[Association of the -c.108C>T and c.192Q>R polymorphisms of the PON1 gene with preeclampsia among Chinese women].

OBJECTIVE: To assess the association of -c.108C>T and c.192Q>R polymorphisms of paraoxonase 1 (PON1) gene with preeclampsia (PE) and the influence of genotypes on the metabolic and oxidative stress indexes among Chinese women. METHODS: This case-control study has included 334 patients with PE and 1337 healthy pregnant women. The -c.108C>T and c.192Q>R genotypes were determined by PCR and restriction fragment length polymorphism method. Metabolic and oxidative stress parameters were also analyzed. RESULTS: No statistical difference in the genotypic and allelic frequencies for the -c.108C>T and c.192Q>R polymorphisms of the PON1 gene was found between the PE patients and the healthy controls (P > 0.05). Nevertheless, the 192Q-108T haplotype of these polymorphisms was associated with an increased risk of PE (P = 0.007). Total antioxidant capacity (TAC) and atherosderosis index were higher in patients with the -108TT genotype compared with those with a CT genotype (P < 0.05); whilst total oxidant status was lower in patients with a CT genotype compared with those with a CC genotype (P = 0.036). Malondialdehyde level was higher in patients with a 192RR genotype compared with those with a QQ genotype (P = 0.019). TAC level was higher in patients with a RR genotype compared with those with a QR genotype (P = 0.015). CONCLUSION: The 192Q-108T haplotype of the PON1 gene is associated with the risk for PE. These polymorphisms may be associated with abnormal lipid metabolism and oxidative stress among Chinese PE patients.

Construction of Dome-Shaped 3D Corneal Epithelial Tissue Models Based on Eyeball-Shaped Gel Microspheres.

By overcoming interspecies differences and mimicking the in vivo microenvironment, three-dimensional (3D) in vitro corneal models have become a significant novel tool in contemporary ophthalmic disease research. However, existing 3D corneal models struggle to replicate the actual human corneal environment, especially the dome-shaped physiological structure with adjustable curvature. Addressing these challenges, this study introduces a straightforward method for fabricating collagen/chitosan-alginate eyeball-shaped gel microspheres with a Janus structure via a two-phase aqueous system, used subsequently to construct in vitro 3D corneal epithelial tissue models. By adjusting the diameter ratio of collagen/chitosan to alginate droplets, we can create eyeball-shaped gel microspheres with varying curvatures. Human corneal epithelial cells were seeded on the surfaces of these microspheres, leading to the formation of in vitro 3D corneal epithelial tissues characterized by dome-like multilayers and tight junctions. Additionally, the model demonstrated responsiveness to UVB exposure through the secretion of reactive oxygen species (ROS) and proinflammatory factors. Therefore, we believe that in vitro 3D corneal epithelial tissue models with dome-shaped structures hold significant potential for advancing ophthalmic research.

Indomethacin Combined with Ciprofloxacin Improves the Prognosis of Mice under Severe Traumatic Infection via the PI3K/Akt Pathway in Macrophages.

The prevention and treatment strategies for traumatic infection often focus on the use of antibiotics, while eschew the combined treatment of the bacteria, their toxins, and inflammatory mediators. This might be a main reason the prognosis of wound victims has not improved. Although our previous work found that the combination of indomethacin (IND) and ciprofloxacin (CIP) could promote skin wound repair and enhance the immune function, the efficacy and safety of this strategy for severe traumatic infection-mediated complications remain unknown. Additionally, there is no study on the relevant target cells and molecular mechanisms. In this study, C57BL/6 adult male mice were modeled for severe traumatic infection, and the optimal doses of IND and CIP alone were determined. After that, the efficacy and safety of IND plus CIP in traumatic infection mice were explored. Then the differentially expressed genes of activated macrophages in this process were analysed and verified by transcriptomic methods and conventional experimental techniques. The role of a candidate signalling pathway (PI3K/Akt) in regulating macrophage function and drug combination therapy was evaluated. The results showed that IND plus CIP increased the survival rate, reduced the degree of inflammatory response, and enhanced the bacteriostatic effect in mice under traumatic infection. This combined therapy did not cause significant damage to the functions of important organs (liver, kidney, heart). In addition, IND combined with CIP induced macrophages to significantly change their expression levels of several cytokines, including interleukin (IL) -1ß, IL-6, IL-10, IL-22, IL-23A, IL-17A, IL-17F, cluster of differentiation (CD) 11b and other genes/encode proteins. Further study showed that intervention with the PI3K inhibitor LY294002 modulated the secretion function of the above-mentioned macrophages and Akt activation (phosphorylation at serine 473). IND plus CIP can regulate macrophage function through the PI3K/Akt signalling pathway and improve the prognosis of severe traumatic infected mice. This may be a new therapeutic strategy for the prevention and treatment of severe traumatic infection.

Heme oxygenase 2 genetic variants alter hormonal and metabolic traits in polycystic ovary syndrome.

Oxidative stress and metabolic disorders are involved in the pathogenesis of polycystic ovary syndrome (PCOS). Heme oxygenase 2 (HMOX2) plays a critical role in preserving heme metabolism as well as in modulating glycolipid metabolism, oxidative stress, and inflammation. This study examined the correlation between HMOX2 G554A (rs1051308) and A-42G (rs2270363) genetic variants with the risk of PCOS and assessed the effects of these genotypes on clinical, hormonal, metabolic, and oxidative stress indices using a case-control design that included 1014 patients with PCOS and 806 control participants. We found that the allelic and genotypic frequencies of the HMOX2 G554A and A-42G polymorphisms were comparable between the PCOS and control groups in Chinese women (P > 0.05). Nevertheless, it was discovered that patients with the AA or AG genotype of A-42G polymorphism had notably elevated levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo)B, and/or apoB/apoA1 ratio than those with the GG genotypes (P < 0.05). Patients with the GG or AG genotype of G554A polymorphism had elevated serum levels of LH, FSH, E2, LH/FSH ratio, TC, HDL-C, LDL-C, apoB, and/or apoB/apoA1 ratio and lower 2-h glucose concentration compared with those with the AA genotype (P < 0.05). Our findings indicate a potential association between the genetic variants and endocrine abnormalities in the reproductive system and metabolic irregularities in glycolipid levels in patients, thus suggesting their potential role in the pathogenesis of PCOS.

[Study on injury parameters of severe blast injury in mice at plain and plateau based on equivalent trauma].

OBJECTIVE: To explore the establishment of the interconvertible injury parameters of same severe blast injury in mice at plain and plateau. METHODS: A total of 157 C57BL/6 male mice were randomly divided into plain control group (8 mice), plain injury group (77 mice), plateau control group (8 mice) and plateau injury group (64 mice) according to random number table method. The mice in plateau control group and plateau blast injury group had been placed in animal experimental low-pressure oxygen chamber to simulate 4 000 meters plateau environment for 5 days in advance. Then the mice in plain blast injury group and plateau blast injury group were put into biological shock tube, respectively. Different pressures of the driving section were selected to establish the severe blast injury models in mice at plain and 4 000 meters plateau to reach approximately 70% mortality within 72 hours. The equivalent traumatic condition at 24 hours after blast injury in different groups was verified by the series of experiments including gross autopsy, lung wet/dry weight ratio (W/D), hematoxylin-eosin (HE) staining and histological scoring. RESULTS: The mice mortality were basically consistent between the plain injury group (65%) and plateau injury group (75%) when 5.4 MPa and 4.0 MPa of the driving section pressures were chosen, respectively. Compared with the corresponding control groups, the lungs showed massive hemorrhage (patchy and diffuse) with significant pulmonary edema in both plain 5.4 MPa-injured group and the plateau 4.0 MPa-injured group at 24 hours after blast injury. Compared with the plateau control group, the pulmonary W/D ratio were significantly increased in the plateau injury group (5.579±0.646 vs. 4.476±0.076, P < 0.05), while the difference between plateau injury group and the plain control group was not statistically significant (5.303±1.020 vs. 4.015±0.144, P > 0.05). Also, compared with the corresponding control groups, the analysis of lung histopathological sections showed that there were several pathological changes including large alveolar rupture and fusion, thickened alveolar walls, and a small amount of inflammatory cell infiltration in the alveolar lumen in the groups of plain 5.4 MPa and plateau 4.0 MPa. In addition, the histopathological scores of lung in the groups of plain 5.4 MPa and plateau 4.0 MPa were significantly higher than that in corresponding control group (8.67±0.82 vs. 1.67±0.52, 9.00±1.10 vs. 2.17±0.41, both P < 0.05), however, there was no statistical difference for the above score between plain blast injury group and plateau blast injury group. CONCLUSIONS: The pressures of driving section 5.4 MPa and 4.0 MPa are injury parameters to establish equivalent severe blast injury in mice at plain and plateau, respectively, which can be converted to each other. This study provides support for the application and evaluation of prevention and treatment technology for severe blast injury in special environment.

Genomic insights into historical improvement of heterotic groups during modern hybrid maize breeding.

Single-cross maize hybrids display superior heterosis and are produced from crossing two parental inbred lines belonging to genetically different heterotic groups. Here we assembled 1,604 historically utilized maize inbred lines belonging to various female heterotic groups (FHGs) and male heterotic groups (MHGs), and conducted phenotyping and genomic sequencing analyses. We found that the FHGs and MHGs have undergone both convergent and divergent changes for different sets of agronomic traits. Using genome-wide selection scans and association analyses, we identified a large number of candidate genes that contributed to the improvement of agronomic traits of the FHGs and MHGs. Moreover, we observed increased genetic differentiation between the FHGs and MHGs across the breeding eras, and we found a positive correlation between increasing heterozygosity levels in the differentiated genes and heterosis in hybrids. Furthermore, we validated the function of two selected genes and a differentiated gene. This study provides insights into the genomic basis of modern hybrid maize breeding.

The combination of ciprofloxacin and indomethacin suppresses the level of inflammatory cytokines secreted by macrophages in vitro.

PURPOSE: The combined use of antibiotics and anti-inflammatory medicine to manage bacterial endotoxin-induced inflammation following injuries or diseases is increasing. The cytokine level produced by macrophages plays an important role in this treatment course. Ciprofloxacin and indomethacin, two typical representatives of antibiotics and anti-inflammatory medicine, are cost-effective and has been reported to show satisfactory effect. The current study aims to investigate the effect of ciprofloxacin along with indomethacin on the secretion of inflammatory cytokines by macrophages in vitro. METHODS: Primary murine peritoneal macrophages and RAW 264.7 cells were administrated with lipopolysaccharide (LPS) for 24 h. The related optimal dose and time point of ciprofloxacin or indomethacin in response to macrophage inflammatory response inflammation were determined via macrophage secretion induced by LPS. Then, the effects of ciprofloxacin and indomethacin on the secretory functions and viability of various macrophages were determined by enzyme-linked immunosorbent assay and flow cytometry analysis, especially for the levels of interleukin (IL)-1ß, IL-6, IL-10, and tumor necrosis factor (TNF)-α. The optimal dose and time course of ciprofloxacin affecting macrophage inflammatory response were determined by testing the maximum inhibitory effect of the drugs on pro-inflammatory factors at each concentration or time point. RESULTS: According to the levels of cytokines secreted by various macrophages (1.2 × 106 cells/well) after administration of 1 µg/mL LPS, the optimal dose and usage timing for ciprofloxacin alone were 80 µg/mL and 24 h, respectively, and the optimal dose for indomethacin alone was 10 µg/mL. Compared with the LPS-stimulated group, the combination of ciprofloxacin and indomethacin reduced the levels of IL-1ß (p < 0.05), IL-6 (p < 0.05), IL-10 (p < 0.01)), and TNF-α (p < 0.01). Furthermore, there was greater stability in the reduction of inflammatory factor levels in the combination group compared with those in which only ciprofloxacin or indomethacin was used. CONCLUSION: The combination of ciprofloxacin and indomethacin suppressed the levels of inflammatory cytokines secreted by macrophages in vitro. This study illustrates the regulatory mechanism of drug combinations on innate immune cells that cause inflammatory reactions. In addition, it provides a new potential antibacterial and anti-inflammatory treatment pattern to prevent and cure various complications in the future.

Endothelialization strategy of implant materials surface: The newest research in recent 5 years.

In recent years, more and more metal or non-metal materials have been used in the treatment of cardiovascular diseases, but the vascular complications after transplantation are still the main factors restricting the clinical application of most grafts, such as acute thrombosis and graft restenosis. Implant materials have been extensively designed and surface optimized by researchers, but it is still too difficult to avoid complications. Natural vascular endodermis has excellent function, anti-coagulant and anti-intimal hyperplasia, and it is also the key to maintaining the homeostasis of normal vascular microenvironment. Therefore, how to promote the adhesion of endothelial cells (ECs) on the surface of cardiovascular materials to achieve endothelialization of the surface is the key to overcoming the complications after implant materialization. At present, the surface endothelialization design of materials based on materials surface science, bioactive molecules, and biological function intervention and feedback has attracted much attention. In this review, we summarize the related research on the surface modification of materials by endothelialization in recent years, and analyze the advantages and challenges of current endothelialization design ideas, explain the relationship between materials, cells, and vascular remodeling in order to find a more ideal endothelialization surface modification strategy for future researchers to meet the requirements of clinical biocompatibility of cardiovascular materials.

[Cultivation of college students' innovative and entrepreneurial thinking and ability based on Synthetic Biology and iGEM].

Synthetic Biology is one of the most promising fields of modern Biology and a frontier interdisciplinary subject in the 21st century. With the rapid development of synthetic biology, the International Genetically Engineered Machine (iGEM) competition has emerged. The iGEM competition, based on the subject foundation of Synthetic Biology, intends to solve the biological problems in our daily life by applying modern biological technology. In recent years, with the continuous increase of participating teams, the iGEM competition has received extensive attention and achieved great progress. On the basis of the development of Synthetic Biology, we analyzed the 2018-2020 award-winning projects of the iGEM competition and illustrated the role and significance of the iGEM competition in cultivating college students' innovative thinking and ability with the participation experience of the iGEM team of Southwest Jiaotong University as an example.

Identification of Pyruvate Carboxylase as the Cellular Target of Natural Bibenzyls with Potent Anticancer Activity against Hepatocellular Carcinoma via Metabolic Reprogramming.

Cancer cell proliferation in some organs often depends on conversion of pyruvate to oxaloacetate via pyruvate carboxylase (PC) for replenishing the tricarboxylic acid cycle to support biomass production. In this study, PC was identified as the cellular target of erianin using the photoaffinity labeling-click chemistry-based probe strategy. Erianin potently inhibited the enzymatic activity of PC, which mediated the anticancer effect of erianin in human hepatocellular carcinoma (HCC). Erianin modulated cancer-related gene expression and induced changes in metabolic intermediates. Moreover, erianin promotes mitochondrial oxidative stress and inhibits glycolysis, leading to insufficient energy required for cell proliferation. Analysis of 14 natural analogs of erianin showed that some compounds exhibited potent inhibitory effects on PC. These results suggest that PC is a cellular target of erianin and reveal the unrecognized function of PC in HCC tumorigenesis; erianin along with its analogs warrants further development as a novel therapeutic strategy for the treatment of HCC.

[Clinical Study of the Impact of ACE I/D Gene Variation on the Clinical Parameters of Patients with Polycystic Ovary Syndrome].

OBJECTIVE: To investigate the relationship between angiotensin Ⅰ-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the genetic risks for polycystic ovary syndrome (PCOS) and to evaluate the impact of ACE I/D genotypes on clinical, hormonal, metabolic and oxidative stress parameters in patients with PCOS. METHODS: This was a retrospective case-control study involving a total of 1 020 PCOS patients and 825 female controls who visited the outpatient clinic of the Department of Reproductive Endocrinology, West China Second Hospital of Sichuan University between 2006 and 2019. The ages of the subjects ranged between 17 and 44. The ACE I/D genotypes were determined by polymerase chain reaction (PCR) and gel electrophoresis. 667 PCOS patients and 527 controls were selected for an analysis of their genotypes and the hormonal, metabolic and oxidative stress parameters. RESULTS: The genotype distributions of the ACE I/D single nucleotide polymorphism was in Hardy-Weinberg equilibrium in both the PCOS group and the control group (all P>0.05), which was representative of the population. There were no statistically significant differences in genotype and allele frequencies between the PCOS and the control groups ( P>0.05). After adjusting for both age and body mass index (BMI), there was no statistically significant difference in clinical characteristics among all genotypes in either the PCOS group or the control group. In the PCOS group, compared with the II genotype subgroup, the ID genotype subgroup had lower luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, while the DD genotype subgroup had higher homeostatic model assessment of insulin resistance (HOMA-IR) and malondialdehyde (MDA) levels. Compared with the ID genotype subgroup, the DD genotype subgroup had lower serum sex hormone binding globulin (SHBG) level, but higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels ( P<0.05). In the control group, II genotype subgroup had a higher level of total oxidant status (TOS) than that of the DD genotype subgroup. CONCLUSION: ACE I/D genetic polymorphism is not associated with risks for PCOS. The I/D variation of ACE gene may be related to insulin resistance, dyslipidaemia, hyperandrogenemia and oxidative stress in PCOS patients.

Oxidative stress promotes hyperandrogenism by reducing sex hormone-binding globulin in polycystic ovary syndrome.

OBJECTIVE: To determine the relationships between circulating sex hormone-binding globulin (SHBG) and oxidized low-density lipoprotein (ox-LDL), total oxidant status, total antioxidant capacity, oxidative stress index, malondialdehyde, and the high-density lipoprotein (HDL) inflammatory index in patients with polycystic ovary syndrome (PCOS) and to investigate the effect of oxidative stress on the expression of SHBG and its mechanism in HepG2 cells. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENT(S): A total of 533 women with PCOS and 292 control women were included. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Circulating SHBG, hormones, and metabolic and oxidative stress indices were determined in all subjects. The effects of ox-LDL and ox-HDL on the mRNA and protein expression of SHBG and related transcription factors were observed in HepG2 cells. RESULT(S): The HDL inflammatory index, total oxidant status, oxidative stress index, and malondialdehyde levels were significantly higher in the three PCOS subgroups with different SHBG levels than in the controls. The ox-LDL and total antioxidant capacity were higher in the PCOS subgroups with SHBG levels <75th percentile compared with the controls or the PCOS subgroup with SHBG levels ≥75th percentile. In HepG2 cells, the SHBG concentration in the culture supernatant, the mRNA levels of SHBG and hepatocyte nuclear factor-4α (HNF-4α), and the protein levels of HNF-4α were significantly lower in ox-LDL- and ox-HDL-treated cells than in the control cells and lipoprotein-treated cells. CONCLUSION(S): Oxidative stress inhibits the expression and secretion of SHBG by downregulating HNF-4α in vitro and may be an important factor promoting the occurrence of hyperandrogenemia in PCOS.

Myeloperoxidase and CYBA genetic variants in polycystic ovary syndrome.

BACKGROUND: Oxidative stress plays a pivotal role in the pathogenesis of polycystic ovary syndrome (PCOS). Genetic variations in myeloperoxidase (MPO; G-463A) and NADPH oxidase p22phox subunit (CYBA; C242T) cause inter-individual variability in enzyme activities. Here, we investigated the associations between MPO activity and the MPO G-463A and CYBA C242T polymorphisms in Chinese women with PCOS. METHODS: This case-control study included 1003 patients with PCOS and 810 controls. The G-463A and C242T polymorphisms were detected by polymerase chain reaction and restriction analysis, and clinical, hormonal, metabolic and oxidative stress parameters and MPO activity were analysed. RESULTS: The frequencies of the GA + AA genotype and A allele frequency of the MPO G-463A polymorphism were significantly higher in the PCOS group than in the control group. Logistic regression analysis showed that the MPO-463A allele is a risk factor for PCOS (OR = 1.261, 95% CI: 1.042-1.526, P = .017). Patients with the AA genotype tended to have higher plasma MPO activity than those with the GG genotype. No statistical significance was found in the genotype and allele frequencies of the CYBA C242T polymorphism between the PCOS and control groups. However, we demonstrated that the coexistence of the MPO A allele (GA + AA genotypes) and the CYBA CC genotype was associated with an increased risk of PCOS when compared with the wild-type GG/CC genotypes (OR = 1.302, 95% CI: 1.030-1.646, P = .027). CONCLUSION: The MPO G-463A variant, but not CYBA C242T variant, is associated with a risk of PCOS in Chinese women.

[Analysis of rs4420638A/G and -317H1/H2 polymorphisms of APOC1 gene among Chinese patients with pre-eclampsia].

OBJECTIVE: To assess the association of apolipoprotein (apo) C1 (APOC1) gene rs4420638A/G and -317H1/H2 polymorphisms with the risk of pre-eclampsia (PE) and the influence of their genotypes on the clinical and metabolic indexes among Chinese women. METHODS: In total 289 PE patients and 824 women with uncomplicated pregnancies were included. The rs4420638A/G genotype was determined by a Taqman real-time PCR allelic discrimination assay. The -317H1/H2 genotype was measured through PCR and restriction fragment length polymorphism analysis. Serum lipid and apo levels were measured by an enzymatic kit and a PEG-enhanced immunoturbidimetric assay. RESULTS: Allelic and genotypic frequencies of the APOC1 gene rs4420638A/G and -317H1/H2 were not significantly different between the two groups (all P> 0.05). However, patients carrying the G allele of the rs4420638A/G locus had higher serum levels of triglyceride, non-HDL-C and apoB, and a higher apoB/apoA1 ratio compared with those with an AA genotype (all P< 0.05). Patients carrying the H2 allele of the -317H1/H2 polymorphism had smaller delivery gestational weeks compared with those with the H1H1 genotype (P< 0.05). CONCLUSION: Polymorphisms of the APOC1 gene rs4420638 and -317H1/H2 sites may be associated with abnormal lipoprotein metabolism among Chinese patients with PE, though no association was found between variants of the APOC1 gene and the risk of PE among them.

Musculin Deficiency Aggravates Colonic Injury and Inflammation in Mice with Inflammatory Bowel Disease.

Intestinal inflammatory reactions and resulting tissue injuries are two major aspects of inflammatory bowel disease (IBD). The regulatory factors involved in the pathogenesis of IBD remain unclear. Recent studies showed that musculin (MSC) as a transcription suppressor participates in the regulation of certain immune functions. The purpose of this study was to determine the impact of MSC deficiency on colonic injury and inflammatory reaction under IBD, where wild-type (WT, +/+) and MSC-knockout (MSCKO, MSC-/-) mice were induced for disease by dextran sulfate sodium (DSS) in drinking water. Immunohistochemistry hematoxylin-eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), and quantitative real-time polymerase chain reaction (qRT-PCR) were used to analyze the matching samples from groups of different genotypes. The colonic epithelial injury in the MSC-/- IBD group was much severer than that in the +/+ IBD group, concurrent with higher IL-22 levels from the supernatant of ex vivo cultured colon tissues in the MSC-/- IBD group than those in the +/+ IBD group. The mRNA levels of IL-22 in mesenteric lymph nodes (MLN) also manifested similar tendency. MSC deficiency may enhance the inflammatory reactions in the gut via excessive secretion of IL-22, leading to aggravated colonic epithelial injury under IBD.

Association of GPx1 P198L and CAT C-262T Genetic Variations With Polycystic Ovary Syndrome in Chinese Women.

Background: Oxidative stress plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). Glutathione peroxidase 1 (GPx1) and catalase (CAT) are the major intracellular antioxidant enzymes that can detoxify hydrogen peroxide into water, preventing cellular injury from reactive oxygen species. The aim of the present study was to investigate the association of GPx1 P198L (Pro198Leu, C559T, rs1050450) and CAT C-262T (rs1001179) genetic polymorphisms with the risk of PCOS and evaluate the effects of the genotypes on clinical, hormonal, metabolic and oxidative stress parameters in Chinese women. Methods: This is a case-control study of 654 patients with PCOS and 535 controls. The GPx1 P198L, CAT C-262T, and superoxide dismutase 2 (SOD2) A16V genotypes were determined by polymerase chain reaction amplification and restriction analysis. Clinical, hormonal, metabolic and oxidative stress parameters were also analyzed. Results: The frequencies of the PL + LL genotype (14.1 vs. 8.4%) and L allele (7.3 vs. 4.4%) of GPx1 P198L polymorphism were significantly higher in patients with PCOS than in control subjects. Genotype (PL + LL) remained a significant predictor for PCOS in prognostic models including age, body mass index (BMI), insulin resistance index, total cholesterol, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol as covariates (OR = 2.105, 95%CI: 1.330-3.331, P = 0.001). Patients carrying the L allele had relatively high average ovarian volume, waist circumference, and malondialdehyde levels (P < 0.07) compared with patients with the PP genotype. We also demonstrated that the subjects with both GPx1 L and SOD2 A alleles further increase the risk of PCOS compared with the individuals carrying the PP/VV genotype after adjusting for age and BMI (OR = 5.774, 95%CI: 2.243-14.863, P < 0.001). However, no significant differences were observed in the frequencies of the CAT C-262T genotypes and alleles between PCOS and control groups. Conclusions: The GPx1 P198L, but not CAT C-262T, genetic polymorphism is associated with the risk of PCOS in Chinese women.

Comprehensive Analysis of Differentially Expressed Unigenes under NaCl Stress in Flax (Linum usitatissimum L.) Using RNA-Seq.

Flax (Linum usitatissimum L.) is an important industrial crop that is often cultivated on marginal lands, where salt stress negatively affects yield and quality. High-throughput RNA sequencing (RNA-seq) using the powerful Illumina platform was employed for transcript analysis and gene discovery to reveal flax response mechanisms to salt stress. After cDNA libraries were constructed from flax exposed to water (negative control) or salt (100 mM NaCl) for 12 h, 24 h or 48 h, transcription expression profiles and cDNA sequences representing expressed mRNA were obtained. A total of 431,808,502 clean reads were assembled to form 75,961 unigenes. After ruling out short-length and low-quality sequences, 33,774 differentially expressed unigenes (DEUs) were identified between salt-stressed and unstressed control (C) flax. Of these DEUs, 3669, 8882 and 21,223 unigenes were obtained from flax exposed to salt for 12 h (N1), 24 h (N2) and 48 h (N4), respectively. Gene function classification and pathway assignments of 2842 DEUs were obtained by comparing unigene sequences to information within public data repositories. qRT-PCR of selected DEUs was used to validate flax cDNA libraries generated for various durations of salt exposure. Based on transcriptome sequences, 1777 EST-SSRs were identified of which trinucleotide and dinucleotide repeat microsatellite motifs were most abundant. The flax DEUs and EST-SSRs identified here will serve as a powerful resource to better understand flax response mechanisms to salt exposure for development of more salt-tolerant varieties of flax.

QTL Mapping of Fiber-Related Traits Based on a High-Density Genetic Map in Flax (Linum usitatissimum L.).

A genetic map is an important and valuable tool for quantitative trait locus (QTL) mapping, marker-assisted selection (MAS)-based breeding, and reference-assisted chromosome assembly. In this study, 112 F2 plants from a cross between Linum usitatissimum L. "DIANE" and "NY17" and parent plants were subjected to high-throughput sequencing and specific-locus amplified fragment (SLAF) library construction. After preprocessing, 61.64 Gb of raw data containing 253.71 Mb paired-end reads, each 101 bp in length, were obtained. A total of 192,797 SLAFs were identified, of which 23,115 were polymorphic, with a polymorphism rate of 11.99%. Finally, 2,339 SLAFs were organized into a linkage map consisting of 15 linkage groups (LGs). The total length of the genetic map was 1483.25 centimorgans (cM) and the average distance between adjacent markers was 0.63 cM. Combined with flax chromosome-scale pseudomolecules, 12 QTLs associating with 6 flax fiber-related traits were mapped on the chromosomal scaffolds. This high-density genetic map of flax should serve as a foundation for flax fine QTL mapping, draft genome assembly, and MAS-guided breeding. Ultimately, the genomic regions identified in this research could potentially be valuable for improving flax fiber cultivars, as well as for identification of candidate genes involved in flax fiber formation processes. SIGNIFICANCE STATEMENT: A high-density genetic map of flax was constructed, and QTLs were identified on the sequence scaffolds to be interrelated with fiber-related traits. The results of this study will not only provide a platform for gene/QTL fine mapping, map-based gene isolation, and molecular breeding for flax, but also provide a reference to help position sequence scaffolds on the physical map and assist in the process of assembling the flax genome sequence.

Genome re-sequencing analysis uncovers pathogenecity-related genes undergoing positive selection in Magnaporthe oryzae.

Rice blast caused by Magnaporthe oryzae (M. oryzae) is one of the most destructive diseases, which causes significant rice yield losses and affects global food security. To better understand genetic variations among different isolates of M. oryzae in nature, we re-sequenced the genomes of two field isolates, CH43 and Zhong-10-8-14, which showed distinct pathogenecity on most of the rice cultivars. Genome-wide genetic variation analysis reveals that ZHONG-10-8-14 exhibits higher sequence variations than CH43. Structural variations (SVs) detection shows that the sequence variations primarily occur in exons and intergenic regions. Bioinformatics analysis for gene variations reveals that many pathogenecity-related pathways are enriched. In addition, 193 candidate effectors with various DNA polymorphisms were identified, including two known effectors AVR-Pik and AVR-Pita1. Comparative polymorphism analysis of thirteen randomly selected effectors suggests that the genetic variations of effectors are under positive selection. The expression pattern analysis of several pathogenecity-related variant genes indicates that these genes are differentially regulated in two isolates, with much higher expression levels in Zhong-10-8-14 than CH43. Our data demonstrate that the genetic variations of effectors and pathogenecity-related genes are under positive selection, resulting in the distinct pathogenicities of CH43 and Zhong-10-8-14 on rice.

Peripheral blood nerve growth factor levels in major psychiatric disorders.

Nerve growth factor (NGF) plays crucial roles in promoting neural growth and survival, and mediating synaptic and morphological plasticity. Several studies investigated the correlation between peripheral NGF levels and major psychiatric disorders, including schizophrenia (SCZ), major depressive disorder (MDD) and bipolar disorder (BPD); however, the findings were inconsistent. This meta-analysis sought to investigate blood NGF levels in patients with psychiatric disorders compared with healthy subjects and examined potential effects of blood fraction, medication and disease status. A total of 21 eligible studies, encompassing 1342 patients suffering from psychiatric disorders and 1225 healthy subjects, were enrolled in the present meta-analysis. No obvious publication bias was observed either for SCZ, MDD or BPD by the Begg's test (P > 0.05). Random-effects meta-analysis showed that SCZ (Z = 2.14, P = 0.033, SMD = -1.08, 95% CI = -2.07 to -0.09) and MDD (Z = 2.57, P = 0.010, SMD = -0.61, 95% CI = -1.08 to -0.14) patients had significantly reduced NGF levels, compared with healthy controls. Notably, this decrease was enhanced in un-medicated patients of SCZ (P = 0.004) and medicated or chronic patients of MDD (P < 0.001). No significant difference of NGF levels was observed between BPD patients and controls (P > 0.05). These results supported an association between the reduction of NGF levels and psychiatric disorders. It remains unclear whether the change of NGF levels is a prerequisite for its function in psychiatric disorders development or merely an epiphenomenon unrelated to the pathophysiologic mechanisms.