Search

Abstract Background The prevalence of childhood obesity and overweight has risen globally, leading to increased rates of metabolic disorders. Various factors, including genetic, epigenetic, and environmental influences such as diet and physical activity, contribute to pediatric obesity. This study aimed to identify specific circulating miRNAs as potential biomarkers for assessing obesity in children. Methods Thirty children, including 15 obese and 15 extremely thin individuals, were selected for this study. MiRNA expression in circulating plasma was assessed using miRNA microarrays. The reliability of differential miRNA expression was confirmed using TaqMan qPCR. The correlation between miRNAs and obesity was analyzed through multiple linear regression, receiver operator characteristic (ROC) curve analysis, and odds ratio (OR) calculations. Bioinformatics tools were utilized to identify target genes for the selected miRNAs, and a functional network map was constructed. Results A total of 36 differentially expressed miRNAs were identified through gene chip analysis, and TaqMan qPCR validation confirmed the upregulation of seven miRNAs: hsa-miR-126-3p, hsa-miR-15b-5p, hsa-miR-199a-3p, hsa-miR-20a-5p, hsa-miR-223-3p, hsa-miR-23a-3p, and hsa-miR-24-3p. Among these, hsa-miR-15b-5p and hsa-miR-223-3p exhibited a statistically significant difference except for hsa-miR-23a-3p. These two miRNAs showed more predicted target genes related to obesity than others. Multiple linear regression analysis revealed an association between obesity and hsa-miR-15b-5p and hsa-miR-223-3p [10.529 (4.974–16.084), -10.225 (-17.852~ -2.657)]. Even after adjusting for age and sex, these two miRNAs remained associated with obesity [8.936 (3.572–14.301), -8.449(-15.634~ -1.303)]. The area under the ROC curve (AUC) reached values of 0.816, 0.711, and 0.929, respectively. Odds ratio analysis demonstrated a significant correlation between obesity and hsa-miR-15b-5p (OR = 143, 95% CI 5.80 to 56,313, p = 0.024) and between obesity and hsa-miR-223-3p (OR = 0.01, 95% CI 0.00 to 0.23, p = 0.037). Importantly, hsa-miR-15b-5p was found to have numerous target genes associated with the FoxO, insulin, Ras, and AMPK signaling pathways. Conclusions Differential miRNA expression profiles in the circulation of obese children compared to controls suggest underlying metabolic abnormalities. Hsa-miR-15b-5p and hsa-miR-223-3p may be considered as molecular markers for the screening of obese children and populations at risk of developing metabolic syndrome.

To break the narrow diversity bottleneck of the wheat D genome, a set of Aegilops tauschii-wheat introgression (A-WI) lines was developed by crossing Ae. tauschii accession T015 with common wheat elite cultivar Zhoumai 18 (Zhou18). A high-density genetic map was constructed based on Single Nucleotide Polymorphism (SNP) markers and 15 yield-related traits were evaluated in 11 environments for detecting quantitative trait loci (QTL). A total of 27 environmentally stable QTL were identified in at least five environments, 20 of which were derived from Ae. tauschii T015, explaining up to 24.27% of the phenotypic variations. The major QTL for kernel length (KL), QKl-2D.5, was delimited to a physical interval of approximately 2.6 Mb harboring 52 candidate genes. Three Kompetitive Allele Specific PCR (KASP) markers were successfully developed based on nonsynonymous nucleotide mutations of candidate gene AetT093_2Dv1G100900.1 and showed that A-WI lines with the T015 haplotype had significantly longer KL than the Zhou18 haplotype across all 11 environments. Four primary valuable A-WIs with good trait performance and carrying yield-related QTL were selected for breeding improvement. The results will facilitate the efficient transfer of beneficial genes from Ae. tauschii into wheat cultivars to improve wheat yield and other traits.

To explore the quality evaluation indicators of roasted macadamia nut kernels and establish a quality evaluation system, 21 samples of macadamia nuts roasted by different temperature and time duration were selected to determine with 16 quality indicators which included in browning index, moisture, total phenolic content, ABTS+ free radical scavenging activity ratio, acid value, peroxide value, hardness, fracture force, shear force and 7 sensory evaluations. These 16 indicators were comprehensively explored by correlation analysis, principal component analysis and cluster analysis to screen the critical indicators of quality evaluation for roasted kernels in macadamia nuts. As indicated by the research findings, with the augment of roasting temperature and time duration, the indicators including moisture, hardness, fracture force, shear force and sensory evaluation of hardness exhibited downturn trends, but the browning index, acid value, peroxide value, and the sensory evaluation of color, aroma, sweetness, bitterness, crispness, overall preference took on an overall upward trend. Aside from that, the total phenolic content and ABTS+ free radical scavenging activity ratio displayed changing trends of initial augment and subsequent reduction. As demonstrated by the results of correlation analysis on 16 indicators, 11 pairs of indicators had remarkable correlation (P

Abstract The immunogenicity of SARS-CoV-2 vaccines is poor in kidney transplant recipients (KTRs). The factors related to poor immunogenicity to vaccination in KTRs are not well defined. Here, observational study demonstrated no severe adverse effects were observed in KTRs and healthy participants (HPs) after first or second dose of SARS-CoV-2 inactivated vaccine. Different from HPs with excellent immunity against SARS-CoV-2, IgG antibodies against S1 subunit of spike protein, receptor-binding domain, and nucleocapsid protein were not effectively induced in a majority of KTRs after the second dose of inactivated vaccine. Specific T cell immunity response was detectable in 40% KTRs after the second dose of inactivated vaccine. KTRs who developed specific T cell immunity were more likely to be female, and have lower levels of total bilirubin, unconjugated bilirubin, and blood tacrolimus concentrations. Multivariate logistic regression analysis found that blood unconjugated bilirubin and tacrolimus concentration were significantly negatively associated with SARS-CoV-2 specific T cell immunity response in KTRs. Altogether, these data suggest compared to humoral immunity, SARS-CoV-2 specific T cell immunity response are more likely to be induced in KTRs after administration of inactivated vaccine. Reduction of unconjugated bilirubin and tacrolimus concentration might benefit specific cellular immunity response in KTRs following vaccination.

Protein tyrosine phosphatase 1B (PTP1B) is a key factor and regulator of glucose, lipid metabolism throughout the body, and a promising target for treatment of type 2 diabetes mellitus (T2DM). Gynostemma pentaphyllum is a famous oriental traditional medicinal herbal plant and functional food, which has shown many beneficial effects on glucose and lipid metabolism. The aim of the present study is to assess the inhibitory activity of five new and four known dammarane triterpenoids isolated from the hydrolysate product of total G. pentaphyllum saponins. The bioassay data showed that all the compounds exhibited significant inhibitory activity against PTP1B. The structure-activity relationship showed that the strength of PTP1B inhibitory activity was mainly related to the electron-donating group on its side chain. Molecular docking analysis suggested that its mechanism may be due to the formation of competitive hydrogen bonding between the electron-donating moiety and the Asp48 amino acid residues on the PTP1B protein.

Background The association between antipsychotics and cardiovascular diseases (CVDs) remains significant yet unestablished, especially in Chinese populations.Objective To investigate the risk of CVDs associated with antipsychotics among Chinese individuals with schizophrenia.Methods We conducted a nested case–control study on individuals diagnosed with schizophrenia in Shandong, China. The case group included individuals diagnosed with incident CVDs between 2012 and 2020. Each case was randomly matched with up to three controls. We used weighted logistic regression models to assess the risk of CVDs associated with antipsychotics and restricted cubic spline analysis to explore the dose–response relationship.Findings In total, 2493 cases and 7478 matched controls were included in the analysis. Compared with non-users, any antipsychotics use was associated with higher risk of any CVDs (weighted OR=1.54, 95% CI 1.32 to 1.79), with the risk mainly driven by ischaemic heart diseases (weighted OR=2.26, 95% CI 1.71 to 2.99). Treatments with haloperidol, aripiprazole, quetiapine, olanzapine, risperidone, sulpiride and chlorpromazine were associated with increased risk of CVDs. A non-linear dose–response relationship between dosage of antipsychotics and risk of CVDs was observed, with a sharp increase in risk in the beginning and then flattening out with higher doses.Conclusions Use of antipsychotics was associated with increased risk of incident CVDs among individuals with schizophrenia, and the risk varied substantially among different antipsychotics and specific CVDs.Clinical implications Clinicians should consider the cardiovascular risk of antipsychotics and choose the appropriate type and dose of drugs in the treatment of schizophrenia.

Abstract Ischemic stroke is a major cause of death and disability worldwide. Translation into the clinical setting of neuroprotective agents showing promising results in pre-clinical studies has systematically failed. One possible explanation is that the animal models used to test neuroprotectants do not properly represent the population affected by stroke, as most of the pre-clinical studies are performed in healthy young male mice. Therefore, we aimed to determine if the response to cerebral ischemia differed depending on age, sex and the presence of comorbidities. Thus, we explored proteomic and transcriptomic changes triggered during the hyperacute phase of cerebral ischemia (by transient intraluminal middle cerebral artery occlusion) in the brain of: (1) young male mice, (2) young female mice, (3) aged male mice and (4) diabetic young male mice. Moreover, we compared each group's proteomic and transcriptomic changes using an integrative enrichment pathways analysis to disclose key common and exclusive altered proteins, genes and pathways in the first stages of the disease. We found 61 differentially expressed genes (DEG) in male mice, 77 in females, 699 in diabetics and 24 in aged mice. Of these, only 14 were commonly dysregulated in all groups. The enrichment pathways analysis revealed that the inflammatory response was the biological process with more DEG in all groups, followed by hemopoiesis. Our findings indicate that the response to cerebral ischemia regarding proteomic and transcriptomic changes differs depending on sex, age and comorbidities, highlighting the importance of incorporating animals with different phenotypes in future stroke research studies.

Abstract Background Plant height (PH), spike length (SL) and spike compactness (SCN) are important agronomic traits in wheat due to their strong correlations with lodging and yield. Thus, dissection of their genetic basis is essential for the improvement of plant architecture and yield potential in wheat breeding. The objective of this study was to map quantitative trait loci (QTL) for PH, SL and SCN in a recombinant inbred line (RIL) population derived from the cross ‘PuBing3228 × Gao8901’ (PG-RIL) and to evaluate the potential values of these QTL to improve yield. Results In the current study, Five, six and ten stable QTL for PH, SL, and SCN, respectively, were identified in at least two individual environments. Five major QTL QPh.cas-5A.3, QPh.cas-6A, QSl.cas-6B.2, QScn.cas-2B.2 and QScn.cas-6B explained 5.58–25.68% of the phenotypic variation. Notably, two, three and three novel stable QTL for PH, SL and SCN were identified in this study, which could provide further insights into the genetic factors that shape PH and spike morphology in wheat. Conditional QTL analysis revealed that QTL for SCN were mainly affected by SL. Moreover, a Kompetitive Allele Specific PCR (KASP) marker tightly linked to stable major QTL QPh.cas-5A.3 was developed and verified using the PG-RIL population and a natural population. Conclusions Twenty-one stable QTL related to PH, SL, and SCN were identified. These stable QTL and the user-friendly marker KASP8750 will facilitate future studies involving positional cloning and marker-assisted selection in breeding.

IntroductionIdentification of stable major quantitative trait loci (QTLs) for yield-related traits is important for yield potential improvement in wheat breeding.MethodsIn the present study, we genotyped a recombinant inbred line (RIL) population using the Wheat 660K SNP array and constructed a high-density genetic map. The genetic map showed high collinearity with the wheat genome assembly. Fourteen yield-related traits were evaluated in six environments for QTL analysis.Results and DiscussionA total of 12 environmentally stable QTLs were identified in at least three environments, explaining up to 34.7% of the phenotypic variation. Of these, QTkw-1B.2 for thousand kernel weight (TKW), QPh-2D.1 (QSl-2D.2/QScn-2D.1) for plant height (PH), spike length (SL) and spikelet compactness (SCN), QPh-4B.1 for PH, and QTss-7A.3 for total spikelet number per spike (TSS) were detected in at least five environments. A set of Kompetitive Allele Specific PCR (KASP) markers were converted based on the above QTLs and used to genotype a diversity panel comprising of 190 wheat accessions across four growing seasons. QPh-2D.1 (QSl-2D.2/QScn-2D.1), QPh-4B.1 and QTss-7A.3 were successfully validated. Compared with previous studies, QTkw-1B.2 and QPh-4B.1 should be novel QTLs. These results provided a solid foundation for further positional cloning and marker-assisted selection of the targeted QTLs in wheat breeding programs.

Abstract Background Previous epidemiological studies have indicated the seasonal variability of serum lipid levels. However, little research has explicitly examined the separate secular and seasonal trends of dyslipidemia. The present study aimed to identify secular and seasonal trends for the prevalence of dyslipidemia and the 4 clinical classifications among the urban Chinese population by time series decomposition. Methods A total of 306,335 participants with metabolic-related indicators from January 2011 to December 2017 were recruited based on routine health check-up systems. Multivariate direct standardization was used to eliminate uneven distributions of the age, sex, and BMI of participants over time. Seasonal and trend decomposition using LOESS (STL decomposition) was performed to break dyslipidemia prevalence down into trend component, seasonal component and remainder component. Results A total of 21.52 % of participants were diagnosed with dyslipidemia, and significant differences in dyslipidemia and the 4 clinical classifications were observed by sex (P 23.9). Conclusions There were significant secular and seasonal features for dyslipidemia prevalence among the urban Chinese population. Different seasonal trends were found in the 4 clinical classifications of dyslipidemia. Precautionary measures should be implemented to control elevated dyslipidemia prevalence in specific seasons, especially in the winter and during traditional holidays.

Physical exercise benefits hippocampal function through various molecular mechanisms. Protein acetylation, a conserved and widespread post-translational modification, is involved in the synaptic plasticity and memory. However, whether exercise can change global acetylation and the role of acetylated proteins in the hippocampus have remained largely unknown. Herein, using healthy adult mice running for 6 weeks as exercise model and sedentary mice as control, we analyzed the hippocampal lysine acetylome and proteome by Liquid chromatography-tandem mass spectrometry. As a result, we profiled the lysine acetylation landscape for the hippocampus and identified 3,876 acetyl sites and 1,764 acetylated proteins. A total of 272 acetyl sites on 252 proteins were differentially regulated by chronic exercise, among which 18.58% acetylated proteins were annotated in mitochondria. These proteins were dominantly deacetylated and mainly associated with carbon-related metabolism, the Hippo signaling pathway, ribosomes, and protein processing. Meanwhile, 21 proteins were significantly expressed and enriched in the pathway of complement and coagulation cascades. Our findings provide a new avenue for understanding the molecular mechanisms underlying the benefits of exercise for hippocampal function and can contribute to the promotion of public health.

Purpose: To propose a novel, radiation-free method for postoperative three-dimensional (3D) position analysis of dental implants based on the dynamic navigation system (DNS) and evaluate its accuracy in vitro. Methods: A total of 60 implants were digitally planned and then placed in the standardized plastic models with a single-tooth gap and a free-end gap under the guidance of the DNS. Postoperative 3D positions of the inserted implants were evaluated using specially designed navigation-based software, and its datasets were superimposed onto those of cone beam computed tomography (CBCT) for accuracy analyses. Deviations at the coronal, apical, and angular levels were measured and statistically analyzed. Results: The mean 3D deviation was 0.88 ± 0.37 mm at the entry point and 1.02 ± 0.35 mm at the apex point. The mean angular deviation was 1.83 ± 0.79 degrees. No significant differences were noted in the deviations between implants placed in the single-tooth gap and the free-end situation (p > 0.05) or between different tooth positions at distal extensions (p > 0.05). Conclusions: This non-radiographic method provides facile, efficient, and reliable postoperative implant position evaluation and may be a potential substitute for CBCT, particularly for implants placed under the guidance of dynamic navigation.

Abstract Background High fat diet impact transcription of hepatic genes responsible for drug metabolism and pharmacokinetics. Until now, researches just focused on a couple specific genes without a global profile showing. Age-dependent manner was also not noted well. This study aims to investigate the high fat diet effect on transcriptome of drug metabolism and pharmacokinetic system in mouse livers and show the age-dependent evidence. Methods C57BL/6 male mice were used in this experiment. High fat diet was used to treat mice for 16 and 38 weeks. Serum total cholesterol, low density lipoprotein cholesterol, aspartate transaminase, and alanine transaminaselevels were measured. Meanwhile, Histology, RNA-Seq, RT-PCR analysis and fourteen major hepatic bile acids quantification were performed for the liver tissues. Data was mined at levels of genes, drug metabolism and pharmacokinetic sysem, and genome wide. Results Treatment with high fat diet for 38 weeks significantly increased levels of serum lipids as well as aspartate transaminase, and alanine transaminase. Meanwhile, lipid accumulation in livers was observed. At week 38 of the experiment, the profile of 612 genes involved in drug metabolism and pharmacokinetics was significantly changed, indicated by a heatmap visulization and a principal component analysis. In total 210 genes were significantly regulated. Cyp3a11, Cyp4a10, and Cyp4a14 were down-regulated by 10–35 folds, while these three genes also were highly expressed in the liver. High fat diet regulated 11% of genome-wide gene while 30% of genes involved in the hepatic drug metabolism and pharmacokinetic system. Genes, including Adh4, Aldh1b1, Cyp3a11, Cyp4a10, Cyp8b1, Fmo2, Gsta3, Nat8f1, Slc22a7, Slco1a4, Sult5a1, and Ugt1a9, were regulated by high fat diet as an aging-dependent manner. Bile acids homeostasis, in which many genes related to metabolism and transportation were enriched, was also changed by high fat diet with an aging-dependet manner. Expression of genes in drug metabolism and disposition system significantly correlated to serum lipid profiles, and frequently correlated with each other. Conclusions High fat diet changed the global transcription profile of hepatic drug metabolism and pharmacokinetic system with a age-dependent manner.

Purpose: To compare the U-tube and cusp dynamic navigation system registration methods in the use of dental implant placement, and to assess the influence of the location of missing teeth on these registrations. Methods: 32 resin mandible models and 64 implants were utilized, with implants being placed using one of the two registration methods selected at random. Accuracy was measured through the superimposition of the final and planned implant positions. Angular deviation, 3D entry deviation, and 3D apex deviation were analyzed. Results: The overall mean 3D deviation was 1.089 ± 0.515 mm at the entry point and 1.174 ± 0.531 mm at the apex point, and mean angular deviation was 1.970 ± 1.042 degrees. No significant difference (p > 0.05) was observed when comparing these two registration methods. However, the U-tube method showed significant difference when assessing the location of missing teeth (without distal-extension absence and distal-extension absence), whereas cusp registration was unaffected. Conclusions: Both the U-tube and cusp dynamic navigation system registration methods are accurate when implemented in vitro. Besides, the cusp registration technique can also overcome several of the limitations of the U-tube approach and the accuracy of it was not influenced by the location of the missing teeth, highlighting it as a method worthy of further clinical research.

Triadimefon is a broad-spectrum fungicide widely applied in the agriculture. It is believed to be an endocrine disruptor. Whether triadimefon can inhibit the development of fetal Leydig cells and the underlying mechanisms are unknown. Thirty-two female pregnant Sprague-Dawley rats were randomly assigned into four groups and were dosed via gavage of triadimefon (0, 25, 50, and 100 mg/kg/day) for 9 days from gestational day (GD) 12–20. Triadimefon significantly reduced serum testosterone level in male fetuses at 100 mg/kg. The double immunofluorescence staining of proliferating cell nuclear antigen (PCNA) and cytochrome P450 cholesterol side-chain cleavage (a biomarker for fetal Leydig cells) was used to measure PCNA-labeling in fetal Leydig cells. It markedly increased fetal Leydig cell number primarily via increasing single cell population and elevated the PCNA-labeling of fetal Leydig cells in male fetuses at 100 mg/kg while it induced abnormal aggregation of fetal Leydig cells. The expression levels of fetal Leydig cell genes, Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Insl3 and Nr5a1, were determined to explore its effects on fetal Leydig cell development. We found that triadimefon markedly down-regulated the expression of Leydig cell genes, Hsd17b3, Insl3, and Nr5a1 as low as 25 mg/kg and Scarb1 and Cyp11a1 at 100 mg/kg. It did not affect Sertoli cell number but markedly down-regulated the expression of Sertoli cell gene Amh at 50 and 100 mg/kg. Triadimefon significantly down-regulated the expression of antioxidant genes Sod1, Gpx1, and Cat at 25–100 mg/kg, suggesting that it can induce oxidative stress in fetal testis, and it reduced the phosphorylation of ERK1/2 and AKT2 at 100 mg/kg, indicating that it can inhibit the development of fetal Leydig cells. In conclusion, gestational exposure to triadimefon inhibits the development of fetal Leydig cells in male fetuses by inhibiting its differentiation.

Strokes are the second most common cause of death worldwide and a leading cause of disability. Regular consumption of polyphenols has been shown to reduce the risk of suffering a cardiovascular event. For this reason, we have investigated the protective effect of Salicornia ramosissima, a seasonal halophyte that synthetizes high amounts of bioactive compounds, including polyphenols, in response to environmental stress. Aqueous, hydroalcoholic, and ethanolic extracts were prepared to investigate if dietary supplementation prior to ischemic challenge can prevent subsequent damage using two animal models. First, we screened the protective effect against hypoxia–reoxygenation in Drosophila melanogaster and observed that both ethanolic and hydroalcoholic extracts protected flies from the deleterious effects of hypoxia. Second, we confirmed the protective effect of S. ramosissima ethanolic extract against brain ischemia using the transient middle cerebral artery occlusion mice model. Four weeks of oral supplementation with the ethanolic extract before artery occlusion reduced infarct volume and lowered the plasma levels of the DNA peroxidant product 8-hydroxydeoxyguanosine. Phytochemical profiling of S. ramosissima ethanolic extract revealed 50 compounds. Thus, it represents a valuable source of bioactive compounds that show promising disease-modifying activities and could be further developed as an effective food supplement for the prevention or treatment of neurovascular disorders.

Abstract Background Wilms’ tumor is also called nephroblastoma and is the most common pediatric renal cancer. Several genetic and epigenetic factors have been found to account for the development of Wilms’ tumor. MiRNAs play important roles in this tumorigenic process. In the present study, we aimed to investigate the role of miR-140-5p in nephroblastoma by identifying its targets, as well as its underlying molecular mechanism of action. Methods The miRNA expression profile of nephroblastoma samples was investigated and the targets of miR-140-5p were predicted and validated using the miRNA luciferase reporter method. Moreover, the roles of miR-140-5p in regulating nephroblastoma cell proliferation, migration and cell cycle were analyzed by the CCK8, migration and flow cytometry assays, respectively. The downstream protein of the direct target of miR-140-5p was also identified. Results miR-140-5p was downregulated in Wilms’ tumor tissues, whereas in the nephroblastoma cell lines G401 and WT-CLS1 that exhibited high levels of miRNA-140-5p, inhibition of cellular proliferation and metastasis were noted as well as cell cycle arrest at the G1/S phase. TGFBRI and IGF1R were identified as direct target genes for miRNA-140-5p. In addition, SMAD2/3 and p-AKT were regulated by TGFBRI and IGF1R separately and participated in the miRNA-140-5p regulatory network. Ectopic expression of TGFBR1 and IGF-1R could abrogate the inhibitory effect of miR-140-5p. Conclusion We demonstrated that miRNA-140-5p participates in the progression of Wilms’ tumor by targeting the TGFBRI/SMAD2/3 and the IGF-1R/AKT signaling pathways.

After stroke and other brain injuries, there is a high incidence of respiratory complications such as pneumonia or acute lung injury. The molecular mechanisms that drive the brain-lung interaction post-stroke have not yet been elucidated. We performed transient middle cerebral artery occlusion (MCAO) and sham surgery on C57BL/6J mice and collected bronchoalveolar lavage fluid (BALF), serum, brain, and lung homogenate samples 24 h after surgery. A 92 proteins-panel developed by Olink Proteomics® was used to analyze the content in BALF and lung homogenates. MCAO animals had higher protein concentration levels in BALF than sham-controls, but these levels did not correlate with the infarct volume. No alteration in alveolar-capillary barrier permeability was observed. A total of 12 and 14 proteins were differentially expressed between the groups (FDR < 0.1) in BALF and lung tissue homogenates, respectively. Of those, HGF, TGF-α, and CCL2 were identified as the most relevant to this study. Their protein expression patterns were verified by ELISA. This study confirmed that post-stroke lung damage was not associated with increased lung permeability or cerebral ischemia severity. Furthermore, the dysregulation of HGF, TGF-α, and CCL2 in BALF and lung tissue after ischemia could play an important role in the molecular mechanisms underlying stroke-induced lung damage.

This paper aims to collect a compendium of randomized controlled trials (RCTs) exploring the effects of cognitively engaging physical activity (PA) interventions (basketball and floorball) on various domain-specific executive functions (EFs) in children aged 4 to 12. Following the PRISMA principle, 11 articles (total sample size: 2053) were analyzed for effect size and moderating impact with Stata 13.0 software. Overall EFs (SMD = 0.21, 95% CI 0.10 to 0.32, p < 0.05), updating (SMD = 0.17, 95% CI 0.03 to 0.30, p < 0.05) and shifting (SMD = 0.32, 95% CI 0.02 to 0.61, p < 0.05) were enhanced by cognitively engaging PA interventions. Age and BMI were found to have no effect on overall EFs performance in Meta regression. Overall EFs performance was improved by interventions with a session length (≥35 min) (SMD = 0.30, 95 % CI 0.10 to 0.49, p = 0.033). The review suggests that despite the moderate effect sizes, cognitively engaging PA may be an effective approach to improving EFs in children aged 4 to 12, especially updating and shifting.

Background: Nasopharyngeal carcinoma (NPC) is common in Southern China. The molecular mechanism underlying NPC genesis and progression has been comprehensively investigated, but the key gene (s) or pathway (s) pertaining to NPC are unidentified. Methods: We explored some key genes and pathways involved in NPC through using meta-analysis of deposited expression of microarray data of NPC. The expression of proliferating cell nuclear antigen clamp associated factor (PCLAF) was determined by real-time PCR and western blots. CCK-8 assay, colony formation assay, transwell migration assay, cell wound healing assay, cell cycle analysis and cell apoptosis were carried out to assess biological behaviors caused by downregulation and overexpression of PCLAF in vitro. CHIP was utilized to determine the direct upstream regulatory transcription factors of PCLAF. Results: PCLAF was the key gene of NPC, which was significantly up-regulated in NPC cell line compared to the normal nasopharyngeal cell line. Additionally, in vitro assay has demonstrated the down-regulation and overexpression of PCLAF, resulted in significantly suppressed and enhanced NPC proliferation, metastasis and invasion respectively. Furthermore, the up-regulation of PCLAF in NPC is induced by direct binding of dysregulated NF-κB p50/RelB complex to the promoter of PCLAF. Conclusion: Our results offer a strategy for re-using the deposited data to find the key genes and pathways involved in pathogenesis of cancer. Our study has provided evidence of supporting the role of PCLAF in NPC genesis and progression.

Abstract Background Folic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia. We hypothesized that FA supplementation prevents cardiac fibrosis and cardiac dysfunction induced by obesity. Methods Six-week-old C57BL6/J mice were fed a high-fat diet (HFD), normal diet (ND), or an HFD supplemented with folic acid (FAD) for 14 weeks. Cardiac function was measured using a transthoracic echocardiographic exam. Phenotypic analysis included measurements of body and heart weight, blood glucose and tissue homocysteine (Hcy) content, and heart oxidative stress status. Results HFD consumption elevated fasting blood glucose levels and caused obesity and heart enlargement. FA supplementation in HFD-fed mice resulted in reduced fasting blood glucose, heart weight, and heart tissue Hcy content. We also observed a significant cardiac systolic dysfunction when mice were subjected to HFD feeding as indicated by a reduction in the left ventricular ejection fraction and fractional shortening. However, FAD treatment improved cardiac function. FA supplementation protected against cardiac fibrosis induced by HFD. In addition, HFD increased malondialdehyde concentration of the heart tissue and reduced the levels of antioxidant enzyme, glutathione, and catalase. HFD consumption induced myocardial oxidant stress with amelioration by FA treatment. Conclusion FA supplementation significantly lowers blood glucose levels and heart tissue Hcy content and reverses cardiac dysfunction induced by HFD in mice. These functional improvements of the heart may be mediated by the alleviation of oxidative stress and myocardial fibrosis.

Abstract Background To describe the characteristics of patients with syphilitic uveitis in northern China. Methods A case series of 21 patients (33 eyes) diagnosed with syphilitic uveitis from 2011 to 2016 at a tertiary center in northern China was retrospectively analyzed. Results Twenty-one patients (33 eyes) were diagnosed as syphilitic uveitis. Posterior segment involvement was found in 32 eyes (97.0%). Vitreous haze, neuroretinitis, and posterior placoid chorioretinitis were mainly found in patients with a relatively short duration of the disease, while diffuse chorioretinitis, pseudoretinitis pigmentosa, cystoid macular edema, and epiretinal membrane were found in patients with relatively long duration of ocular involvement. A low best-corrected visual acuity (P = 0.022) and a delay of syphilis treatment (P < 0.001) were associated with a significantly worse visual outcome. Conclusions Syphilitic uveitis should be included in the differential diagnosis of any form of posterior ocular inflammation. The pattern of ocular involvement may change with the disease progression.

Background/Aims: Obesity is a major contributor to the growing prevalence of metabolic and cardiovascular diseases. This study was designed to investigate the effect of folic acid (FA) on obese mice by detecting the genome-wide expression profile of lncRNAs and mRNAs in the heart. Methods: Heart samples were collected from mice fed with standard diet (SD), high-fat diet (HFD) and high-fat diet with FA intake (HFDF). LncRNAs and mRNAs between HFD and HFDF group were analyzed by lncRNA microarray. Nine lncRNAs and mRNAs were validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics prediction was used to investigate the potential function of these differentially expressed lncRNAs. Co-expresson analysis was used to determine the transcriptional regulatory relationship of differentially expressed lncRNAs and mRNAs between two groups. Results: The expression of 58,952 lncRNAs and 20,145 mRNAs in HFD and HFDF groups was profiled by using microarrays. Gene Ontology and pathway analyses indicated that the biological functions of differentially expressed mRNAs were related to inflammation, energy metabolism, and cell differentiation. Co-expression networks composed of lncRNAs and mRNAs were also constructed to investigate the potential regulatory roles of differentially expressed lncRNAs on mRNAs. LncRNAs, namely, NONMMUT033847, NONMMUT070811, and NONMMUT015327, were validated through qRT-PCR, and these lncRNAs may be important factors regulating inflammation, energy metabolism, and cell differentiation. The expression levels of Dnajb1, Egr2, Hba-a1, Il1β, Cxcl2, and Tnfsf9 were significantly different between HFD and HFDF. Conclusions: Results suggested that FA may improve the cardiovascular function of obesity and contribute to those lncRNAs associated with inflammation and cell differentiation. In a nutshell, the present study identified a panel of lncRNAs and mRNAs that may be potential biomarkers or drug targets relevant to the high-fat diet related obesity.

Background. Genome-wide association studies have found an obesity-related single-nucleotide polymorphism rs10938397 near the glucosamine-6-phosphate deaminase 2 gene (GNPDA2) encoding, an enzyme that catalyzes the deamination of the glucosamine-6-phosphate involved in the hexosamine signaling pathway, but the molecular mechanisms underlying the missing link between GNPDA2 and obesity remain elusive. Methods. As obesity is accompanied by an increase in the size and the number of adipocytes, the present study investigates the possible mechanism of the GNPDA2 in adipogenesis using GeneChip® Human Transcriptome Array 2.0 in human adipose-derived mesenchymal stem cells. Results. We found that overexpression of GNPDA2 enhanced accumulation of lipid droplets, and knocking down the gene decreased accumulation of lipid droplets. GO term enrichment analysis indicated that most differentially expressed genes (DEGs) affected by deficiency of GNPDA2 have functions to lipid and glucose metabolism. Further KEGG enrichment analysis showed that the greatest proportion of DEGs are involved in thermogenesis, peroxisome proliferator-activated receptor (PPAR) signaling pathway, carbon metabolism, and fatty acid metabolism including fatty acid degradation, elongation, and biosynthesis. Conclusion. These findings suggest that GNPDA2 may be a critical gene for lipid and glucose metabolism, and the expression level of GNPDA2 alters the transcriptome profile of human adipose-derived mesenchymal stem cells.

New neuroreparative and neuroprotective therapies are being sought to treat stroke patients. One approach is the remodeling of extracellular matrix, which participates in both brain injury and neurovascular repair when matrix metalloproteinases (MMPs) are thought to be key players. Our aim was to investigate the role of MMP-13 (collagenase-3) in the acute (24 h and 3 days) and delayed (2 weeks) phases of stroke. Permanent and transient cerebral ischemia models involving the cortex were induced in MMP-13 knock-out (KO) and wild-type (WT) mice. In the transient model, MMP-13 deficiency reduced the amount of TTC-stained infarct tissue, reduced hemorrhagic events and improved functional outcomes (p

At present, most of released wheat cultivars or breeding lines in China are susceptible to powdery mildew (Pm) (caused by Blumeria graminis f. sp. tritici, Bgt), so there is an urgent need to rapidly transfer effective and broad-spectrum Pm resistance genes into elite cultivars/lines. Near-isogenic lines (NILs) with short target gene region are very important in molecular breeding and map-based cloning and can be developed by combining marker-assisted selection and conventional phenotypic identification. However, no Pm gene NILs were reported by using this method in the previous studies. A new broad-spectrum dominant resistance gene Pm2b, derived from the Chinese wheat breeding line KM2939, conferred high resistance to Pm at both the seedling and adult stages. In this study, with the aid of forward and background selection (FS and BS) using molecular markers, the Pm2b gene was introgressed into three elite susceptible commercial cultivars Shimai 15, Shixin 828, and Kenong 199 through the back-crossing procedure. With the appropriate backcrossing generations, selected population sizes and marker number for BS, the homozygous resistant BC3F2:3 NILs of Pm2b gene in the three genetic backgrounds with the highest recipient genome composition of about 99%, confirmed by simple sequence repeat markers and 660K single nucleotide polymorphic array, were developed and evaluated for the powdery mildew resistance and agronomic traits. The different resistance and similar or improved agronomic performance between Pm2b NILs and their corresponding recurrent parents indicated their potential value in the marker-assisted breeding of the Pm2b gene. Moreover, the development of four flanked diagnostic markers (CFD81, BWM25, BWM20, and BWM21) of the Pm2 gene can effectively assist the forward selection and accelerate the transfer and use of this resistance gene.

MicroRNAs (miRNAs) are important post-transcriptional regulators during adipocyte adipogenesis. MiR-206-3p, a tissue-specific miRNA, is absent in white adipocytes. In this study, we examined the roles of mmu-miR-206-3p in the adipogenic differentiation of 3T3-L1 preadipocytes. The miR-206-3p expression has shown an apparent decreasing trend after induction, and sustained low expression throughout the differentiation of 3T3-L1 cells. miR-206-3p blocked the adipogenic differentiation of 3T3-L1 cells by attenuating c-Met expression; the inhibition effect of miR-206 to the adipogenic differentiation can be counteracted by restoring c-Met expression. In addition, miR-206-3p decreased the phosphorylation of Akt, which is the downstream effector of c-Met in the PI3K/Akt signaling pathway. These data indicate that miR-206-3p inhibits adipocyte adipogenesis through silencing c-Met and subsequently inactivating the PI3K/Akt signaling pathway.

Interleukin-6 (IL-6) is an important cytokine participating in multiple biologic activities in immune regulation and inflammation. IL-6 has been associated with cardiovascular remodeling. However, the mechanism of IL-6 in hypertensive cardiac fibrosis is still unclear. Angiotensin II (Ang II) infusion in mice increased IL-6 expression in the heart. IL-6 knockout (IL-6-/-) reduced Ang II-induced cardiac fibrosis: 1) Masson trichrome staining showed that Ang II infusion significantly increased fibrotic areas of the wild-type mouse heart, which was greatly suppressed in IL-6-/- mice and 2) immunohistochemistry staining showed decreased expression of α-smooth muscle actin (α-SMA), transforming growth factor β1 (TGF-β1) and collagen I in IL-6-/- mouse heart. The baseline mRNA expression of IL-6 in cardiac fibroblasts was low and was absent in cardiomyocytes or macrophages; however, co-culture of cardiac fibroblasts with macrophages significantly increased IL-6 production and expression of α-SMA and collagen I in fibroblasts. Moreover, TGF-β1 expression and phosphorylation of TGF-β downstream signal Smad3 was stimulated by co-culture of macrophages with cardiac fibroblasts, while IL-6 neutralizing antibody decreased TGF-β1 expression and Smad3 phosphorylation in co-culture of macrophage and fibroblast. Taken together, our results indicate that macrophages stimulate cardiac fibroblasts to produce IL-6, which leads to TGF-β1 production and Smad3 phosphorylation in cardiac fibroblasts and thus stimulates cardiac fibrosis.