readers with a comprehensive understanding of the important role of miR-1-3p in tumors. Graphical Abstrac

Vibration wave downhole communication technique

To overcome the disadvantages of traditional downhole communication methods, a vibration wave downhole communication technique is proposed, and a vibration wave downhole communication system is developed. This technique has been verified by field test and is applied to separated layer water injection. It is shown by theoretical and test research that transmission of the vibration wave through tubing and casing appears as the alternate distribution of pass-band and stop-band. According to that, a multi-baseband transmission strategy is formulated. The on-off keying modulation and Manchester encoding scheme are used to load the control information into the vibration wave. A generation system of vibration signals is developed to realize the controllable conversion from electric energy into vibration wave energy. A receiving and decoding system of vibration waves, which uses a micro-vibration acceleration sensor as the signal pickup element, is developed too. A test system for vibration wave downhole remote transmission is designed and applied to field test. The feasibility of the technique and the accuracy and reliability of communication system are verified and the attenuation characteristics of casing vibration wave signals are obtained. This technique has been applied to separated layer water injection successfully with wide application prospect in wellbore control field. Key words: vibration wave, downhole communication, on-off-keying modulation, Manchester encoding, magne-tostrictive material, micro-vibration acceleration senso

Machine Learning-Based Optimization of Synchronous Rectification Low-Inductance Current Secondary Boost Converter (SLIC-QBC)

For recycling waste batteries, high-gain DC-DC provides a great solution. In this article, the design and optimization of a high-gain converter–synchronous rectification low-inductance current secondary boost converter (SLIC-QBC) is studied. The optimization objective of this article is to propose an automatic design method for passive components and the switching frequency of the converter to improve efficiency and power density. A machine learning-integrated optimization method is proposed to minimize the converter mass and power loss of the converter. In this method, first, a component-based automatic design model is built with embedded SLIC-QBC simulation. Then, a series of design schemes is generated within a large parameter range, and training data for machine learning are collected. Support vector machine (SVM) and artificial neural network (ANN) are used to validate the converter design scheme, where ANN establishes the mapping relationship from design parameters to optimization objectives. After the optimization, an experimental prototype is built for experimental verification. The simulation and experimental results verify the practicability of the proposed method