YTHDF1's Regulatory Involvement in Breast Cancer Prognosis, Immunity, and the ceRNA Network.

YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), an m6A reader, has a role in the development and progression of breast cancer as well as the immunological microenvironment. The networks of competing endogenous RNA in cancer have received much attention in research. In tumor gene therapy, the regulatory networks of m6A and competing endogenous RNA are increasingly emerging as a new route. We evaluated the relationship between the YTHDF1 expression, overall survival, and clinicopathology of breast cancer using TCGA, PrognoScan, and other datasets. We used Western blot to demonstrate that YTHDF1 is substantially expressed in breast cancer tissues. Furthermore, we explored YTHDF1's functions in the tumor mutational burden, microsatellite instability, and tumor microenvironment. Our findings indicate that YTHDF1 is a critical component of the m6A regulatory proteins in breast cancer and may have a particular function in the immunological microenvironment. Crucially, we investigated the relationship between YTHDF1 and the associated competitive endogenous RNA regulatory networks, innovatively creating three such networks (Dehydrogenase/Reductase 4-Antisense RNA 1-miR-378g-YTHDF1, HLA Complex Group 9-miR-378g-YTHDF1, Taurine Up-regulated 1-miR-378g-YTHDF1). Furthermore, we showed that miR-378g could inhibit the expression of YTHDF1, and that miR-378g/YTHDF1 could impact MDA-MB-231 proliferation. We speculate that YTHDF1 may serve as a biomarker for poor prognosis and differential diagnosis, impact the growth of breast cancer cells via the ceRNA network axis, and be a target for immunotherapy against breast cancer.

Exosomal miRNAs assist in the crosstalk between tumor cells and immune cells and its potential therapeutics.

Exosomes are small extracellular vesicles that carry active substances (including proteins, lipids, and nucleic acids) and are essential for homeostasis and signal transmission. Recent studies have focused on the function of exosomal miRNAs in tumor progression. Researchers have expanded the use of exosomes and miRNAs as potential therapeutic tools and biomarkers to detect tumor progression. Immune cells, as an important part of the tumor microenvironment (TME), secrete a majority of exosome-derived miRNAs involved in the biological processes of malignancies. However, the underlying mechanisms remain unclear. Currently, there is no literature that systematically summarizes the communication of exosome-derived miRNAs between tumor cells and immune cells. Based on the cell specificity of exosome-derived miRNAs, this review provides the first comprehensive summary of the significant miRNAs from the standpoint of exosome sources, which are tumor cells and immune cells. Furthermore, we elaborated on the potential clinical applications of these miRNAs, attempting to propose existing difficulties and future possibilities in tumor diagnostics and therapy.

Tumor-derived Cav-1 promotes pre-metastatic niche formation and lung metastasis in breast cancer.

Rationale: Breast cancer (BC), as one of the most frequently diagnosed cancer, has a poor prognosis due to the development of distant metastasis. Among the BC metastatic sites, lung is one of the most common sites. Caveolin-1 (Cav-1) is a functional membrane protein that plays a vital role in tumor metastasis. Although studies have revealed that Cav-1 levels were elevated in patients with advanced cancer, whether Cav-1 affects BC lung metastasis by influencing the formation of pre-metastatic niche (PMN) through exosomes has not been explored. Methods: Differential ultracentrifugation, transmission electron microscopy and nanoparticle tracking analysis were used to verify the presence of exosomes. Transwell assays were used to examine the biological effects of exosomes containing Cav-1. Both in vitro cell cultures and mammary tumor cell-induced mouse models were used to assess the lung metastasis. The regulatory mechanisms of PMN formation were revealed using western blot, flow cytometry, RT-qPCR, immunofluorescence assays, gene overexpression assays and RNA interference assays. Results: Exosomes have critical functions in transporting Cav-1 between primary BC and metastatic organ microenvironments. Cav-1 in BC-derived exosomes can act as a signaling molecule to mediate intercellular communication and regulate the PMN before lung metastasis by regulating the expression of PMN marker genes and inflammatory chemokines in lung epithelial cells, promoting the secretion of tenascin-C (TnC) in lung fibroblasts to cause extracellular matrix (ECM) deposition, and inhibiting the PTEN/CCL2/VEGF-A signaling pathway in lung macrophages to facilitate their M2-type polarization and angiogenesis. Conclusion: Our study investigated the mechanisms of lung PMN formation induced by Cav-1 in BC-derived exosomes. Our data may provide new directions for exploring the mechanisms and developing treatment strategies of BC lung metastasis.

Influence of alternated drying and wetting on the characteristics of soil preferential flow formation in Honghe Arid Valley.

To clarify the effects of alternation of drying and wetting on the formation of soil preferential flow in arid valley, taking the wasteland in the arid valley of Honghe River as the research object, we analyzed the soil preferential flow characteristics before and after the simulation of drying and wetting alternation based on dyeing tracer method, water breakthrough curve, and image processing technology. The results showed that, under the simulated alternation of drying and wetting, the matrix flow occurred in the 0-10 cm soil layer, the dyeing depth reached 35 cm, the horizontal width of the preferred path was only 3-10 cm, and the dyeing area curve fluctuated little. Simulated alternation of drying and wetting led to significant increases in the steady effluent, macropores number, and macroporosity. In the 0-20 cm soil layer, the steady effluent after alternation of drying and wetting was about 0.27 cm3·s-1 higher than that non-alternation of drying and wetting, macropores number in dyeing area was about 1.4 times higher, and the macroporosity was 13.4% higher. The macropores number was positively correlated with stable flow rate. After simulated alternation of drying and wetting, the number of macropores from large to small was 0.6-0.8 mm＞0.8-1.0 mm＞1.0-1.5 mm＞1.5-2.0 mm＞2.0-3.7 mm, while under non-alternation of drying and wetting, it was 0.8-1.0 mm＞0.6-0.8 mm＞1.0-1.5 mm＞2.0-3.7 mm＞1.5-2.0 mm. The macropores number in each pore size range was significantly correlated with the dyeing area ratio. After simulated alternation of drying and wetting, the correlation increased, and the dominant factor affecting the occurrence of preferential flow changed from the macropores number in the pore size range of 1.5-2.0 mm to that of 0.8-1.0 mm. Therefore, the alternation of drying and wetting would affect the characteristics of macropores, which caused the soil to be more prone to preferential flow and with higher magnitude.

Voltine Ecotypes of the Asian Corn Borer and Their Response to Climate Warming.

In the Asian corn borer (ACB), Ostrinia furnacalis (Guenée), diapause is governed by a multigenetic constitution that responds to daylength and temperature with seasonality. The ACB displays uni- or multivoltinism, depending on its geographic specificity. Hence, warmer temperatures may result in alternation of voltinism in the ACB, which will help in understanding the ecological consequences of climate warming on insects. In the present study, we investigated the voltinism in two natural populations from Harbin (H) and Gongzhuling (G) as well as a laboratory (L) population (established from the H population in 2017) of the ACB, at ambient and elevated atmospheric CO2 (aCO2 390 µL/L and eCO2 750 µL/L) and temperature (aT and Et = At + 2 °C). From the diapause response, both the uni- and multivoltine ecotypes were coexisting in the H population. The neonate occurrence date of 50% individuals that induced diapause was ca. 10 days later in the G population than in the H population, but it was about 10 days earlier than in the L population. Comparing to the dates of onset and the peak of diapause induction, the G and L populations were less variable than the H population in response to a short and/or shortening daylength in the field. The univoltine individuals could not be eliminated completely after 19 generations of selection. Diapause incidence decreased with a climate-warming scenario, which was temporally specific and could be overridden by significantly low daily average temperatures. The eCO2 did not directly impact the voltinism. On the basis of voltinism, the H population was sympatric for uni- and multivoltine ecotypes, with multivoltinism being dominant. The univoltinism trait was recessive. Climate warming could significantly override the effect of photoperiod, which was yearly dependent. Warmer temperatures and a decreased latitude (shortened daylength), and their interaction, would drive ACB evolution toward diapause homogeneity for multivoltinism.

[Response of nutrient release and ecological stoichiometry of litter to simulated nitrogen deposition in evergreen broad-leaved forest in central Yunnan, China]. / æ»‡ä¸­å¸¸ç»¿é˜”å¶æž—å‡‹è½ç‰©å »åˆ†é‡Šæ”¾åŠç”Ÿæ€åŒ–å­¦è®¡é‡ç‰¹å¾å¯¹æ¨¡æ‹ŸN沉降的响应.

We examined nutrient release and ecological stoichiometric characteristics of litters under N deposition in an evergreen broadleaved forest in Mopan Mountain in central Yunnan. Nylon net bag method was used for in situ decomposition of leaf litter and twig litter. There were four treatments, including control (CK, 0 g N·m-2·a-1), low nitrogen (LN, 5 g N·m-2·a-1), medium nitrogen (MN, 15 g N·m-2·a-1), and high nitrogen (HN, 30 g N·m-2·a-1). The results showed that after one year of N addition, the contents of C and N in leaf litter, twig litter and soil increased gradually with the increases of N addition rates, with increases of 0.3%-8.2% and 4.9%-69.0%, respectively. C/N gradually decreased with increasing N addition rates, with a decrease of 0.8%-37.8%. There was no significant difference in P content, C/P and N/P of twig litter under different treatments. Treatment duration and N application rate significantly affected the N and P contents and stoichiometric ratios of leaf litter, twig litter and soil. During the 1-year decomposition process, the residual rates of C, N and P in litters were successively in the modes of release, leaching-enriched-released and leaching-enriched. Exogenous N addition significantly inhibited the release process of C, N and P in litter. The contents of C and P in soil were significantly positively correlated with the contents of N and P in litter, while the contents of N in soil were significantly positively correlated with the contents of C and N in litter. There was a significant correlation of stoichiometric characteristics between litter and soils of evergreen broadleaved forest under N deposition. Our results were helpful to understand the response mechanism of litter decomposition process of forest ecosystem to N deposition.

Preparation and characterization of curdlan/nanocellulose blended film and its application to chilled meat preservation.

In this study, to improve the mechanical and thermal properties of curdlan film, a curdlan/nanocellulose (NC) blended film was prepared and characterized for the first time. NC was successfully prepared from microcrystalline cellulose (MCC) with NaOH/urea treatment. The particle size of NC was observed to be 70-140 nm by cryo-electron microscope (cryo-EM). The blended film was prepared by adding the NC to curdlan solution. The tensile strength (TS) of the blended film reached the maximum value of 38.6 MPa, and the elongation at break (EB) was 40%. The DSC curve showed that the heat absorption peak of the film was 240 °C, indicating that the blended film has good temperature stability. Additionally, some other film properties were also improved, including gas barrier properties and transparency. Obvious morphological and molecular differences between the blended film and the pure curdlan film were discovered by SEM and FTIR analysis. Finally, the blended film was used for the preservation of chilled meat and extended the storage time of meat to 12 days. These results provided a theoretical basis for future application and development of biodegradable film.

Phylogenetic relationships and biological features reveal that male Ostrinia furnacalis (Lepidoptera: Crambidae) in Northeast China can be categorized into postmedial line-based clades.

Ostrinia furnacalis (Guenée) (Lepidoptera: Crambidae), often called the Asian corn borer, is a complicated pest because of its complex biological features, such as its adult dynamics, host choice, and life span. This complexity has been causing difficulties in both pest forecasting and control for more than 60 years. One likely explanation for this complexity is that O. furnacalis has several varieties that vary based on some specific features. During 2015-2017, postmedial line-based varieties of male O. furnacalis were identified as distinct clades (I, II, and III), which were then compared based on COI gene sequences, male sacculus construction, life span, male dynamics, and host preference. The results showed that: (1) clades II and III were more closely related to each other than Clade I, because they both completed two generations per year, more were captured in 2016 or fewer were captured in 2015, and they were more closely related according to phylogenetic inference; (2) all three clades shared some features, such as life spans under various rearing conditions, similar dynamic trends, and three teeth on the male sacculus; and (3) all three clades were significantly different from O. nubilalis based on genetic sequences, postmedial line pattern of the forewing, and sacculus construction. Overall, if O. furnacalis is categorized into clades, the species' features are likely to be a combination or mixture of the features of each individual clade. Our findings help explain the biological complexity of O. furnacalis. Future investigations on each individual clade are essential for improving forecasting and control of this pest.

[Effects of plant roots on soil preferential flow in typical forest and grassland in the dry-hot valley of Jinsha River, China]. / é‡‘æ²™æ±Ÿå¹²çƒ­æ²³è°·å ¸åž‹æž—è‰åœ°æ¤ç‰©æ ¹ç³»å¯¹åœŸå£¤ä¼˜å ˆæµçš„å½±å“.

To clarify the morphological characteristics of soil preferential flow and the effect of plant roots on its formation, plants from the typical vegetation types of an artificial woodland (Leucaena acacia) and a dry watershed grassland (Heteropogon contortus) of Yuanmou County, Jinsha River were selected as the experimental objects. Based on the staining and tracing method combined with Photoshop CS5 and the Image-Pro Plus 6.0 image processing technology, we analyzed the morphological and distribution characteristics of soil preferential flow under the two planting types and examined the effects of plant roots. We found significant difference in soil preferential flow dyeing area between the woodland and grassland species, and the overall variation trend of the forestland dyeing area ratio decreased with increasing soil depth. The dyeing area of the grassland decreased monotonously with the increases of soil depth. The occurrence degree of soil preferential flow in forest was higher than that of grassland. Root systemaffected the formation of soil preferential flow. At the root diameter ranges of 0≤d≤5 mm and d>10 mm, root length density of the woodland showed a monotonous decreasing trend with increasing soil depth, while in the root diameter range of 5 mm5 mm. The overall change trend of soil preferential flow dyeing area of two vegetation types in the study area decreased with increasing soil depth. Plant root system was closely related to the formation of soil preferential flow. Fine roots could promote while coarse roots may retard the formation of preferential flows.

[Responses of litter decomposition in two subalpine plantations to simulated nitrogen deposition in central Yunnan, China]. / 滇中亚高山人工林凋落物分解对模拟氮沉降的响应.

From February 2018 to January 2019, a field experiment of simulated nitrogen (N) depo-sition was conducted in Pinus armandii and Pinus yunnanensis plantations in the subalpine region of central Yunnan, China. The litterbag method was used for in situ litter (leaf and twig) decomposition experiment in both plantations. Four levels of N addition were applied, i.e., control (CK, 0 g N·m-2·a-1), low nitrogen (LN, 5 g N·m-2·a-1), medium nitrogen (MN, 15 g N·m-2·a-1), and high nitrogen (HN, 30 g N·m-2·a-1). The results showed that the annual decomposition rates of leaf and twig in P. armandii were 34.8% and 18.0%, which were higher than the 32.2% (leaf) and 16.1% (twig) in P. yunnanensis. Under N deposition, the LN treatment reduced the time of 95% mass loss of leaf and twig litter in P. armandii by 0.202 and 1.624 years, the MN treatment reduced by 0.045 and 1.437 years, and the HN treatment increased by 0.840 and 2.112 years, respectively. In the P. yunnanensis plantation, the LN treatment reduced the time of 95% mass loss of leaf and twig litter by 0.766 and 4.053 years, while the MN treatment increased by 0.366 and 0.455 years, and the HN treatment increased by 0.826 and 0.906 years, respectively. Litter (leaf and twig) decomposition of both P. armandii and P. yunnanensis were promoted by low N treatment and inhibited by high N treatment. The effects of N deposition on litter decomposition of two plantations were significantly correlated with the contents of cellulose and lignin in litter. In conclusion, the responses of litter decomposition to N deposition mainly depended on the litter substrate, especially cellulose and lignin contents.

Preparation of chitosan/curdlan/carboxymethyl cellulose blended film and its characterization.

In this study, to improve the thermal and mechanical properties of chitosan films, a chitosan/curdlan/carboxymethyl cellulose (CS/CD/CMC) ternary blended film was prepared and characterized. To prepare a uniform CS/CD/CMC ternary blended film, an effective method of blending CD with other materials was established as the following conditions: the ternary solution temperature was maintained at 60 °C, and the pH was controlled in the range from 12 to 4. Compared to the pure chitosan, the CS/CD/CMC blended films exhibited better mechanical properties, permeability, and thermal stability. In addition, visible light properties of the ternary blending film were improved. Scanning electron microscope and Fourier transform-infrared spectroscopy analyses indicated good compatibility among the CS, CD and CMC, which led to a corresponding improvement in the properties owing to interactions among the three components in the blending process. So, an effective method of blending CD with CS and CMC was established, and the blending film has good thermal and mechanical properties.

Expression profile analysis of maize in response to Setosphaeria turcica.

Northern corn leaf blight (NCLB), caused by the hemibiotrophic fungal pathogen Setosphaeria turcica, is one of the major foliar diseases of maize. The use of resistant cultivars is the most effective, economical, and environmentally friendly means to control NCLB. At present, the molecular mechanisms of maize resistance to S. turcica is not clear. Elucidating the molecular resistance mechanisms of maize response to S. turcica would aid breeding for a maize variety with fungal tolerance. In this study, maize leaves before and after infection with S. turcica were sequenced by RNA-seq, and 5903 differentially expressed genes (DEGs) were screened. Among them, 950 and 2245 genes were up-regulated 12 h and 60 h (samples H12 and H60, respectively) after infection, 752 and 1956 genes were down-regulated in H12 and H60, respectively. The GO and KEGG enrichment analysis of the DEGs showed that the GO and Pathway with the most annotation sequences were closely related to plant resistance. The expression of eight randomly selected DEGs was analyzed using qRT-PCR, and expression was consistent with the RNA-seq data. The expression patterns of four categories of genes were analyzed namely, genes involved in plant and pathogen interactions, transcription factors related to plant stress-tolerance, genes related to plant hormones and plant antioxidant. Many resistant signaling pathways were initiated such as the MAPK signal transduction pathway and the expression of multiple antioxidant-related genes [Peroxidase (POD), Catalase (CAT), Glutathione-S-transferase (GST) and Superoxide Dismutase (SOD)] following S. turcica infection. Many disease resistance signal transduction pathways and defense response pathways were induced following maize infection by S. turcica, suggesting a multiple gene network system. To the best of our knowledge, this is the first time that RNA-seq technology has been used to perform transcription analysis of maize in response to S. turcica stress. Taken together, these data provide novel and valuable information that will help understand the resistance mechanism in maize against S. turcica and locate candidate genes related to maize resistance against S. turcica.

Drug Repurposing Screen Identifies Foxo1-Dependent Angiopoietin-2 Regulation in Sepsis.

OBJECTIVE: The recent withdrawal of a targeted sepsis therapy has diminished pharmaceutical enthusiasm for developing novel drugs for the treatment of sepsis. Angiopoietin-2 is an endothelial-derived protein that potentiates vascular inflammation and leakage and may be involved in sepsis pathogenesis. We screened approved compounds for putative inhibitors of angiopoietin-2 production and investigated underlying molecular mechanisms. DESIGN: Laboratory and animal research plus prospective placebo-controlled randomized controlled trial (NCT00529139) and retrospective analysis (NCT00676897). SETTING: Research laboratories of Hannover Medical School and Harvard Medical School. PATIENTS: Septic patients/C57Bl/6 mice and human endothelial cells. INTERVENTIONS: Food and Drug Administration-approved library screening. MEASUREMENTS AND MAIN RESULTS: In a cell-based screen of more than 650 Food and Drug Administration-approved compounds, we identified multiple members of the 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor drug class (referred to as statins) that suppressed angiopoietin-2. Simvastatin inhibited 3-hydroxy-3-methyl-glutaryl-CoA reductase, which in turn activated PI3K-kinase. Downstream of this signaling, PI3K-dependent phosphorylation of the transcription factor Foxo1 at key amino acids inhibited its ability to shuttle to the nucleus and bind cis-elements in the angiopoietin-2 promoter. In septic mice, transient inhibition of angiopoietin-2 expression by liposomal siRNA in vivo improved absolute survival by 50%. Simvastatin had a similar effect, but the combination of angiopoietin-2 siRNA and simvastatin showed no additive benefit. To verify the link between statins and angiopoietin-2 in humans, we performed a pilot matched case-control study and a small randomized placebo-controlled trial demonstrating beneficial effects on angiopoietin-2. CONCLUSIONS: 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors may operate through a novel Foxo1-angiopoietin-2 mechanism to suppress de novo production of angiopoietin-2 and thereby ameliorate manifestations of sepsis. Given angiopoietin-2's dual role as a biomarker and candidate disease mediator, early serum angiopoietin-2 measurement may serve as a stratification tool for future trials of drugs targeting vascular leakage.

Expression of platelet-derived growth factor in the vascular walls of patients with lower extremity arterial occlusive disease.

The aim of the present study was to quantitatively analyze the expression of platelet-derived growth factor (PDGF)-A and PDGF-B in the vascular walls of patients with lower extremity arterial occlusive disease (LEAOD). The expression levels of PDGF-A and PDGF-B in the lower extremity arteries of 19 LEAOD patients (case group) and three healthy subjects (control group) was determined using quantitative polymerase chain reaction. Intergroup comparisons revealed that the relative mRNA expression levels were higher in the case group, as compared with the control group, for PDGF-A (34.38±5.80 vs. 21.94±1.05; P<0.05) and PDGF-B (33.95±5.92 vs. 24.15±3.12; P<0.05). In addition, the expression of PDGF-A revealed a positive linear correlation with the expression of PDGF-B (P<0.05). Therefore, the expression levels of PDGF-A and PDGF-B were found to be higher in the vascular walls of LEAOD patients, while the expression of PDGF-A was found to correlate with the expression of PDGF-B. A significant increase in the expression levlels of PDGF-A and PDGF-B were observed in the vascular walls of patients with LEAOD, and the expression of PDGF-A was associated with the expression of PDGF-B.

Comparison of γ-irradiation with other pretreatments followed with simultaneous saccharification and fermentation on bioconversion of microcrystalline cellulose for bioethanol production.

The effect of γ-irradiation pretreatment was compared with other pretreatment methods including ionic liquids (ILs), 1% HCl, 1% H2SO4, acidic aqueous Ils (AA-ILs), on the bioconversion efficiency of microcrystalline cellulose (MCC) for bioethanol production. The efficiency of MCC pretreatment followed with simultaneous saccharification and fermentation (SSF) was firstly evaluated according to the variations of the irradiation-derived compounds and structure of MCC, as well as yeast growth curve and bioethanol yield. Results showed that the appropriate irradiation dose (891 kGy used in our work) could eliminate the negative effect of toxic irradiation-derived compounds on SSF for ethanol bioconversion with the yield value of 67%. Analyses of SEM, FT-IR, reducing sugar and bioethanol yield showed that the efficiency of pretreatment on MCC was ILs ≈ irradiation pretreatment > AA-ILs pretreatment > 1% HCl pretreatment > 1% H2SO4 pretreatment.

Effect of revulsive cultivation on the yield and quality of newly formed sclerotia in medicinal Wolfiporia cocos.

Wolfiporia cocos is a well-known medicinal mushroom widely used in China, Japan and other Asiatic countries for its various therapeutic effects. 'Revulsive cultivation' is a newly developed method for promoting sclerotia growth in W. cocos field cultivation in China. In this report, we have systematically examined the effects of 'revulsive cultivation' on the yield and quality of newly formed sclerotia. The results showed that the genetic differences between the cultivated strain and the revulsive strain of T1 used in this study did not affect the formation process of new, large sclerotia in which the mycelia of the cultivated strain grew on pine logs directionally assembled on the revulsive strain. Additionally, 'revulsive cultivation', in which the cultivated strain and the revulsive strain used had the same or different genotypes, could remarkably increase the yield, lower the water content, and increase the water-soluble polysaccharide content of the newly formed sclerotia. Moreover, we observed that the changes in the values of the tested economic traits obtained from different genotype combinations through 'revulsive cultivation' were dissimilar. The correlations of these changes with the original sclerotium-forming ability of the cultivated strains and the genetic differences between the cultivated strain and the revulsive strain were not significant. These results will broaden our knowledge regarding the field cultivation of this medical fungus, stimulate new thinking on the study of sclerotium formation in some sclerotium-forming fungi, and promote further studies on the mechanism of sclerotium formation in W. cocos.

Association of the brain-derived neurotrophic factor gene G196A rs6265 polymorphisms and the cognitive function and clinical symptoms of schizophrenia.

UNLABELLED: This study aimed to explore the association between BDNF G196A gene rs6265 polymorphisms and the cognitive function and clinical symptoms of schizophrenia. METHODS: BDNF G196A rs6265 genotype and allele frequency were measured using Polymerase Chain Reaction (PCR) methods in 224 drug-free patients with schizophrenia and 220 controls. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and cognitive functioning was assessed using the Wisconsin Card Sorting Test (WCST) and the Trail Making Test (TMT). In the patient group, differences in severity of symptoms across the three genotypes (i.e., G/G, G/A and A/A) of G196A were assessed using one-way analysis of variance. RESULTS: G/A genotype had higher frequencies than GG or AA genotype in both patients and controls. There was no significant difference in G/G, G/A, A/A genotype frequency between patients and controls (P > 0.05). The allele G had higher frequencies than allele A in both patients and controls. There was no significant difference in G or A allele frequency between patients and controls (P > 0.05). There was significant difference in A/A genotype frequency between positive group patients and negative group patients. There was no significant difference in cognitive performance between patients with G/G, G/A and A/A genotype (all P > 0.05). CONCLUSION: BDNF G196A gene rs6265 polymorphism is not associated with the cognitive function but with the clinical symptoms of schizophrenia.

Associations between TCF4 gene polymorphism and cognitive functions in schizophrenia patients and healthy controls.

The SNP rs2958182 was reported to be significantly associated with schizophrenia (SCZ) in Han Chinese. This study examined this SNP's associations with cognitive functions in 580 SCZ patients and 498 controls. Cognitive functions were assessed using the Wechsler Adult Intelligence Scale-Revised (WAIS-RC), the Attention Network Task (ANT), the Stroop task, the dot pattern expectancy (DPX), task and the N-back working memory task. Results showed significant or marginally significant interaction effects between genotype and diagnosis status on IQ (P=0.011) and attention-related tasks (ie, the forward digit span of WAIS-RC, P=0.005; the ANT conflict effect; P=0.020, and its ratios over mean reaction time (RT), P=0.036; the Stroop conflict effect, P=0.032, and its ratios over mean RT, P=0.062; and the DPX task's error rate under the BX condition, P<0.001, and the error rate of BX minus the error rate of AY (BX-AY), P=0.002). There were no such interaction effects on the measures of working memory (all P-values >0.05). Further analysis of the significant genotype-by-diagnosis interactions showed that the risk (T) allele was associated with better performance on cognitive tasks in patients but with worse performance in controls. These results seem to indicate that the association between this SNP and selected cognitive functions may be of an inverted U-shaped pattern. Future research is needed to replicate these results and to explore the biochemical mechanisms behind this association.

Evidence of IQ-modulated association between ZNF804A gene polymorphism and cognitive function in schizophrenia patients.

ZNF804A gene polymorphism rs1344706 has been suggested as the most compelling case of a candidate gene for schizophrenia by a genome-wide association study and several replication studies. The current study of 570 schizophrenia patients and 448 controls again found significantly different genotype frequencies of rs1344706 between patients and controls. More important, we found that this association was modulated by IQ, with a stronger association among individuals with relatively high IQ, which replicated results of Walters et al, 2010. We further examined whether this IQ-modulated association also existed between the SNP and the intermediate phenotypes (working memory and executive functions) of schizophrenia. Data were available from an N-back task (366 patients and 414 controls) and the attention network task (361 patients and 416 controls). We found that the SNP and IQ had significant interaction effects on the intermediate phenotypes for patients, but not for controls. The disease risk allele was associated with poorer cognitive function in patients with high IQ, but better cognitive function in patients with low IQ. Together, these results indicated that IQ may modulate the role of rs1344706 in the etiology of both schizophrenia and its cognitive impairments, and pointed to the necessity of considering general cognitive function as indexed by IQ in the future studies of genetic bases of schizophrenia.

The effects of CACNA1C gene polymorphism on spatial working memory in both healthy controls and patients with schizophrenia or bipolar disorder.

CACNA1C gene polymorphism (rs1006737) is a susceptibility factor for both schizophrenia (SCZ) and bipolar disorder (BP). However, its role in working memory, a cognitive function that is impaired in both diseases, is not clear. Using three samples, including healthy controls, patients with SCZ, and patients currently in manic episodes of BP, this study tested the association between the SNP rs1006737 and spatial working memory as measured by an N-back task and a dot pattern expectancy (DPX) task. Among SCZ patients and healthy controls, the clinical risk allele was associated with impaired working memory, but the association was either in opposite direction or non-significant in patients with BP. These results indicated that rs1006737 may have differential effects on working memory in different disease populations and pointed to the necessity for more studies in different patient populations.