NS1-mediated enhancement of MVC transcription and replication promoted by KAT5/H4K12ac.

Histone modifications function in both cellular and viral gene expression. However, the roles of acetyltransferases and histone acetylation in parvoviral infection remain poorly understood. In the current study, we found the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), promoted the replication and transcription of parvovirus minute virus of canines (MVC). Notably, the expression of host acetyltransferases KAT5, GTF3C4, and KAT2A was increased in MVC infection, as well as H4 acetylation (H4K12ac). KAT5 is not only responsible for H4K12ac but also crucial for viral replication and transcription. The viral nonstructural protein NS1 interacted with KAT5 and enhanced its expression. Further study showed that Y44 in KAT5, which may be tyrosine-phosphorylated, is indispensable for NS1-mediated enhancement of KAT5 and efficient MVC replication. The data demonstrated that NS1 interacted with KAT5, which resulted in an enhanced H4K12ac level to promote viral replication and transcription, implying the epigenetic addition of H4K12ac in viral chromatin-like structure by KAT5 is vital for MVC replication.IMPORTANCEParvoviral genomes are chromatinized with host histones. Therefore, histone acetylation and related acetyltransferases are required for the virus to modify histones and open densely packed chromatin structures. This study illustrated that histone acetylation status is important for MVC replication and transcription and revealed a novel mechanism that the viral nonstructural protein NS1 hijacks the host acetyltransferase KAT5 to enhance histone acetylation of H4K12ac, which relies on a potential tyrosine phosphorylation site, Y44 in KAT5. Other parvoviruses share a similar genome organization and coding potential and may adapt a similar strategy for efficient viral replication and transcription.

VXX-401, a novel anti-PCSK9 vaccine, reduces LDL-C in cynomolgus monkeys.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of disease burden in the world and is highly correlated with chronic elevations of LDL-C. LDL-C-lowering drugs, such as statins or monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9), are known to reduce the risk of cardiovascular diseases; however, statins are associated with limited efficacy and poor adherence to treatment, whereas PCSK9 inhibitors are only prescribed to a "high-risk" patient population or those who have failed other therapies. Based on the proven efficacy and safety profile of existing monoclonal antibodies, we have developed a peptide-based vaccine against PCSK9, VXX-401, as an alternative option to treat hypercholesterolemia and prevent ASCVD. VXX-401 is designed to trigger a safe humoral immune response against PCSK9, resulting in the production of endogenous antibodies and a subsequent 30-40% reduction in blood LDL-C. In this article, VXX-401 demonstrates robust immunogenicity and sustained serum LDL-C-lowering effects in nonhuman primates. In addition, antibodies induced by VXX-401 bind to human PCSK9 with high affinity and block the inhibitory effect of PCSK9 on LDL-C uptake in a hepatic cell model. A repeat-dose toxicity study conducted in nonhuman primates under good laboratory practices toxicity indicated a suitable safety and tolerability profile, with injection site reactions being the main findings. As a promising safe and effective LDL-C-lowering therapy, VXX-401 may represent a broadly accessible and convenient option to treat hypercholesterolemia and prevent ASCVD.

Coronary artery wall contrast enhancement imaging impact on disease activity assessment in IgG4-RD: a direct marker of coronary involvement.

BACKGROUND: Coronary artery wall contrast enhancement (CE) has been applied to non-invasive visualization of changes to the coronary artery wall in systemic lupus erythematosus (SLE). This study investigated the feasibility of quantifying CE to detect coronary involvement in IgG4-related disease (IgG4-RD), as well as the influence on disease activity assessment. METHODS: A total of 93 subjects (31 IgG4-RD; 29 SLE; 33 controls) were recruited in the study. Coronary artery wall imaging was performed in a 3.0 T MRI scanner. Serological markers and IgG4-RD Responder Index (IgG4-RD-RI) scores were collected for correlation analysis. RESULTS: Coronary wall CE was observed in 29 (94 %) IgG4-RD patients and 22 (76 %) SLE patients. Contrast-to-noise ratio (CNR) and total CE area were significantly higher in patient groups compared to controls (CNR: 6.1 ± 2.7 [IgG4-RD] v. 4.2 ± 2.3 [SLE] v. 1.9 ± 1.5 [control], P < 0.001; Total CE area: 3.0 [3.0-6.6] v. 1.7 [1.5-2.6] v. 0.3 [0.3-0.9], P < 0.001). In the IgG4-RD group, CNR and total CE area were correlated with the RI (CNR: r = 0.55, P = 0.002; total CE area: r = 0.39, P = 0.031). RI´ scored considering coronary involvement by CE, differed significantly from RI scored without consideration of CE (RI v. RI´: 15 ± 6 v. 16 ± 6, P < 0.001). CONCLUSIONS: Visualization and quantification of CMR coronary CE by CNR and total CE area could be utilized to detect subclinical and clinical coronary wall involvement, which is prevalent in IgG4-RD. The potential inclusion of small and medium-sized vessel involvements in the assessment of disease activity in IgG4-RD is worthy of further investigation.

Aberrant brain intra- and internetwork functional connectivity in children with Prader-Willi syndrome.

PURPOSE: Prader-Willi syndrome (PWS) suffers from brain functional reorganization and developmental delays during childhood, but the underlying neurodevelopmental mechanism is unclear. This paper aims to investigate the intra- and internetwork functional connectivity (FC) changes, and their relationships with developmental delays in PWS children. METHODS: Resting-state functional magnetic resonance imaging datasets of PWS children and healthy controls (HCs) were acquired. Independent component analysis was used to acquire core resting-state networks (RSNs). The intra- and internetwork FC patterns were then investigated. RESULTS: In terms of intranetwork FC, children with PWS had lower FC in the dorsal attention network, the auditory network, the medial visual network (VN) and the sensorimotor network (SMN) than HCs (FWE-corrected, p < 0.05). In terms of internetwork FC, PWS children had decreased FC between the following pairs of regions: posterior default mode network (DMN) and anterior DMN; posterior DMN and SMN; SMN and posterior VN and salience network and medial VN (FDR-corrected, p < 0.05). Partial correlation analyses revealed that the intranetwork FC patterns were positively correlated with developmental quotients in PWS children, while the internetwork FC patterns were completely opposite (p < 0.05). Intranetwork FC patterns showed an area under the receiver operating characteristic curve of 0.947, with a sensitivity of 96.15% and a specificity of 81.25% for differentiating between PWS and HCs. CONCLUSION: Impaired intra- and internetwork FC patterns in PWS children are associated with developmental delays, which may result from neural pathway dysfunctions. Intranetwork FC reorganization patterns can discriminate PWS children from HCs. REGISTRATION NUMBER ON THE CHINESE CLINICAL TRAIL REGISTRY: ChiCTR2100046551.

Increased cortical lesion load contributed to pathological changes beyond focal lesion in cortical gray matter of multiple sclerosis: a diffusion kurtosis imaging analysis.

Biomarkers specific to cortical gray matter (cGM) pathological changes of multiple sclerosis (MS) are desperately needed to better understand the disease progression. The cGM damage occurs in cortical lesion (CL) and normal-appearing cGM (NAcGM) areas. While the association between CL load and cGM damage has been reported, little is known about how different CL types, i.e. intracortical lesion (ICL) and leukocortical lesion (LCL) would be associated with cGM damage. In our study, relapsing-remitting MS patients and healthy controls were divided into 4 groups according to CL load level. NAcGM diffusion kurtosis imaging (DKI)/diffusion tensor imaging (DTI) values and cGM volume (cGMV) were used to characterize the pathological changes in cGM. Univariate general linear model was used for group comparisons and stepwise regression analysis was used to assess the effects of ICL volume and LCL volume on NAcGM damage. We found peak values in DKI/DTI values, cGMV and neuropsychological scores in high CL load group. Kurtosis fractional anisotropy (KFA) was the most sensitive in characterizing NAcGM damage, and LCL volume related more to NAcGM damage. Our findings suggested KFA could become a surrogate biomarker to cGM damage, and LCL might be the main factor in whole brain NAcGM damage.

HPV16 E7 protein antagonizes TNF-α-induced apoptosis of cervical cancer cells via Daxx/JNK pathway.

Human papillomavirus (HPV) E7 protein as an important viral factor was involved in the progression of cervical cancer by mediating the cellular signaling pathways. Daxx (Death domain-associated protein) can interact with a variety of proteins to affect the viral infection process. However, the interaction and its related function between HPV16 E7 and Daxx have not been adequately investigated. Here, it was found that HPV16 E7 can interact with Daxx in HeLa or C33A cells by co-immunoprecipitation. HPV16 E7 protein treatment can up-regulate Daxx protein expression, while the interference in Daxx expression and the agonists for JNK can both reduce the antagonistic effects of HPV16 E7 on TNF-α-induced apoptosis, suggesting that Daxx/JNK pathway may be involved in the anti-apoptotic activity of HPV16 E7.

JAK3/STAT5b/PPARγ Pathway Mediates the Association between Di(2-ethylhexyl) Phthalate Exposure and Lipid Metabolic Disorder in Chinese Adolescent Students.

Our previous studies found that di (2-ethylhexyl) phthalate (DEHP) could disorder lipid metabolism in adolescents but the mechanisms underlying this association remained unclear. This study was undertaken to clarify the mediating effect of JAK3/STAT5/PPARγ on disorder lipid levels induced by DEHP in adolescents. We recruited 478 adolescent students (median age 18.1 years). The mRNA expression and DNA methylation levels of JAK3/STAT5/PPARγ were detected by real-time PCR and the MethylTarget, respectively. We used multiple linear regression to analyze the association between DEHP metabolites (MEHP, MEOHP, MEHHP, MECPP, MCMHP, and ΣDEHP) levels, mRNA expression, and DNA methylation levels. The mediating effect of JAK3/STAT5/PPARγ mRNA expression levels was examined by mediation analysis. We found that all DEHP metabolite levels were positively correlated with TC/HDL-C and LDL-C/HDL-C (P < 0.05). The MEOHP level was negatively associated with DNA methylation levels and positively associated with mRNA levels of PPARγ and STAT5b (P < 0.05). The MEHP level was negatively associated with the DNA methylation level and positively associated with the mRNA level of JAK3 (P < 0.05). Higher MEOHP was associated with a higher level of TC/HDL-C, the mediation analysis showed the mediation effect was 17.18% for the JAK3 level, 10.76% for the STAT5b level, and 11% for the PPARγ level. Higher MEHP was associated with a higher level of LDL-C/HDL-C, the mediation effect was 14.49% for the JAK3 level. In conclusion, DEHP metabolites decreased the DNA methylation levels, inducing the increase of the mRNA levels of JAK3/STAT5/PPARγ. In addition, the mRNA levels mediated the association between DEHP exposure and disorder lipid levels.

The Value of the Cardiac Magnetic Resonance Intravoxel Incoherent Motion Technique in Evaluating Microcirculatory Dysfunction in Hypertrophic Cardiomyopathy.

Objective: To evaluate the value of the cardiac magnetic resonance intravoxel incoherent motion (IVIM) technique in microcirculatory dysfunction in patients with hypertrophic cardiomyopathy (HCM). Methods: The medical records of 19 patients with HCM in our hospital from January 2020 to May 2021 were collected retrospectively, and 23 healthy people with a similar age and gender distribution to the patients with HCM were included as controls. All the included subjects underwent clinical assessment and cardiac magnetic resonance imaging. The original IVIM images were analysed, and the imaging parameters of each segment were measured. The HCM group was divided into non-hypertrophic myocardium and hypertrophic myocardium groups. The differences in imaging parameters between the normal and HCM groups were compared. A Spearman correlation analysis was used to explore the correlation between end-diastolic thickness (EDTH) and each IVIM parameter. Results: The D∗ and f values in the HCM group were lower than those in the normal group (p < 0.0001 and p = 0.004, respectively). The f, D, D∗, and EDTH values of the hypertrophic segment, non-hypertrophic segment, and normal groups were statistically significant (p < 0.05). The difference in D∗ values among the mild, moderate, severe, and very severe HCM groups was statistically significant (p < 0.05). There was a statistically significant difference in EDTH among the mild, moderate, severe, and very severe groups (p < 0.001). There were significant differences in the values of D, D∗, and f between the non-delayed enhancement group and the delayed enhancement group (p < 0.05). The EDTH values of 304 segments in the HCM group were negatively correlated with f (r = -0.219, p = 0.028) and D∗ values (r = -0.310, p < 0.001). Conclusion: The use of IVIM technology can achieve a non-invasive early quantitative assessment of microvascular disease in HCM without the injection of a contrast agent and provide a reference for the early diagnosis of and intervention in myocardial ischemia in patients with HCM.

N-modified carbon-coated NaTi2(PO4)3 as an anode with high capacity and long lifetime for sodium-ion batteries.

NASICON-type NaTi2(PO4)3 is recognized as a promising energy storage anode due to its high ionic conductivity and low cost. In this work, N-modified carbon-coated sodium titanium phosphate (NTPGN) composites were prepared by the sol-gel method by using sodium glutamate as a source of nitrogen and partial carbons. The addition of sodium glutamate forms a loose structure of nano-spherical flowers on the surface of sodium titanium phosphate, which shows a higher specific capacity, better rate performance, and excellent cycling performance compared to the carbon-coated titanium phosphate derived only from citric acid. The discharge capacities of NTPGN at 0.1 C, 5 C, 10 C, 20 C, and 30 C are 132.8, 132, 131.4, 105.9, and 98.2 mA h g-1, respectively. In particular, after 1000 cycles at 20 C, the discharge capacity is 102.6 mA h g-1 with a capacity retention rate of 96%. This work reveals that the combination of carbon coating and nitrogen doping using sodium glutamate improves the electrochemical performance of electrode materials.

Investigation of effect of the profile of screw flight on chocolate flow in 3D printing using an improved lattice Boltzmann method.

BACKGROUND: 3D printing provides a new way of molding chocolate with complex geometrical structures. The screw extruder can efficiently transport the liquid chocolate, which has been adopted to investigate the effect of the profile of the screw flight on the flow. First, the rheological behavior of the liquid chocolate is measured and the Cross equation is demonstrated as the proper rheological model. Then, based on the rheological behavior, an improved lattice Boltzmann method is creatively proposed, for which the effectiveness is validated by the classical Poiseuille flow. Third, the geometrical structure of the screw extruder is analyzed and transformed. The possible changes in the profiles of the screw flights are listed. Finally, the fluid analysis is conducted and the necessary streamlines figures, cloud charts and velocity distributions are obtained. RESULTS: The large dip angle in straight cases has an obvious effect on the velocity distribution and the common flow area. The position of the convex point is the additional important factor, whereas the concave profiles are the most moderate in the proposed cases. CONCLUSION: The changes in the profiles will affect the chocolate flow. The work is significant for extrusion theory in 3D printing. © 2022 Society of Chemical Industry.

miR-3154 promotes hepatocellular carcinoma progression via suppressing HNF4α.

MicroRNAs (miRNAs) play an important role in cancer proliferation, metastasis, drug resistance and apoptosis by targeting oncogenes or tumor suppressor genes. miR-3154 has been reported to be up-regulated in cervical cancer and leukemia, but its role in hepatocellular carcinoma (HCC) remains unclear. Here, we for the first time demonstrated that miR-3154 was elevated in HCC and liver cancer stem cells (CSCs). Up-regulated miR-3154 was associated with overall survival and disease-free survival of HCC patients. MiR-3154 knockdown inhibits HCC cells self-renewal, proliferation, metastasis, and tumorigenesis. Mechanistically, miR-3154 target directly to HNF4α. MiR-3154 knockdown upregulated HNF4α mRNA and protein expression. HNF4α interference abolish the differences of self-renewal, proliferation, metastasis, and tumorigenesis between miR-3154 knockdown cells and control hepatoma cells. Furthermore, miR-3154 expression was negatively correlated with HNF4α in HCC tissues. The combined HHC panels exhibited a better disease-free survival prognostic value for HCC patients than any of these components alone. More importantly, miR-3154 determines the responses of hepatoma cells to lenvatinib treatment. Analysis of patient cohort and patient-derived xenografts (PDXs) further suggest that miR-3154 might predict lenvatinib clinical benefit in HCC patients. In conclusion, we reveal the crucial role of miR-3514 in HCC progression and lenvatinib response, suggesting potential therapeutic targets for HCC.

Enhancing tryptophan production by balancing precursors in Escherichia coli.

Tryptophan, an essential aromatic amino acid, is widely used in animal feed, food additives, and pharmaceuticals. Although sustainable and environmentally friendly, microbial tryptophan production from renewable feedstocks is limited by low biosynthesis and transport rates. Here, an Escherichia coli strain capable of efficient tryptophan production was generated by improving and balancing the supply of precursors and by engineering membrane transporters. Tryptophan biosynthesis was increased by eliminating negative regulatory factors, blocking competing pathways, and preventing tryptophan degradation. Promoter engineering balanced the supply of the precursors erythrose-4-phosphate and phosphoenolpyruvate, as well as the availability of serine. Finally, the engineering of tryptophan transporters prevented feedback inhibition and growth toxicity. Fed-batch fermentation of the final strain (TRP12) in a 5 L bioreactor produced 52.1 g·L-1 of tryptophan, with a yield of 0.171 g·g-1 glucose and productivity of 1.45 g·L-1 ·h-1 . The metabolic engineering strategy described here paves the way for high-performance microbial cell factories aimed at the production of tryptophan as well as other valuable chemicals.

Thermal Activation of Coal Gangue with Low Al/Si Ratio as Supplementary Cementitious Materials.

To effectively utilize coal gangue (CG) with low Al/Si ratio, the thermal activation method was used. The activated CG, as supplementary cementitious materials (SCMs), was added into ordinary Portland cement (OPC) to study its physical properties. The XRD results show that CG undergoes a phase transition from kaolinite to metakaolinite during activation. The NMR tests reveal that the low polymerization state Q3 is continuously broadened, and the Al coordination gradually changes from Al VI to Al V and Al IV. The CG particles are scale-like and glassy with a loose structure. By mixing the activated CG (under 800 °C) with cement (mass ratio = 3:7), the water demand of normal consistency increases by 7.2% and the initial and final setting times extend by 67 min and 81 min, respectively. The rough surface and loose structure of activated CG are the main factors contributing to the higher water demand of normal consistency. The micro-aggregate effect of the activated CG reduces the contact rate between the cement particles and water, and the interparticles, thus slowing down the process of hydration reaction, and leading to longer setting times.

The utility of competency-oriented clinical laboratory teaching combined with case-based learning (CBL).

OBJECTIVES: This study aimed to evaluate the effectiveness and efficiency of competency-oriented clinical laboratory teaching combined with case-based learning (CBL) and improve the examination of students' competence of laboratory medicine. METHODS: A total of 107 medical laboratory medicine interns at the Affiliated Hospital of Xuzhou Medical University from June 2017 to July 2019 volunteered to participate in the study and were randomly assigned into a control group with training of the traditional teacher-centered method, and an experimental group under a CBL teaching program. Student basic theory tests and skill assessment were designed to evaluate what the students gained from their internship when they completed their studies at the Affiliated Hospital of Xuzhou Medical University. RESULTS: Compared to students in the control group taught with the teacher-centered method, those in the CBL teaching program had significantly higher theory test scores and skill assessment scores on average. Competencies with particularly significant improvement included identification and processing of instrument alarm information, analysis of test results, identification and solution of the problem, as well as identification and reporting of the critical value and clinical communication. CONCLUSIONS: The competency-oriented teaching method combined with CBL is an effective method for improving students' professional knowledge, increasing language expression, and enhancing interpersonal relationship and teamwork, which is worthy of being promoted in laboratory medicine teaching.

Effects of HPV16 E6 protein on Daxx-induced apoptosis in C33A cells.

AIMS: Daxx is a highly conserved nuclear protein with an important role in transcription, apoptosis and other cell processes. We investigated the role of HPV16 E6 in Daxx-induced apoptosis through their interactions in C33A cells. METHODS: The binding of HPV16 E6 and Daxx was confirmed in C33A cells using co-immunoprecipitation and indirect immunofluorescence assays. Quantitative PCR and western blotting were performed to determine the RNA and protein expressions of Daxx, respectively. Automatic cell count and MTT assays were performed to investigate the proliferation of C33A cells. The apoptosis rate of C33A cells was determined via flow cytometry using Annexin V-FITC/PI staining. The relative activity of caspase-8 was tested using ELISA. RESULTS: HPV16 E6 can bind with Daxx and cause its translocation in C33A cells. The transfected HPV16 E6 can cause a decrease in relative quantification for Daxx in Daxx-overexpressing cells. After Daxx transfection, cell proliferation was found to decrease sharply and cell apoptosis to increase sharply. However, when HPV16 E6 was co-transfected with Daxx, this decrease and increase both became gentle. Similarly, HPV16 E6 made the Daxx-induced increase in caspase-8 activity milder. CONCLUSIONS: HPV16 E6 is involved in inhibiting apoptosis through deregulation of Daxx-induced caspase-8 activities.

Age-related changes in neuroinflammation and prepulse inhibition in offspring of rats treated with Poly I:C in early gestation.

BACKGROUND: Maternal immune activation (MIA) during gestation can increase the later risk of schizophrenia in adult offspring. Neuroinflammation is believed to underlie this process. Postmortem brain studies have found changes in the neuroimmune systems of patients with schizophrenia. However, little is known about the dynamic changes in cerebral inflammation and behavior during the course of the disease. METHODS: Here, the prepulse inhibition (PPI) test was conducted in adolescent and adult Sprague-Dawley rats prenatally challenged with polyriboinosinic-polyribocytidylic acid (Poly I:C) on gestational day 9 to determine the behavioral trajectory triggered by early exposure to Poly I:C. Brain immune changes were determined in the prefrontal cortex (PFC) and hippocampus (HC) at both ages. The status of the microglia and astrocytes was determined with immunohistochemical staining. The levels of IL-6, IL-1ß, and TNF-α in both brain regions were evaluated with enzyme-linked immunosorbent assays. RESULTS: Disrupted PPI, the core phenotype of schizophrenia, only emerged in adulthood. Behavioral changes during puberty and adulthood were both accompanied by the activation of microglia (PFC and HC). Astrocytes were only activated at PN60. The levels of proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) in the offspring of the Poly I:C-exposed mothers differed with brain region and time, with more cytokines elevated during periadolescence than during adulthood. CONCLUSIONS: Our findings indicate that immune activation emerged before symptom manifestation in the offspring of MIA rats. We conclude that early prenatal Poly I:C challenge can lead to age-related behavioral and neuroinflammatory changes. These data provide new insight into the neuroinflammatory and neuropathological mechanisms underlying the development of schizophrenia. They also suggest that periadolescence could be more important than adulthood in the prevention and treatment of schizophrenia.

Urinary levels of phthalate metabolites and their association with lifestyle behaviors in Chinese adolescents and young adults.

BACKGROUND: Adolescence and young adulthood are critical periods of human growth and development. Phthalates are environmental endocrine disruptors, and their health hazards in adolescents and young adults cannot be ignored. This study was undertaken to assess phthalate exposure and determine the associations between lifestyle behaviors and phthalate metabolite levels in Chinese adolescents and young adults. METHODS: Four hundred and seventy-eight adolescents and young adults aged 16-20 years were included in this study. The levels of mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-carboxmethyl)-hexyl phthalate (MCMHP) in the subjects' urine were measured by high-performance liquid chromatography-tandem mass spectrometry. The estimated daily intake (EDI) and hazard index (HI) of phthalates were calculated based on urinary metabolite levels. Relevant information on the subjects was collected via questionnaires. The associations between phthalate metabolite levels and lifestyle behaviors were examined using the independent-sample t-test, Mann-Whitney test and multiple linear regression. RESULTS: In this study, the detection rates of all seven metabolites were >98%. The highest median metabolite concentration was MBP, which was 43.00 µg/L (33.11 µg/g creatinine). The highest median EDI was for di-(2-ethylhexyl) phthalate (DEHP), which was 2.40 µg/kg-bw/day (volume-based) and 1.51 µg/kg-bw/day (creatinine-based). 2.7% (volume-based) and 1.0% (creatinine-based) of the subjects showed excessive HITDI (HI of the tolerable daily intake) values, which indicated the cumulative risk of anti-androgenic effects. Furthermore, factors significantly associated with phthalate metabolite levels included the use of plastic food packages (DEHP metabolites), physical exercise (MEOHP), the frequency of fast food consumption (MBP), and the frequency of skin care cosmetics and color cosmetics use (MEP). CONCLUSION: Our results suggest that Chinese adolescents and young adults are widely exposed to phthalates and their metabolite levels are influenced by lifestyle behaviors.

Association between cerebral dopamine neurotrophic factor (CDNF) 2 polymorphisms and schizophrenia susceptibility and symptoms in the Han Chinese population.

BACKGROUND: Schizophrenia (SZ) is a complex polygenic psychiatric disorder caused in part by abnormal dopamine levels. Cerebral dopamine neurotrophic factor (CDNF) 2 is known to protect and repair the dopaminergic system. Dopamine dysfunction is one of the pathogenesis of SZ. However, the relationship between CDNF2 and SZ has not been previously investigated. We speculated that CDNF2 may be a susceptibility factor for SZ. METHODS: To address this issue, we carried out a study to investigate the association between CDNF2 and SZ in the total sample 1371 (670 SZ patients and 701 healthy controls) Han Chinese population. Stage 1 included 528 SZ patients and 528 healthy controls; and stage 2 included 142 SZ patients and 173 healthy controls. The allele and genotype frequencies of five single nucleotide polymorphisms (rs2577074, rs2577075, rs2249810, rs6506891, and rs2118343) of CDNF2 were compared between patients and controls. RESULTS: We found a significant association in allele and genotype frequencies between the two groups at rs2249810 (χ2 = 4.38 and 6.45, respectively; P = 0.03 and 0.04, respectively). An association was also observed in males at rs2249810 (χ2 = 8.76; P = 0.03). Haplotype TGATC differed between SZ and controls in stage 2 samples (χ2 = 6.38; P = 0.01), and rs2118343 genotypes were associated with negative factor scores (F = 4.396; P = 0.01). CONCLUSIONS: These results suggest that rs2249810 and haplotype TGATC of CDNF2 are an SZ susceptibility locus and factor, respectively, and that rs2118343 genotypes are associated with negative symptoms of SZ in the Han Chinese population.

Bioactive Azaphilone Derivatives from the Fungus Talaromyces aculeatus.

Six new azaphilone derivatives, talaraculones A-F (1-6), together with five known analogues (7-11), were obtained from the saline soil-derived fungus Talaromyces aculeatus. The absolute configurations of 1 and 6 were assigned by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. Compounds 1 and 5 represent the first reported azaphilone derivatives with a C4 aliphatic side chain and a methylal group at C-3, respectively. Talaraculones A and B (1 and 2) exhibited stronger inhibitory activity against α-glucosidase than the positive control acarbose (IC50 = 101.5 µM), with IC50 values of 78.6 and 22.9 µM, respectively.

Wnt/ß-Catenin Signaling Exacerbates Keloid Cell Proliferation by Regulating Telomerase.

OBJECTIVES: Our goal was to investigate the relationship between keloid and telomerase as well as clarifying the influence of Wnt/ß-catenin signaling on keloid cell proliferation. METHODS: Tissues from 18 keloid patients were collected for further study. Keloid progenitor cells (KPC) and skin progenitor cells (SKP) were both included in this study. Lenti-virus transfection was used to divide cells into different groups in which cells were treated with different substances: negative control (NC) group, wnt10a siRNA group, ß-catenin siRNA group and TERT siRNA group. KPC cells were injected into 20 male BALB/c nude mice in order to build tumor models. Several experiments including immunohistochemistry, western blot and RT-PCR were conducted in order to detect the corresponding protein expressions and relative mRNA levels. MTT assay and flow cytometry were also conducted for assessing cell proliferation and apoptosis status. RESULTS: ß-catenin and telomerase expression levels in keloid tissues were elevated compared to normal tissues (all P < 0.05). KPC cells in keloid exhibited more dynamic telomerase activity than SKP cells (P < 0.05). Luciferase activity assay confirmed that ß-catenin could directly interact with telomerase. After wnt10a/ß-catenin signaling pathway was inhibited, the proliferation of KPC cells was significantly suppressed and the apoptosis rate was remarkably increased (all P < 0.05). Results from tumor models also validated that wnt10a/ß-catenin signaling pathway influenced the activity and length of telomerase. CONCLUSIONS: Wnt/ß-catenin signaling pathway is able to exacerbate keloid cell proliferation and inhibit the apoptosis of keloid cells through its interaction with telomerase.