The RNA polymerase of cytoplasmically replicating Zika virus binds with chromatin DNA in nuclei and regulates host gene transcription.

Zika virus (ZIKV) targets the neural progenitor cells (NPCs) in brain during intrauterine infections and consequently causes severe neurological disorders, such as microcephaly in neonates. Although replicating in the cytoplasm, ZIKV dysregulates the expression of thousands of host genes, yet the detailed mechanism remains elusive. Herein, we report that ZIKV encodes a unique DNA-binding protein to regulate host gene transcription in the nucleus. We found that ZIKV NS5, the viral RNA polymerase, associates tightly with host chromatin DNA through its methyltransferase domain and this interaction could be specifically blocked by GTP. Further study showed that expression of ZIKV NS5 in human NPCs markedly suppressed the transcription of its target genes, especially the genes involved in neurogenesis. Mechanistically, ZIKV NS5 binds onto the gene body of its target genes and then blocks their transcriptional elongation. The utero electroporation in pregnant mice showed that NS5 expression significantly disrupts the neurogenesis by reducing the number of Sox2- and Tbr2-positive cells in the fetal cortex. Together, our findings demonstrate a molecular clue linking to the abnormal neurodevelopment caused by ZIKV infection and also provide intriguing insights into the interaction between the host cell and the pathogenic RNA virus, where the cytoplasmic RNA virus encodes a DNA-binding protein to control the transcription of host cell in the nuclei.

Microcephaly Gene Mcph1 Deficiency Induces p19ARF-Dependent Cell Cycle Arrest and Senescence.

MCPH1 has been identified as the causal gene for primary microcephaly type 1, a neurodevelopmental disorder characterized by reduced brain size and delayed growth. As a multifunction protein, MCPH1 has been reported to repress the expression of TERT and interact with transcriptional regulator E2F1. However, it remains unclear whether MCPH1 regulates brain development through its transcriptional regulation function. This study showed that the knockout of Mcph1 in mice leads to delayed growth as early as the embryo stage E11.5. Transcriptome analysis (RNA-seq) revealed that the deletion of Mcph1 resulted in changes in the expression levels of a limited number of genes. Although the expression of some of E2F1 targets, such as Satb2 and Cdkn1c, was affected, the differentially expressed genes (DEGs) were not significantly enriched as E2F1 target genes. Further investigations showed that primary and immortalized Mcph1 knockout mouse embryonic fibroblasts (MEFs) exhibited cell cycle arrest and cellular senescence phenotype. Interestingly, the upregulation of p19ARF was detected in Mcph1 knockout MEFs, and silencing p19Arf restored the cell cycle and growth arrest to wild-type levels. Our findings suggested it is unlikely that MCPH1 regulates neurodevelopment through E2F1-mediated transcriptional regulation, and p19ARF-dependent cell cycle arrest and cellular senescence may contribute to the developmental abnormalities observed in primary microcephaly.

Factors influencing traumatic brain injuries in maxillofacial fractures: A 12-year retrospective analysis of 2841 patients.

BACKGROUND/AIM: Results of studies investigating the association between traumatic brain injury (TBI) and maxillofacial fractures (MFs) have varied considerably. The present study aimed to evaluate the correlation between TBIs and MFs, as well as the impact of age, sex, trauma mechanism, and season on TBIs. MATERIALS AND METHODS: This 12-year retrospective study of 2841 patients used univariate and multivariate logistic regression to assess the association between MFs and other factors impacting TBIs. RESULTS: Among 2841 patients, 1978 TBIs occurred in 829 (29.2%), with intracranial injuries (n = 828) is the most common. Of 829 patients with TBIs, 688 were male and 141 were female, corresponding to a male-to-female ratio of 4.9:1.0. The most common age group was 40-49 years (24.6%). Vehicles (including motor vehicles and electric vehicles) accidents were the primary causes of injuries. Multivariate regression analyses revealed an increased risk for TBIs among males (odds ratio [OR] 0.632, p < 0.001). Patients >40 years of age were at higher risk for TBIs, especially those ≥70 years (OR 3.966, p = 0.001). Vehicle accidents were a high-risk factor for TBIs (OR 6.894, p < 0.001), and winter was the most prevalent season for such injuries (OR 1.559, p = 0.002). Risk for TBI increased by 136.4% in combined midfacial and mandibular fractures (p = 0.016) and by 101.6% in multiple midfacial fractures (p = 0.045). TBIs were less common in single mandibular fractures, notably in single-angle fractures, with a risk of only 0.204-fold. CONCLUSION: TBIs in MFs were significantly correlated with sex, age, aetiology, season and fracture location. Maxillofacial surgeons and emergency physicians must be aware of the possible association between TBIs and MFs to assess and manage this complicated relationship in a timely manner.

Biology and Roles in Diseases of Selenoprotein I Characterized by Ethanolamine Phosphotransferase Activity and Antioxidant Potential.

Selenoprotein I (SELENOI) has been demonstrated to be an ethanolamine phosphotransferase (EPT) characterized by a nonselenoenzymatic domain and to be involved in the main synthetic branch of phosphatidylethanolamine (PE) in the endoplasmic reticulum. Therefore, defects of SELENOI may affect the health status through the multiple functions of PE. On the other hand, selenium (Se) is covalently incorporated into SELENOI as selenocysteine (Sec) in its peptide, which forms a Sec-centered domain as in the other members of the selenoprotein family. Unlike other selenoproteins, Sec-containing SELENOI was formed at a later stage of animal evolution, and the high conservation of the structural domain for PE synthesis across a wide range of species suggests the importance of EPT activity in supporting the survival and evolution of organisms. A variety of factors, such as species characteristics (age and sex), diet and nutrition (dietary Se and fat intakes), SELENOI-specific properties (tissue distribution and rank in the selenoproteome), etc., synergistically regulate the expression of SELENOI in a tentatively unclear interaction. The N- and C-terminal domains confer 2 distinct biochemical functions to SELENOI, namely PE regulation and antioxidant potential, which may allow it to be involved in numerous physiological processes, including neurological diseases (especially hereditary spastic paraplegia), T cell activation, tumorigenesis, and adipocyte differentiation. In this review, we summarize advances in the biology and roles of SELENOI, shedding light on the precise regulation of SELENOI expression and PE homeostasis by dietary Se intake and pharmaceutical or transgenic approaches to modulate the corresponding pathological status.

Serum amyloid A and risks of all-cause and cardiovascular mortality in chronic kidney disease: a systematic review and dose-response meta-analysis.

BACKGROUNDS: The available literature on the correlation between serum amyloid A (SAA) and prognosis of chronic kidney disease (CKD) are limited, and the findings from existing studies are inconclusive. This meta-analysis aimed to evaluate the available evidence regarding the link between SAA and risks of all-cause and cardiovascular mortality in CKD patients. Additionally, we aimed to investigate the potential dose-response relationships, provided that adequate data is accessible. METHODS: Pubmed and Embase were searched for related literature (last update: 12 July 2023). The pooled effect estimates were calculated using random- or fixed-effects models depending on heterogeneity among studies. RESULTS: This meta-analysis incorporated 8 studies encompassing 2331 CKD patients. The findings revealed an 85% increase in all-cause mortality risk [hazard risk (HR) 1.85, 95% confidence interval (CI) 1.29-2.65] and a 39% increase in cardiovascular mortality risk (HR 1.07, 95% CI 1.07-1.80) when comparing the highest tertile of baseline SAA levels to the lowest tertile. Furthermore, a positive linear relationship between SAA and all-cause mortality risk was observed (Pnon-linearity = 0.959), with a 17.7% increase in risk for each 10 mg/L SAA increase (HR 1.177, 95% CI 1.055-1.313). Similarly, a linear relationship between SAA and cardiovascular mortality risk was identified (Pnon-linearity = 0.477) with a 19.3% increase in risk for each 10 mg/L SAA increase (HR 1.193, 95% CI 1.025-1.388). CONCLUSIONS: This meta-analysis provided evidence that SAA levels are positively and linearly associated with risks of all-cause and cardiovascular mortality among CKD patients.

Epidemiology of maxillofacial fractures in northwest China: an 11-year retrospective study of 2240 patients.

BACKGROUND: The aim of this study was to determine the epidemiological pattern of maxillofacial fractures in northwestern China by retrospectively analysing the demographics, aetiologies, concomitant injuries, fracture sites, and management. METHODS: A 10-year retrospective analysis of 2240 patients with maxillofacial fractures admitted to the General Hospital of Ningxia Medical University was conducted. The extracted data included sex, age, aetiology, fracture site, concomitant injuries, time of treatment, therapeutic approaches and complications. Statistical analyses were performed, including descriptive analysis and the chi-square test. Logistic regression was used to determine the impact factors of maxillofacial fractures and concomitant injuries. P values < 0.05 were considered statistically significant. RESULTS: The age of the included patients ranged from 1 to 85 years, and the mean age was 35.88 ± 15.69 years. The male-to-female ratio was 3.9:1. The most frequent aetiology of maxillofacial fractures was road traffic accidents (RTAs) (56.3%), and the most common fracture sites were the anterior wall of the maxillary sinus, arcus zygomaticus and mandibular body. A total of 1147 patients (51.2%) were affected by concomitant injuries, with craniocerebral injury being the most common. Logistic regression analyses revealed increased risks of mid-facial fractures in elderly individuals (odds ratio (OR) = 1.029, P < 0.001) and females (OR = 0.719, P = 0.005). Younger patients had a higher risk of mandibular fractures (OR = 0.973, P < 0.001). RTAs increased the risk for mid-facial fractures and high falls increased the risk for mandibular fractures. CONCLUSIONS: The maxillofacial fracture pattern is correlated with sex, age and aetiology. Patients were mainly young and middle-aged males, and the main cause of injury was RTAs, mostly causing compound fractures. Medical staff must be systematically educated to comprehensively examine patients with injuries resulting from RTAs. The management of patients with fractures requires thorough consideration of the patient's age, aetiology, fracture site, and concomitant injuries.

Discovery of a small-molecule inhibitor targeting the ovarian tumor domain of a novel Tamdy orthonairoviruse associated with human febrile illness.

Tick-borne orthonairoviruses have been characterized as a global health threat to humans and animals. Tacheng Tick virus 1 (TcTV-1) from this family was provided as evidence that is associated with the febrile illness syndrome. Here, we first identify and demonstrate that the ovarian tumor (OTU) domain of TcTV-1 has remarkable deubiquitinating activity both in vitro and in vivo. By solving the crystal structure of TcTV-1 OTU (tcOTU) domain and comparing it to that of human deubiquitinating enzymes, we found that overall structures of tcOTU and human OTU family are similar, but the residues involved in the catalytic pocket vary widely. Based on the tcOTU domain we screened 5090 bioactive compounds and found mecobalamin had a good effect on suppressing the deubiquitinating activity. The structural model of tcOTU and mecobalamin suggests that mecobalamin occupies the site of the substrate Ub, by blocking the substrate binding to the enzyme. Thus, our results showed OTU domain of TcTV-1 has a robust deubiquitinating activity and mecobalamin or its derivatives might be promising candidates for the treatment or prevention of disease caused by the TcTV-1 virus.

A pilot study of differential gene expressions in patients with cough variant asthma and classic bronchial asthma.

BACKGROUND: Despite extensive exploration of asthma, the mechanism of asthma has not been fully elucidated. Cough variant asthma (CVA) is considered as precursor to classical asthma (CA). Comparative study between CA and CVA may be helpful in further understanding the pathogenesis of asthma. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from CVA, CA and healthy adults. Each group consisted of five cases. Total RNA was extracted from the PBMCs. Agilent 4 × 44 K human genome oligo microarray was used to detect whole genome expression. Allogeneic clustering, Gene Ontology and KEGG analysis were performed to investigate differentially expressed genes (DEGs). Then, ten candidate genes were screened and verified by real-time PCR. RESULTS: Gene expressions were significantly different among the three groups, with 202 DEGs between the CA and the CVA groups. The Gene Ontology analysis suggested that the DEGs were significantly enriched in 'histone H4-K20 demethylation' and 'antigen processing and presentation of endogenous antigens'. HDC, EGR1, DEFA4, LTF, G0S2, IL4, TFF3, CTSG, FCER1A and CAMP were selected as candidate genes. However, the results of real-time PCR showed that the expression levels of FCER1A, IL4 and HDC in the cough variant asthma group were significantly different from those in the other two groups (p < 0.05). CONCLUSIONS: The pathogenesis of CVA and CA may be related to genes such as FCER1A, HDC and IL4. Further studies incorporating a larger sample size should be conducted to find more candidate genes and mechanisms.

NBS1 interacts with Notch signaling in neuronal homeostasis.

NBS1 is a critical component of the MRN (MRE11/RAD50/NBS1) complex, which regulates ATM- and ATR-mediated DNA damage response (DDR) pathways. Mutations in NBS1 cause the human genomic instability syndrome Nijmegen Breakage Syndrome (NBS), of which neuronal deficits, including microcephaly and intellectual disability, are classical hallmarks. Given its function in the DDR to ensure proper proliferation and prevent death of replicating cells, NBS1 is essential for life. Here we show that, unexpectedly, Nbs1 deletion is dispensable for postmitotic neurons, but compromises their arborization and migration due to dysregulated Notch signaling. We find that Nbs1 interacts with NICD-RBPJ, the effector of Notch signaling, and inhibits Notch activity. Genetic ablation or pharmaceutical inhibition of Notch signaling rescues the maturation and migration defects of Nbs1-deficient neurons in vitro and in vivo. Upregulation of Notch by Nbs1 deletion is independent of the key DDR downstream effector p53 and inactivation of each MRN component produces a different pattern of Notch activity and distinct neuronal defects. These data indicate that neuronal defects and aberrant Notch activity in Nbs1-deficient cells are unlikely to be a direct consequence of loss of MRN-mediated DDR function. This study discloses a novel function of NBS1 in crosstalk with the Notch pathway in neuron development.

Combination RSL3 Treatment Sensitizes Ferroptosis- and EGFR-Inhibition-Resistant HNSCCs to Cetuximab.

Head and neck squamous cell carcinomas (HNSCCs) are a type of cancer originating in the mucosal epithelium of the mouth, pharynx, and larynx, the sixth most common cancer in the world. However, there is no effective treatment for HNSCCs. More than 90% of HNSCCs overexpress epidermal growth factor receptors (EGFRs). Although small molecule inhibitors and monoclonal antibodies have been developed to target EGFRs, few EGFR-targeted therapeutics are approved for clinical use. Ferroptosis is a new kind of programmed death induced by the iron catalyzed excessive peroxidation of polyunsaturated fatty acids. A growing body of evidence suggests that ferroptosis plays a pivotal role in inhibiting the tumor process. However, whether and how ferroptosis-inducers (FINs) play roles in hindering HNSCCs are unclear. In this study, we analyzed the sensitivity of different HNSCCs to ferroptosis-inducers. We found that only tongue squamous cell carcinoma cells and laryngeal squamous cell carcinoma cells, but not nasopharyngeal carcinoma cells, actively respond to ferroptosis-inducers. The different sensitivities of HNSCC cells to ferroptosis induction may be attributed to the expression of KRAS and ferritin heavy chain (FTH1) since a high level of FTH1 is associated with the poor prognostic survival of HNSCCs, but knocked down FTH1 can promote HNSCC cell death. Excitingly, the ferroptosis-inducer RSL3 plays a synthetic role with EGFR monoclonal antibody Cetuximab to inhibit the survival of nasopharyngeal carcinoma cells (CNE-2), which are insensitive to both ferroptosis induction and EGFR inhibition due to a high level of FTH1 and a low level of EGFR, respectively. Our findings prove that FTH1 plays a vital role in ferroptosis resistance in HNSCCs and also provide clues to target HNSCCs resistant to ferroptosis induction and/or EGFR inhibition.

Association between platelet indices and non-alcoholic fatty liver disease: a systematic review and meta-analysis.

BACKGROUND: Platelet indices have the potential for the evaluation of the activity of non-alcoholic fatty liver disease (NAFLD), but their associations are under hard debate. This meta-analysis aims to assess whether platelet count (PC), mean platelet volume (MPV) and platelet distribution width (PDW) are associated with NAFLD and its progression. METHODS: A literature search was conducted using electronic databases to find publications up to July 2022, where the relationship between PC, MPV, PDW and NAFLD was evaluated. Random-effects models were applied to pool effect estimates that were presented as standardized mean differences (SMD) with 95% confidence interval (CI). RESULTS: Nineteen studies involving 3592 NAFLD patients and 1194 healthy individuals were included. The pooled results showed that NAFLD patients had a lower PC (SMD=-0.66, 95% CI =-1.22 to -0.09, P=0.023) but a higher MPV (SMD=0.89, 95% CI=0.26-1.51, P=0.005) and PDW (SMD=0.55, 95% CI=0.11-0.99, P=0.014) compared to healthy controls. Patients with non-alcoholic steatohepatitis (NASH) exhibited a lower PC (SMD=-0.86, 95% CI=-1.20 to -0.52, P<0.001) and a higher MPV (SMD=0.71, 95% CI=0.40-1.02, P<0.001) than non-NASH individuals. A meta-regression analysis demonstrated that MPV was significantly positively correlated with aspartate aminotransferase (P=0.008), the total cholesterol (P=0.003), triglyceride (P=0.006) and low-density lipoprotein cholesterol (P=0.007), but was significantly negatively correlated with high-density lipoprotein cholesterol (P=0.010). CONCLUSION: This meta-analysis revealed that NAFLD patients presented a reduced PC but an increased MPV and PDW, and the changes might be associated with NAFLD severity. A higher MPV is associated with lipid metabolic disorders in NAFLD.

Aminoacyl-tRNA synthetases in Charcot-Marie-Tooth disease: A gain or a loss?

Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurodegenerative disorders with an increasing number of CMT-associated variants identified as causative factors, however, there has been no effective therapy for CMT to date. Aminoacyl-tRNA synthetases (aaRS) are essential enzymes in translation by charging amino acids onto their cognate tRNAs during protein synthesis. Dominant monoallelic variants of aaRSs have been largely implicated in CMT. Some aaRSs variants affect enzymatic activity, demonstrating a loss-of-function property. In contrast, loss of aminoacylation activity is neither necessary nor sufficient for some aaRSs variants to cause CMT. Instead, accumulating evidence from CMT patient samples, animal genetic studies or protein conformational analysis has pinpointed toxic gain-of-function of aaRSs variants in CMT, suggesting complicated mechanisms underlying the pathogenesis of CMT. In this review, we summarize the latest advances in studies on CMT-linked aaRSs, with a particular focus on their functions. The current challenges, future direction and the promising candidates for potential treatment of CMT are also discussed.

The E3 ubiquitin ligase APC/CCdh1 degrades MCPH1 after MCPH1-ßTrCP2-Cdc25A-mediated mitotic entry to ensure neurogenesis.

Mutations of microcephalin (MCPH1) can cause the neurodevelopmental disorder primary microcephaly type 1. We previously showed that MCPH1 deletion in neural stem cells results in early mitotic entry that distracts cell division mode, leading to exhaustion of the progenitor pool. Here, we show that MCPH1 interacts with and promotes the E3 ligase ßTrCP2 to degrade Cdc25A independent of DNA damage. Overexpression of ßTrCP2 or the knockdown of Cdc25A remedies the high mitotic index and rescues the premature differentiation of Mcph1-deficient neuroprogenitors in vivo MCPH1 itself is degraded by APC/CCdh1, but not APC/CCdc20, in late mitosis and G1 phase. Forced MCPH1 expression causes cell death, underlining the importance of MCPH1 turnover after mitosis. Ectopic expression of Cdh1 leads to premature differentiation of neuroprogenitors, mimicking differentiation defects of Mcph1-knockout neuroprogenitors. The homeostasis of MCPH1 in association with the ubiquitin-proteasome system ensures mitotic entry independent of cell cycle checkpoint. This study provides a mechanistic understanding of how MCPH1 controls neural stem cell fate and brain development.

A Shortage of FTH Induces ROS and Sensitizes RAS-Proficient Neuroblastoma N2A Cells to Ferroptosis.

Ferroptosis, an iron-dependent form of programmed cell death, has excellent potential as an anti-cancer therapeutic strategy in different types of tumors, especially in RAS-mutated ones. However, the function of ferroptosis for inhibiting neuroblastoma, a common child malignant tumor with minimal treatment, is unclear. This study investigated the anti-cancer function of ferroptosis inducer Erastin or RSL3 in neuroblastoma N2A cells. Our results show that Erastin or RSL3 induces ROS level and cell death and, therefore, reduces the viability of RAS-proficient N2A cells. Importantly, inhibitors to ferroptosis, but not apoptosis, ameliorate the high ROS level and viability defect in Erastin- or RSL3-treated cells. In addition, our data also show that N2A cells are much more sensitive to ferroptosis inducers than primary mouse cortical neural stem cells (NSCs) or neurons. Moreover, a higher level of ROS and PARylation is evidenced in N2A, but not NSCs. Mechanically, ferritin heavy chain 1 (Fth), the ferroxidase function to oxidate redox-active Fe2+ to redox-inactive Fe3+, is likely responsible for the hypersensitivity of N2A to ferroptosis induction since its expression is lower in N2A compared to NSCs; ectopic expression of Fth reduces ROS levels and cell death, and induces expression of GPX4 and cell viability in N2A cells. Most importantly, neuroblastoma cell lines express a significantly low level of Fth than almost all other types of cancer cell lines. All these data suggest that Erastin or RSL3 induce ferroptosis cell death in neuroblastoma N2A cells, but not normal neural cells, regardless of RAS mutations, due to inadequate FTH. This study, therefore, provides new evidence that ferroptosis could be a promising therapeutic target for neuroblastoma.

Platelet indices in patients with chronic inflammatory arthritis: a systematic review and meta-analysis.

Correlation between platelet indices and chronic inflammatory arthritis (CIA) remains a moot point today. This meta-analysis aimed to evaluate whether platelet (PLT) count, mean platelet volume (MPV) and platelet distribution width (PDW) associated with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). A systematic literature search was performed in PubMed, EMBASE, and Web of Science up to August 2019. Pooled standardized mean differences (SMD) and 95% confidence interval (CI) were calculated using a random-effect model. As a result, 34 studies were included, encompassing 17 on RA, 12 on AS, 3 on PsA and 2 on both RA and AS. In these studies, PLT count was significantly higher in RA (SMD = 0.55, 95% CI = 0.36-0.73, P < .001), AS (SMD = 0.53, 95% CI = 0.36-0.70, P < .001) and PsA patients (SMD = 1.29, 95% CI = 0.82-1.77, P < .001) than that in healthy subjects, while MPV and PDW presented nonsignificant differences in these intergroup comparisons (P > .05), and similar results were observed in subgroup analyses. The meta-regression analysis demonstrated that there were strong positive correlations between erythrocyte sedimentation rate and PLT count, and weak correlation trend between the disease activity score and PLT count in both RA and AS subjects without statistically significant difference. The sensitivity analysis indicated that these results were not unduly influenced by any single study. In conclusion, this meta-analysis demonstrated that PLT count was elevated in CIA patients and could be suitable for evaluating the disease activity, whereas MPV and PDW were independent of CIA.

Identification and functional characterization of a hemizygous novel intronic variant in OCRL gene causes Lowe syndrome.

BACKGROUND: Lowe syndrome is an X-linked multisystem disorder affecting eyes, nervous system, and kidney. The main causes are mutations in the OCRL gene that encodes a member of the inositol polyphosphate-5-phosphatase protein family. In this study, we aimed to gain new insights into the consequences of a novel OCRL intronic variant on pre-mRNA splicing as a main cause of Lowe syndrome in a boy. METHODS: After clinical diagnosis of the patient with Lowe syndrome, genetic testing was used to detect the presence of the OCRL variants. In silico analysis, human splicing finder and PyMol were used to predict this variant effect. Then, we analyzed the variant transcript by using a minigene construct in addition to in silico analysis. RESULTS: A hemizygous novel splicing variant in the intron 10 splice donor site of OCRL (c.939 + 3A > C) was identified in a boy with Lowe syndrome. We detected that the splice junction variant leads to aberrant OCRL mRNA splicing which results in the formation of an alternative transcript in which 29 nucleotides of exon 10 were skipped. The findings obtained from the exon-trapping assay were identical to those of in silico analysis. Hence, the truncated OCRL protein may lacked the last 597 native amino acids. CONCLUSIONS: The minigene assays detected the same transcript abnormality to in silico assay and were reliable in revealing the pathogenicity of the intronic variant we have used previously. Overall, this study provides new insights about Lowe syndrome and further reveals the molecular pathogenicity mechanism of the intronic variant disease.

Fetuin-a to adiponectin ratio is a sensitive indicator for evaluating metabolic syndrome in the elderly.

BACKGROUND: Fetuin-A and adiponectin present significant associations, supported by recent evidence, with metabolic syndrome (MS) featuring hyperglycemia, central obesity and insulin resistance as the main components, but their biological functions are opposite. The aim of this study was to verify whether fetuin-A/adiponectin ratio (F/A ratio) is a more sensitive indicator for evaluation of MS than either fetuin-A or adiponectin. METHODS: In this cross-sectional study, 465 elderly subjects were selected from the physical examination database. Serum levels of fetuin-A and adiponectin were measured using an enzyme-linked immunosorbent assay (ELISA) method. Spearman's rank correlation coefficient, linear regression and logistic regression analysis were adopted to estimate the correlations of fetuin-A, adiponectin and F/A ratio with MS and its components, and receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive values of the aforesaid indices. RESULTS: Compared with fetuin-A or adiponectin, F/A ratio was significantly associated with all the components of MS, and this correlation was significant even after adjusting potential confounding factors (P < 0.05). Logistic regression analysis indicated that F/A ratio presented a stronger correlation with incident MS (adjusted OR: 1.466; 95% CI: 1.189-1.808) than fetuin-A (adjusted OR: 1.100; 95% CI: 1.020-1.186) and adiponectin (adjusted OR: 0.760; 95% CI: 0.664-0.871) alone. ROC analysis revealed that F/A ratio achieved a larger area under curve (AUC) than fetuin-A and adiponectin, with their AUC values of 0.755, 0.709 and 0.708, respectively. CONCLUSION: F/A ratio is a more sensitive index for evaluating MS than either fetuin-A or adiponectin in the elderly.

Morphology Modulation of Direct Inkjet Printing by Incorporating Polymers and Surfactants into a Sol-Gel Ink System.

Many methods have been reported to prevent the nonuniformity of inkjet printing structures. Most of them depend on the balance of the capillary flow in the printing pattern during the evaporation of the solvent. However, as the relation of evaporation and capillary flow can obviously vary among different ink systems, it is difficult for a method to fit most of the situations. Therefore, it would be a promising way to eliminate any capillary flow before solvent evaporation so that morphology of the printing structure will not be affected by the evaporation behavior of the ink system. In this paper, a novel method of direct inkjet printing of a uniform metal oxide structure is reported. We introduce a polymer polyacrylamide and a surfactant FSO into a sol-gel ink system, and the new ink system can gel from the printing pattern edge to center as temperature increases because of the cross-linking of the polymer chains. By that means, transport of solute molecules and solvent molecules is limited. Meanwhile, the surfactant can ensure that the solute in the central liquid phase deposits uniformly by enhancing the Marangoni flow during the gelation process. The ZrO2 film with uniform morphology was fabricated by drying and annealing the gelating film and afforded a leakage current density of 7.48 × 10-7 A cm-2 at 1 MV and a breakdown field of 1.9 MV cm-1 at an annealing temperature of 250 °C.

Circulating chemerin levels and gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Chemerin is a novel adipokine which is associated with metabolic syndrome and type 2 diabetes mellitus. However, recent investigations regarding circulating chemerin levels in gestational diabetes mellitus (GDM) are conflicting. This meta-analysis is to evaluate and determine their associations. METHODS: A systematic literature search was performed in PubMed, EMBASE and Web of Science up to 13 December 2017. Pooled standardized mean differences (SMD) and 95% confidence interval (CI) were calculated using a random-effect model. RESULTS: Eleven studies comprising 742 GDM patients and 840 normal pregnant women were included. Circulating chemerin levels were increased in GDM patients compared with healthy pregnant women (SMD: 1.16; 95% CI: 0.29, 2.04; P = 0.009). Subgroup analyses revealed such difference was especially available in the groups of the second trimester (SMD: 1.47; 95% CI: 0.28, 2.67) and mean age < 30 years (SMD: 2.30; 95% CI: 0.69, 3.91) of GDM patients. There was significant heterogeneity among studies (I2 = 98.0%, P < 0.001); however, heterogeneity disappeared or markedly decreased in the subgroups of European populations (I2 = 0.0%, P = 0.531), age ≥ 30 years (I2 = 28.2%, P = 0.223) and WHO diagnostic criteria (I2 = 0.0%, P = 0.490) when stratifying by study location, trimester of chemerin measurement and the diagnostic criteria of GDM. CONCLUSIONS: The elevated levels of circulating chemerin were associated with GDM, which suggests it might play an important role in the pathogenetic mechanism of GDM.

Bach1 Represses Wnt/ß-Catenin Signaling and Angiogenesis.

RATIONALE: Wnt/ß-catenin signaling has an important role in the angiogenic activity of endothelial cells (ECs). Bach1 is a transcription factor and is expressed in ECs, but whether Bach1 regulates angiogenesis is unknown. OBJECTIVE: This study evaluated the role of Bach1 in angiogenesis and Wnt/ß-catenin signaling. METHODS AND RESULTS: Hind-limb ischemia was surgically induced in Bach1(-/-) mice and their wild-type littermates and in C57BL/6J mice treated with adenoviruses coding for Bach1 or GFP. Lack of Bach1 expression was associated with significant increases in perfusion and vascular density and in the expression of proangiogenic cytokines in the ischemic hindlimb of mice, with enhancement of the angiogenic activity of ECs (eg, tube formation, migration, and proliferation). Bach1 overexpression impaired angiogenesis in mice with hind-limb ischemia and inhibited Wnt3a-stimulated angiogenic response and the expression of Wnt/ß-catenin target genes, such as interleukin-8 and vascular endothelial growth factor, in human umbilical vein ECs. Interleukin-8 and vascular endothelial growth factor were responsible for the antiangiogenic response of Bach1. Immunoprecipitation and GST pull-down assessments indicated that Bach1 binds directly to TCF4 and reduces the interaction of ß-catenin with TCF4. Bach1 overexpression reduces the interaction between p300/CBP and ß-catenin, as well as ß-catenin acetylation, and chromatin immunoprecipitation experiments confirmed that Bach1 occupies the TCF4-binding site of the interleukin-8 promoter and recruits histone deacetylase 1 to the interleukin-8 promoter in human umbilical vein ECs. CONCLUSIONS: Bach1 suppresses angiogenesis after ischemic injury and impairs Wnt/ß-catenin signaling by disrupting the interaction between ß-catenin and TCF4 and by recruiting histone deacetylase 1 to the promoter of TCF4-targeted genes.