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Perfluorooctane sulfonate (PFOS) is a global environmental contaminant known to cause neurotoxicity. However, the specific targets of its neurotoxic effects remain poorly understood. In this study, we aimed to investigate the differential protein expression associated with brain tissue toxicity induced by potassium perfluorooctane sulfonate (PFOS-K) and predict its potential biological functions. Rattus norvegicus were treated with 10 mg/kg PFOS-K for 30 days to establish a toxicity model, and brain tissue morphology was examined using HE and nissl staining. Protein expression profiles were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Bioinformatics tools were used to analyze protein functions, and immunofluorescence was employed to detect the expression of the ENO2 gene in whole brain tissue.PFOS exposure resulted in changes in neuronal cell morphology in different regions of the rat hippocampus, including cell vacuolation, reduced neuronal axon length and density, and decreased nisomes in the DG region. PFOS-K exposure led to changes in protein expression profiles in brain tissue, with 53 differentially expressed proteins identified. Gene ontology (GO) and pathway analysis revealed that the main function of these proteins is to participate in the mitochondrial oxidative respiratory electron transport chain. The main signaling pathways involved include glycolysis, glutamine conversion, Wnt signaling pathway, energy metabolism, oxidative stress, and inflammatory-mediated cytokine signaling. PFOS-K exposure may primarily promote mitochondrial oxidative respiratory electron transport chain, elevate cytoplasmic Glu levels, and disrupt Ga2+ homeostasis. It induces mitochondrial pathway-dependent apoptosis, while also significantly down-regulating the expression of the neurotrophic and protective factor ENO2 in the pyramidal layer of the hippocampus, which may ultimately result in neuronal pathological damage and brain tissue toxicity through energy metabolism.

Treatment of human estrogen receptor (ER)-positive breast cancer (ER+ BC) using conventional chemotherapy remains a challenge and is often ineffective as a result of tumor metastasis. The present study aimed to investigate the ability of narasin, an ionophore antibiotic, to potentially inhibit tumor metastasis and growth in human ER+ BC. Narasin was found to have significant inhibitory abilities on cell proliferation, migration and invasion in ER+ BC cell lines MCF-7 and T47D compared with the triple-negative BC cell MDA-MB-231. For the in vivo studies, narasin effectively decreased the number of tumor metastasis nodules, tumor volume and weight without apparent toxicity in human MCF-7 nude mouse left ventricle injection tumor metastasis and xenograft models. Mechanistically, it demonstrated that exposure to TGF-β or IL-6 induced the expression of epithelial-mesenchymal transition (EMT) markers in ER+ BC cell lines. On the contrary, narasin dose-dependently reversed EMT by increasing the expression of E-cadherin and decreasing the expression of N-cadherin, vimentin, β-catenin and zinc finger E-box-binding homeobox 1 at the protein and gene expression levels. Gene microarray, molecular docking and western blotting were performed to demonstrate that those protein and gene expression levels are regulated by the inactivation of the TGF-β/phosphorylated (p)-SMAD3 and IL-6/p-STAT3 signaling pathways. Taken together, these findings indicated that narasin may be a promising candidate that can be further optimized for the treatment of human ER+ BC.

Background: The role of T cell Ig and ITIM domain (TIGIT) and programmed cell death-1 (PD-1) in colorectal cancer (CRC) with mismatch repair deficiency is unknown.Methods: This was a study of 60 CR...

BACKGROUND Cytochrome P450 (CYP) genes are necessary for the production or metabolism of fetal sex hormones during pregnancy. The second-to-fourth digit ratio (2D: 4D) is formed in the early stage of human fetal development and considered an indicator reflecting prenatal sex steroids levels. We explored the association between 2D: 4D and single-nucleotide polymorphisms (SNPs) of CYP. MATERIAL AND METHODS Correlation analysis between 2D: 4D and 8 SNPs, rs2687133 (CPY3A7), rs7173655 (CYP11A1), rs1004467, rs17115149, and rs2486758 (CYP17A1), and rs4646, rs2255192, rs4275794 (CYP19A1), was performed using data from 426 female and 412 male Chinese university students. SNP genotyping was conducted using PCR. Digit lengths were photographed and measured by image processing software. RESULTS rs2486758 (CYP17A1) correlated with left hand 2D: 4D in men (P=0.026), and rs1004467 (CYP17A1) correlated with right hand 2D: 4D in men (P=0.008) and the whole population (P=0.032). In men, allele G rs1004467 decreased right hand 2D: 4D, while allele C of rs2486758 increased left hand 2D: 4D. In women, left hand 2D: 4D was higher in genotypes with allele A of SNP rs4646 (CYP19A1) under the dominant genetic model; female DR-L was higher in genotypes with allele T of rs17115149 (CYP11A1). SNPs rs2687133 (CYP3A7) and rs1004467 (CYP17A1) were significantly correlated with right hand 2D: 4D (P=0.0107). CONCLUSIONS SNPs rs1004467 and rs2486758 of CYP17A1 are significant in the relationship between 2D: 4D and CYP gene polymorphisms under different conditions. SNP interactions between CYP genes probably impact 2D: 4D. The correlation between 2D: 4D and some sex hormone-related diseases may be due to the effect of CYP variants on the 2 phenotypes.

Autophagy plays an important role in the fight against Mycobacterium tuberculosis infection. Massive researches proved that miRNAs could be the regulators of autophagy, which implied miRNAs could favor MTB invasion or latent infection. In our study, multiple bioinformatics databases and software were used to seek and lock the miRNAs associating with regulation of autophagy. Notably, a novel miR-129-3p was found and its target gene Atg4b showed grand potential in mediation of autophagy. Moreover, BCG infection triggered miR-129-3p overexpression in RAW264.7 cells. Up-regulation of miR-129-3p decreased mRNA or protein level of Atg4b and resulted in the inhibition of autophagy. The antagomir of miR-129-3p had the opposite impact. The LC3 puncta formation in RAW264.7 cells were also affected after transfection of miR-129-3p mimic or antagomir. The mRFP-GFP-LC3 analysis indicated that mimic of miR-129-3p impaired autophagic flux while antagomir improved autophagy. The CFU assay results showed that miR-129-3p promoted the intracellular survival of BCG in macrophages. Consequently, these data suggested that miR-129-3p could favor MTB survival by inhibiting autophagy via Atg4b.

Yanan Zhang,1 Jie Qiu,1 Peng Zhang,1 Jin Zhang,1 Min Jiang,2 Zhanbing Ma3 1Department of Respiratory and Critical Care Medicine, General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan, People’s Republic of China; 2National Engineering Research Center for Beijing Biochip Technology, Sub-center in Ningxia, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 3Department of Medical Genetic and Cell Biology, Ningxia Medical University, Yinchuan, People’s Republic of China Background: Genome-wide association studies identified several genomic regions associated with the risk of chronic obstructive pulmonary disease (COPD), including the 4q22 and 15q25 regions. These regions contain the FAM13A and IREB2 genes, which have been associated with COPD but data are lacking for Chinese patients. The objective of the study was to identify new genetic variants in the FAM13A and IREB2 associated with COPD in Northwestern China.Methods: This was a case-control study performed in the Ningxia Hui Autonomous Region between January 2014 and December 2016. Patients were grouped as COPD and controls based on FEV1/FVC

Heroin abuse is linked to a deleterious effect on cognitive functioning in the individual. Recent evidences suggest that the serotonin7 receptor (5-HT7R) is engaged in the regulation of cognitive control and the drug use-associated behaviors. However, the role of 5-HT7R in the cognitive control after acute heroin administration has not been studied. The present study aims to investigate whether the knockdown of the 5-HT7R by virus-mediated gene silencing in the medial prefrontal cortex (mPFC) could ameliorate the acute heroin-induced cognitive impairments. The attentional function, impulsivity and compulsivity were assessed by the 5-choice serial reaction time task (5-CSRTT) in mice. The memory ability and locomotor activity were examined by the novel objects recognition (NOR), Y-maze and open-field test (OFT). Acute heroin administration at 5 mg/kg produced robust disruptions in attention, impulsivity and motivation in mice. 5-HT7R knockdown in the mPFC did not affect the 5-CSRTT baseline performance, spatial working memory, visual episodic memory and locomotion. However, mPFC 5-HT7R knockdown selectively ameliorated acute heroin-induced increase in omissions and premature responses under conditions of increased perceptual load. In addition, mPFC 5-HT7R knockdown induced increases in perseverative responding observed across both saline and heroin-treated animals. Moreover, 5-HT7R knockdown prevented the heroin-induced decrease in NR1/CaMKII phosphorylation in mPFC, thus suggesting that 5-HT7R and N-methyl- d -aspartic acid (NMDA) receptor signaling may be involved in the cognitive outcomes of acute heroin administration. Altogether, these observations suggest modest and restricted effects of mPFC 5-HT7R knockdown on cognitive behaviors, both in the presence or absence of acute heroin treatment.

Long noncoding RNAs (lncRNAs) are a class of functional non-coding transcripts that are longer than 200 nt and regulate gene expression via diverse mechanisms in eukaryotes. In fact, they have emerged as critical epigenetic and transcriptional regulators of autophagy in mammals in response to various stressors. Autophagy not only plays a crucial role in maintaining cellular homeostasis, but it is also essential to immunity, targets intracellular pathogens for degradation, modulates inflammation, and participates in adaptive immune responses. However, the expression profile of lncRNA and its role in regulating autophagy in macrophages have been poorly defined. Here, we used transcriptomic and bioinformatics to analysis LncRNA expression profile during autophagy and functional studies to evaluate the function of the metastasis-associated lung adenocarcinoma transcript-1 (Malat1) lncRNA in macrophages. A total of 1112 putative lncRNAs (240 novel lncRNAs) were identified, including 831 large intergenic, 129 intronic, and 152 anti-sense lncRNA, of which 59 differentially expressed transcripts exhibited a greater than 1.5-fold change under different conditions. The interaction of Malat1 lncRNA with microRNA (mir)-23-3p and lysosomal-associated membrane protein 1 (Lamp1) was found, Malat1 releases inhibition of Lamp1 expression in macrophages through competitive adsorption of mir-23-3p. The results of this study provide a better understanding of lncRNA function in macrophages and a basis for further investigation into the roles and mechanisms of ncRNA in immunology, particularly the functions of Malat1 and mir-23-3p in the pathogenesis of macrophages.

OBJECTIVES Digit ratio, especially the second-to-fourth digit ratio (2D:4D), is a proxy indicator for prenatal exposure and sensitivity to sexual hormones which may influence the susceptibility to certain cancers. The aim of the present study was to investigate whether there is a possible association between 2D:4D and gastric cancer (GCA) in north Chinese women. METHODS Photographs of the left and right hands of 167 women (controls: 113; patients: 54) were collected. Left hand, right hand, and right minus left hand (Dr-l) 2D:4D were analyzed and compared. RESULTS The GCA group presented significantly lower 2D:4D than controls (left: P

Sex steroid exposure during human development may influence disease susceptibility. Second to fourth digit ratio (2D:4D) is thought to be a putative biomarker for prenatal hormone level during foetal life. Recently there has been a great deal of interest in 2D:4D and risk of disease in adulthood.We explored the relationship between 2D:4D ratio and coronary heart disease. Photocopies of the two hands of 310 males (controls: 155; patients: 155) were collected at Yin chuan city, in the Ningxia province of China. Left hand, right hand, mean hand and right minus left 2D:4D (Dr-l) were analysed.The mean values of 2D:4D ratio in patients were higher than those of CSIN controls. The patients showed significantly higher 2D:4D (left hand: P0.01; right hand, mean hand: P0.05) than controls. In patients, 2D:4D (especially left hand 2D:4D) were inversely associated with age at diagnosis (left hand: P0.001; right hand, mean hand: P0.05). No association between Dr-l and age or age at presentation of disease was observed in the groups.2D:4D may correlate particularly with risk of coronary heart disease in Chinese men.

Digit ratio, especially second-to-fourth digit ratio (2D:4D) is used as a biomarker of prenatal testosterone exposure and was found associated with physical ability, such as handgrip strength (HGS). Recently, this association has been discussed in several ethnic groups.To investigate correlations between 2D:4D and HGS in Chinese population of Ningxia Hui ethnicity.Here we firstly present the evidence on digit ratio and HGS of 346 college students (119 males and 227 females) by collecting photographs and HGS of both hands at Yinchuan city, in the Ningxia province of China.Females have higher mean values of digit ratio than males; significant variances of 3D:5D (left and right: P0.05), 2D:3D, 3D:4D (left and right: P0.01) and 2D:4D, 2D:5D (left and right: P0.001) were found between different sex. Males showed significantly greater HGS than females on both hands. 2D:4D of both hands were significantly negative correlated with HGS in females (but not in males).2D:4D ratio is negatively correlated with HGS in a Chinese population (especially in females) of Ningxia Hui ethnicity.

Abscisic acid (ABA)-, stress-, and ripening-induced (ASR) proteins are reported to be involved in abiotic stresses. However, it is not known whether ASR genes confer drought stress tolerance by utilizing the antioxidant system. In this study, a wheat ASR gene, TaASR1, was cloned and characterized. TaASR1 transcripts increased after treatments with PEG6000, ABA and H(2)O(2). Overexpression of TaASR1 in tobacco resulted in increased drought/osmotic tolerance, which was demonstrated that transgenic lines had lesser malondialdehyde (MDA), ion leakage (IL) and reactive oxygen species (ROS), but higher relative water content (RWC) and superoxide dismutase (SOD) and catalase (CAT) activities than wild type (WT) under drought stress. Overexpression of TaASR1 in tobacco also enhanced the expression of ROS-related and stress-responsive genes under osmotic stress. In addition, transgenic lines exhibited improved tolerance to oxidative stress by retaining more effective antioxidant system. Finally, TaASR1 was localized in the cell nucleus and functioned as a transcriptional activator. Taken together, our results showed that TaASR1 functions as a positive factor under drought/osmotic stress, involved in the regulation of ROS homeostasis by activating antioxidant system and transcription of stress-associated genes.

Aquaporin (AQP) proteins have been shown to transport water and other small molecules through biological membranes, which is crucial for plants to combat salt stress. However, the precise role of AQP genes in salt stress response is not completely understood in plants. In this study, a PIP1 subgroup AQP gene, designated TaAQP8, was cloned and characterized from wheat. Transient expression of TaAQP8-green fluorescent protein (GFP) fusion protein revealed its localization in the plasma membrane. TaAQP8 exhibited water channel activity in Xenopus laevis oocytes. TaAQP8 transcript was induced by NaCl, ethylene and H(2)O(2). Further investigation showed that up-regulation of TaAQP8 under salt stress involves ethylene and H(2)O(2) signaling, with ethylene causing a positive effect and H(2)O(2) acting as a negative factor. Overexpression of TaAQP8 in tobacco increased root elongation compared with controls under salt stress. The roots of transgenic plants also retained a high K(+)/Na(+) ratio and Ca(2+) content, but reduced H(2)O(2) accumulation by an enhancement of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) activities under salt stress. Further investigation showed that whole seedlings from transgenic lines displayed higher SOD, CAT and POD activities, increased NtSOD and NtCAT transcript levels, and decreased H(2)O(2) accumulation and membrane injury under salt stress. Taken together, our results demonstrate that TaAQP8 confers salt stress tolerance not only by retaining high a K(+)/Na(+) ratio and Ca(2+) content, but also by reducing H(2)O(2) accumulation and membrane damage by enhancing the antioxidant system.

Background In humans, the relative lengths of the index finger to the ring finger (2D:4D) is a sexually dimorphic trait which correlated with prenatal sex steroids and has been increasingly used as a promising tool to evaluate the impact of prenatal hormone exposure in some traits, such as physical performance. Handgrip strength (HGS) is one potent index of physical ability and its relationship with 2D:4D ratio has been discussed in several ethnic groups. Aims To investigate whether there is a correlation between 2D:4D ratio and HGS in Chinese college students of Ningxia Han ethnicity. Methods 608 students (211 males and 397 females) of Han ethnicity were recruited from Ningxia medical university. Photocopies and HGS of both hands were collected at Yinchuan city, in the Ningxia province of China. Results Sexual dimorphism of 2D:4D and HGS were found, males had significantly lower 2D:4D and greater HGS than females. 2D:4D in both hands were significantly negative correlated with HGS in females and not in males. Conclusions 2D:4D ratio is negative correlated with HGS in a Chinese population of Ningxia Han ethnicity and this association should be considered on the anthropological research within an evolutionary concept in the future.

Background Prenatal gonadal hormones may play a major role in pathogenesis of schizophrenia. It has been reported that second to fourth digit ratio (2D:4D) was influenced by the levels of exposure to prenatal testosterone and estrogen. So, 2D:4D may help to predict the disease susceptibility to schizophrenia. Aims The aim of this study was to investigate the relationship between the digit ratio (2D:4D) and schizophrenia in Chinese population. Methods We recruited 178 schizophrenics (males: 76; females: 102) and 365 controls (males: 218; females: 147) in this study. Photocopies of both hands were collected and left hand, right hand, mean hand and left minus right hand (DL-R) 2D:4D were analyzed. Results The right and mean hand 2D:4D ratios were significantly higher in schizophrenics compared to that of controls in both males and females. The left hand 2D:4D ratio in female schizophrenics was also significantly higher than in controls. Compared to controls, the DL-R 2D:4D in male schizophrenics was obviously higher. There was a weakly (but not significantly) negative correlation between the mean hand 2D:4D ratio and the age of onset. Conclusions The 2D:4D ratio may correlate with the schizophrenia in Chinese population, and it may be an indicator of schizophrenia.

Background: Coronary artery disease (CAD) is an enormous health problem in the world. Dermatoglyphs are cutaneous ridges on the fingers, palms, and soles, formed by genetic regulation and control during early intrauterine life. The Dermatoglyphic traits do not change significantly as the growth of the age. They may be the phenotypic characters of individual genes and represent the predisposition to certain diseases. Aims and Objectives: The study was carried out to document characteristic dermatoglyphic patterns in coronary artery disease which could be useful in early diagnosis of the disease. Materials and Methods: Dermatoglyphic study of 258 male (129 coronary artery disease cases and 129 normal subjects) of Ningxia China were studied in the present cross-sectional study. It involved the digital patterns, ATD angles, A-B ridge counts on the hands. Chi-square test, t-test were used for the statistical analysis in this study. Results: The overall frequency of whorls was higher followed by loop and arch in both two groups. It was observed that there was significant difference of digital frequency of whorls and ulnar loops in patients in both hands as compared to controls (p≤0.01). The mean value of finger ridge counts, total ridge counts were similar between two groups. The A-B ridge counts were significantly higher in coronary artery disease compared with controls on the right palm (p≤0.01). However, the mean ATD angle values were significantly higher in cases than those of in normal on both hands (p

Abscisic acid (ABA)-, stress-, and ripening-induced (ASR) proteins are reported to be involved in abiotic stresses. However, it is not known whether ASR genes confer drought stress tolerance by utilizing the antioxidant system. In this study, a wheat ASR gene, TaASR1, was cloned and characterized. TaASR1 transcripts increased after treatments with PEG6000, ABA and H(2)O(2). Overexpression of TaASR1 in tobacco resulted in increased drought/osmotic tolerance, which was demonstrated that transgenic lines had lesser malondialdehyde (MDA), ion leakage (IL) and reactive oxygen species (ROS), but higher relative water content (RWC) and superoxide dismutase (SOD) and catalase (CAT) activities than wild type (WT) under drought stress. Overexpression of TaASR1 in tobacco also enhanced the expression of ROS-related and stress-responsive genes under osmotic stress. In addition, transgenic lines exhibited improved tolerance to oxidative stress by retaining more effective antioxidant system. Finally, TaASR1 was localized in the cell nucleus and functioned as a transcriptional activator. Taken together, our results showed that TaASR1 functions as a positive factor under drought/osmotic stress, involved in the regulation of ROS homeostasis by activating antioxidant system and transcription of stress-associated genes.

MAPK cascades are universal signal transduction modules and play important roles in plant growth, development and in response to a variety of biotic and abiotic stresses. Although MAPKs and MAPKKs have been systematically investigated in several plant species including Arabidopsis, rice and poplar, no systematic analysis has been conducted in the emerging monocot model plant Brachypodium distachyon. In the present study, a total of 16 MAPK genes and 12 MAPKK genes were identified from B. distachyon. An analysis of the genomic evolution showed that both tandem and segment duplications contributed significantly to the expansion of MAPK and MAPKK families. Evolutionary relationships within subfamilies were supported by exon-intron organizations and the architectures of conserved protein motifs. Synteny analysis between B. distachyon and the other two plant species of rice and Arabidopsis showed that only one homolog of B. distachyon MAPKs was found in the corresponding syntenic blocks of Arabidopsis, while 13 homologs of B. distachyon MAPKs and MAPKKs were found in that of rice, which was consistent with the speciation process of the three species. In addition, several interactive protein pairs between the two families in B. distachyon were found through yeast two hybrid assay, whereas their orthologs of a pair in Arabidopsis and other plant species were not found to interact with each other. Finally, expression studies of closely related family members among B. distachyon, Arabidopsis and rice showed that even recently duplicated representatives may fulfill different functions and be involved in different signal pathways. Taken together, our data would provide a foundation for evolutionary and functional characterization of MAPK and MAPKK gene families in B. distachyon and other plant species to unravel their biological roles.