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Introduction: Cardiac hypertrophy is an important contributor of heart failure, and the mechanisms remain unclear. Leucine zipper protein 1 (LUZP1) is essential for the development and function of cardiovascular system; however, its role in cardiac hypertrophy is elusive. Objectives: This study aims to investigate the molecular basis of LUZP1 in cardiac hypertrophy and to provide a rational therapeutic approach. Methods: Cardiac-specific Luzp1 knockout (cKO) and transgenic mice were established, and transverse aortic constriction (TAC) was used to induce pressure overload-induced cardiac hypertrophy. The possible molecular basis of LUZP1 in regulating cardiac hypertrophy was determined by transcriptome analysis. Neonatal rat cardiomyocytes were cultured to elucidate the role and mechanism of LUZP1 in vitro. Results: LUZP1 expression was progressively increased in hypertrophic hearts after TAC surgery. Gain- and loss-of-function methods revealed that cardiac-specific LUZP1 deficiency aggravated, while cardiac-specific LUZP1 overexpression attenuated pressure overload-elicited hypertrophic growth and cardiac dysfunction in vivo and in vitro. Mechanistically, the transcriptome data identified Stat3 pathway as a key downstream target of LUZP1 in regulating pathological cardiac hypertrophy. Cardiac-specific Stat3 deletion abolished the pro-hypertrophic role in LUZP1 cKO mice after TAC surgery. Further findings suggested that LUZP1 elevated the expression of Src homology region 2 domain-containing phosphatase 1 (SHP1) to inactivate Stat3 pathway, and SHP1 silence blocked the anti-hypertrophic effects of LUZP1 in vivo and in vitro. Conclusion: We demonstrate that LUZP1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling, and targeting LUZP1 may develop novel approaches to treat pathological cardiac hypertrophy.

Objective To explore the association of urinary heme oxygenase 1 （HO-1） with renal damage and lupus activity in patients with systemic lupus erythematosus （SLE） and determine the value of urinary HO-1 in the diagnosis and activity estimation of lupus nephritis （LN）. Methods A total of 65 patients with confirmed SLE were assigned into two groups of LN （n = 40） and non-LN （n = 25） according to whether or not there was renal damage. Urinary HO-1 was measured by enzyme-linked immunosorbent assay （ELISA） while the level of disease activity assessed by SLE Disease Activity Score （SLEDAI）. Urinary HO-1 level and other clinical data were compared between two groups. Logistic regression was utilized for examining the risk factors of LN and receiver operating characteristic （ROC） curve plotted for determining the diagnostic efficacy of urinary HO-1 for renal damage. Results Urinary HO-1 level in patients with renal damage was significantly higher than that without renal damage [（740.42 ± 86.98）ng/L vs （679.03 ± 61.33）ng/L, P = 0.003]. Urinary HO-1 level was correlated positively with SLEDAI, serum creatinine and urinary protein while negatively with glomerular filtration rate and creatinine clearance rate. Urinary HO-1, IgG, hypocomplementemia and hematuria were independent risk factors for LN （AUC = 0.853,95%CI: 0.753-0.953）. Area under the ROC curve for HO-1 alone was 0.710. When HO-1 was 721 ng/L, Youden index reached the optimal cut-off value. Conclusion Urine HO-1 level is significantly elevated in SLE patients with renal damage and it is associated with lupus activity. And HO-1 has clinical value in determining renal damage and disease activity in SLE patients.

Objective To evaluate the effect of chronic disease health management on disease activity and renal injury in patients with lupus nephritis (LN). Methods A total of 97 LN patients diagnosed with lupus nephritis were randomizedly assigned to into two groups of chronic disease health management (n=49) and conventional management (n=48). and followed up for a median of 6 months. The disease activity index (SLEDAI), and blood and urinarye parameters and medicine compliance and living quality-of-life (SF-36) and trust in doctor physician were recordedobserved in at Month 6.Results Patients who managed by of chronic disease health management had lower disease activity compared to conventional group (P

Background: No single risk factor is decisive in shaping an individual's healthy development. This study aimed to analyze the relationship between depressive symptoms and a cumulative risk index comprising individual, family, and social variables among nursing students. Methods: We enrolled 1716 Chinese nursing students from three universities in a paperless survey that assessed a range of individual, family, and social risk factors associated with depressive symptoms. Multiple risk analysis was conducted to create a composite risk score for each individual. A test for trend was employed to assess the relationship between the multiple risk classification and depressive symptoms individually. Additionally, a 2-step cluster analysis and χ2 tests were used to examine the relationship between the different clusters and the level of depressive symptoms. Results: The mean scores of depressive symptoms increased significantly as the number of risk factors increased, regardless of their combination. As the number of risk factors increased, the proportion of nursing students in the normal group decreased, while the proportion in the group with depressive symptoms of varying severity tended to increase (P

ABSTRACTPreeclampsia (PE), a pregnancy-specific syndrome, has been associated with the gut bacteriome. Here, to investigate the impact of the gut virome on the development of PE, we identified over 8,000 nonredundant viruses from the fecal metagenomes of 40 early-onset PE and 37 healthy pregnant women and profiled their abundances. Comparison and correlation analysis showed that PE-enriched viruses frequently connected to Blautia species enriched in PE. By contrast, bacteria linked to PE-depleted viruses were often the Bacteroidaceae members such as Bacteroides spp., Phocaeicola spp., Parabacteroides spp., and Alistipes shahii. In terms of viral function, PE-depleted viruses had auxiliary metabolic genes that participated in the metabolism of simple and complex polysaccharides, sulfur metabolism, lipopolysaccharide biosynthesis, and peptidoglycan biosynthesis, while PE-enriched viruses had a gene encoding cyclic pyranopterin monophosphate synthase, which seemed to be special, that participates in the biosynthesis of the molybdenum cofactor. Furthermore, the classification model based on gut viral signatures was developed to discriminate PE patients from healthy controls and showed an area under the receiver operating characteristic curve of 0.922 that was better than that of the bacterium-based model. This study opens up new avenues for further research, providing valuable insights into the PE gut virome and offering potential directions for future mechanistic and therapeutic investigations, with the ultimate goal of improving the diagnosis and management of PE.IMPORTANCEThe importance of this study lies in its exploration of the previously overlooked but potentially critical role of the gut virome in preeclampsia (PE). While the association between PE and the gut bacteriome has been recognized, this research takes a pioneering step into understanding how the gut virome, represented by over 8,000 nonredundant viruses, contributes to this condition. The findings reveal intriguing connections between PE-enriched viruses and specific gut bacteria, such as the prevalence of Blautia species in individuals with PE, contrasting with bacteria linked to PE-depleted viruses, including members of the Bacteroidaceae family. These viral interactions and associations provide a deeper understanding of the complex dynamics at play in PE.

BackgroundAdvanced schistosomiasis is the most serious outcome of infection and has a negative impact on both physical fitness and mental health of patients, the latter of which has long been overlooked. Therefore, we performed this systematic review and meta-analysis to estimate the overall prevalence of depressive symptoms, one of the most common mental problems, in patients with advanced schistosomiasis in China.MethodsSix electronic databases were searched for studies reporting the prevalence of depressive symptoms in the targeted patients. Assessments were pooled using a fixed- or random-effects model based on heterogeneity test. Subgroup analyses were further performed and differences between/among groups were examined using the chi-squared test. The protocol had previously been registered in PROSPERO (CRD42023406708).ResultsA total of 11 studies with 1,673 participants were included. The pooled prevalence of depressive symptoms in advanced schistosomiasis in China was 62.01% (95% CI: 51.30% - 72.72%), with a significant heterogeneity among studies. Depressive symptoms were more prevalent in patients with complications and more than half of the patients suffered a mild- or moderate-level of depression. No publication bias was found, and sensitivity analysis showed a stable result.ConclusionsThe overall prevalence of depressive symptoms in advanced schistosomiasis in China was high enough to warrant psychotherapeutic interventions, especially for patients with complications. This would greatly prevent or/and reduce depression and improve their quality of life.

Objective To explore the relevance between neutrophil-to-lymphocyte ratio (NLR) and renal injury in patients with primary Sjogren's syndrome (pSS) and evaluate the clinical application value of NLR in renal injury of pSS. Methods From January 2017 to June 2022, the relevant clinical data were retrospectively reviewed for 134 hospitalized pSS patients. Based upon the presence or absence of renal injury, they were assigned into two groups of pSS with renal injury and pSS without renal injury. NLR and other laboratory parameters were compared between two groups. Through Spearman's rank correlation analysis, the correlations were examined between NLR and renal injury parameters (creatinine, urea nitrogen, uric acid, cystatin C & glomerular filtration rate) and inflammation-related parameters (erythrocyte sedimentation rate & C-reactive protein). The risk factors of renal injury were explored by multivariate Logistic regression. Receiver operating characteristic (ROC) curve was utilized for comparing the diagnostic efficacy of NLR, renal injury parameters and inflammation-related parameters for renal injury in pSS. Results NLR was markedly elevated in renal injury group than that in renal non-injury group (P

Objective To lay the groundwork for formulating novel immunotherapies through understanding the regulatory role of ferroptosis and its function in immune microenvironment in ANCA-associated vasculitis (AAV) with renal injury. Methods Kidney data sets on AAV were downloaded from the database of Gene Expression Omnibus (GEO). Based upon the results of differential expression, consensus clustering algorithm was employed for identifying the subtypes of iron mortality. Single sample gene set enrichment analysis (ssGSEA) and gene set variation analysis (GSVA) were performed for evaluating the immune invasion and signaling pathways of subtypes. Key ferroptosis-related genes (FRGs) were further screened by LASSO and SVM-RFE algorithms and verified by independent data sets. CIBERSORT was utilized for assessing the abundance of infiltrating immune cells for FRGs. Finally a clinical diagnostic model of FRGs was constructed by rsm package. And the correlation between FRGs and renal function was examined by Nephroseq V5 database. Results Twenty-four ferroptosis related genes were significantly differentially expressed in AAV with kidney injury. Unsupervised cluster analysis revealed the regulatory patterns of two different ferroptosis subtypes with significant differences in gene expression, immune infiltration and biological functional pathways. A set of FRGs composed of ALOX5, CD44, CRYAB, TP53, and FTH1 was selected by two machine learning algorithms. It could effectively distinguish AAV with kidney injury from normal control group. CCR, macrophage and HLA were correlated positively with FRGs. Area under ROC curve of clinical diagnostic model constructed by FRGs was 0. 961. FRGs were correlated negatively with glomerular filtration rate (GFR). However, except for CRYAB and FTH1, other FRGs were correlated positively with serum creatinine (Scr). It implicated their potential relevance to renal injury in ANCA-associated vasculitis (AAV) and their potential as prognostic biomarkers. Conclusions Ferroptosis in AAV with kidney injury is correlated closely with immune microenvironment. It provides rationales for devising new treatments for AAV with kidney injury through a better understanding the pattern of ferroptosis.

Abstract Background To date, data on the efficacy of targeted therapies for mucosal melanoma (MM) are limited. In this study, we analyzed genetic alterations according to the primary site of origin, which could provide clues for targeted therapy for MM. Methods We conducted a retrospective cohort study of 112 patients with MM. Targeted sequencing was performed to analyze genetic aberrations. Kaplan–Meier analysis was conducted with the log-rank test to compare the significance among subgroups. Results In total, 112 patients with MM were included according to the anatomic sites: 38 (33.9%) in the head and neck, 22 (19.6%) in the genitourinary tract, 21 (18.8%) in the anorectum, 19 (17.0%) in the esophagus, 10 (8.9%) in the uvea, and 2 (1.8%) in the small bowel. The most significantly mutated genes included BRAF (17%), KIT (15%), RAS (15%), TP53 (13%), NF1 (12%), SF3B1 (11%), GNA11 (7%), GNAQ (5%), and FBXW7 (4%). A large number of chromosomal structural variants was found. The anatomic sites of esophagus and small bowel were independent risk factors for progression-free survival (PFS, hazard ratio [HR] 4.78, 95% confidence interval [CI] 2.42–9.45, P

Abstract Background Cysteine dioxygenase 1 (CDO1) is frequently methylated, and its expression is decreased in many human cancers including breast cancer (BC). However, the functional and mechanistic aspects of CDO1 inactivation in BC are poorly understood, and the diagnostic significance of serum CDO1 methylation remains unclear. Methods We performed bioinformatics analysis of publicly available databases and employed MassARRAY EpiTYPER methylation sequencing technology to identify differentially methylated sites in the CDO1 promoter of BC tissues compared to normal adjacent tissues (NATs). Subsequently, we developed a MethyLight assay using specific primers and probes for these CpG sites to detect the percentage of methylated reference (PMR) of the CDO1 promoter. Furthermore, both LentiCRISPR/dCas9‐Tet1CD‐based CDO1‐targeted demethylation system and CDO1 overexpression strategy were utilized to detect the function and underlying mechanism of CDO1 in BC. Finally, the early diagnostic value of CDO1 as a methylation biomarker in BC serum was evaluated. Results CDO1 promoter was hypermethylated in BC tissues, which was related to poor prognosis (p

Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy of the skin, and its incidence is increasing annually. Once cSCC becomes metastatic, its associated mortality rate is much higher than that of cSCC in situ. However, the current treatments for progressive cSCC have several limitations. The aim of this study was to suggest a potential compound for future research that may benefit patients with cSCC. Methods: In this study, we screened the following differentially expressed genes from the Gene Expression Omnibus database: GSE42677, GSE45164, GSE66359, and GSE98767. Using strategies such as protein-protein interaction network analysis and the CYTOSCAPE plugin MCODE, key modules were identified and then verified by Western blotting. Subsequently, related signalling pathways were constituted in the SIGNOR database. Finally, molecular docking analyses and cell viability assay were used to identify a potential candidate drug and verify its growth inhibition ability to A431 cell line. Results: Fifty-one common differentially expressed genes were screened and two key modules were identified. Among them, three core genes were extracted, constituting two signalling pathways, both of which belong to the module associated with mitotic spindles and cell division. A pathway involving CDK1, the TPX2-KIF11 complex, and spindle organization was validated in a series of analyses, including analyses for overall survival, genetic alteration, and molecular structure. Molecular docking analyses identified the pyridine 2-carbaldehyde thiosemicarbazone (NSC689534), which interacts with TPX2 and KIF11, as a potential candidate for the treatment of cSCC. Conclusions: NSC689534 might be a candidate drug for cSCC targeting TPX2 and KIF11, which are hub genes in cSCC.

Abstract Background Because of dismal prognosis in gastric cancer, identifying relevant prognostic factors is necessary. Phosphoserine phosphatase (PSPH) exhibits different expression patterns in many cancers and has been reported to affect the prognosis of patients with cancer. In this study, we examined the prognostic role of metabolic gene PSPH in gastric cancer based on the TCGA dataset and our hospital–based cohort cases. Methods We collected and analysed RNA-seq data of Pan-cancer and gastric cancer in the TCGA dataset and PSPH expression data obtained from immunohistochemical analysis of 243 patients with gastric cancer from Sun Yat-sen University cancer center. Further, Kaplan–Meier survival analysis and Cox analysis were used to assess the effect of PSPH on prognosis. The ESTIMATE and Cibersort algorithms were used to elucidate the relationship between PSPH and the abundance of immune cells using the TCGA dataset. Results We observed that PSPH expression displayed considerably high in gastric cancer and it was significantly associated with inferior prognosis (P = 0.043). Surprisingly, there was a significant relationship between lower immune scores and high expression of PSPH (P

The m7G modification has been proven to play an important role in RNA post-transcriptional modification and protein translation. However, the potential role of m7G modification patterns in assessing the prognosis of Skin cutaneous melanoma (SKCM) and tumor microenvironment (TME) has not been well studied. In this study, we investigated and finally identified 21 available m7G-related genes. We used hierarchical clustering (K-means) to classify 743 SKCM patients into three m7G-modified subtypes named m7G/gene cluster-A, B, C. We found that both m7G cluster B and gene cluster B exhibited higher prognosis and higher immune cell infiltration in TME compared to other subtypes. EIF4E3 and IFIT5, two m7G related genes, were both markedly elevated in Cluster B. Then, we constructed an m7G score system utilizing principal component analysis (PCA) in order to evaluate the patients' prognosis. High m7G score subtype was associated with better survival prognosis and active immune response. Overall, this article revealed that m7G modification patterns were involved in the development of the tumor microenvironment. Evaluating patients' m7G modification patterns will enhance our understanding of TME characteristics and help to guide personal treatment in clinics in the future.

AIM: To explore the efficacy of Qiju Dihuang decoction combined with sodium hyaluronate eye drops in the treatment of xerophthalmia after cataract surgery.METHODS: A total of 120 patients with xerophthalmia after cataract surgery admitted to our hospital were selected between January 2018 and January 2020, and randomly divided into control group and observation group, with 60 cases in each group. The control group was treated with sodium hyaluronate eye drops alone, and the observation group was given Qiju Dihuang decoction combined with sodium hyaluronate eye drops, and they were treated for 1mo. The clinical efficacy, Traditional Chinese Medicine(TCM)syndromes scores, tear film break-up time(BUT), Schirmer Ⅰ test(SⅠt), corneal fluorescein staining(FL)and quality of life [25-item National Eye Institute Visual Function Questionnaire(NEI-VFQ-25)]were compared between the two groups.RESULTS:After treatment, the total effective rate of treatment was 93% in observation group and was 75% in control group(P

BackgroundFew studies have investigated the associations of childhood growth trajectories with the prenatal metabolic risks of mothers and their interaction with children’s genetic susceptibility.ObjectiveTo investigate the effects of gestational metabolic syndrome (GMS) risks and children’s polygenic risk scores (PRSs), and their interaction effect on the BMI trajectory and obesity risk of offspring from birth to 6 years of age.MethodsA total of 2,603 mother-child pairs were recruited from the Ma’anshan birth cohort (Anhui Province of China) study. Data on maternal prepregnancy obesity, gestational weight gain (GWG), gestational diabetes mellitus (GDM), and hypertensive disorders of pregnancy (HDP) were used to evaluate maternal GMS risk. In addition, 1,482 cord blood samples were used to genotype 11 candidate single-nucleotide polymorphisms (SNPs) to calculate children’s PRSs. The latent class growth model using the longitudinal BMI-for-age z scores (BMIz) was applied to validly capture the BMIz growth trajectory.ResultsMaternal GMS status was associated with higher BMIz scores and with an increased risk of overweight/obesity. Positive relationships were revealed between PRS and the risk of overweight/obesity among girls. Additionally, maternal GMS significantly interacted with the child’s PRS on BMIz scores and the risk of overweight/obesity among girls. Hierarchical BMI trajectory graphs by different exposure groups showed consistent findings, and both boys’ and girls’ BMIz trajectories were divided into three groups. Among girls, the higher the GMS risk or PRS they had, the higher the probability of being in the high BMIz trajectory group.ConclusionsMaternal GMS status increased BMIz scores and the risk of obesity in both boys and girls and elevated the child’s BMI trajectory from birth to 6 years of age among girls. PRSs were significantly associated with children’s BMI trajectory and the risk of obesity and modified the associations between maternal GMS status and obesity biomarkers only among girls. Thus, regarding childhood obesity, steps should be taken to decrease maternal metabolic risks before and during pregnancy, and sex discrepancies should be noted to identify high-risk populations after birth to hierarchically manage them.

AIM: To analyze the influence of bandage contact lens on corneal refractive status and postoperative complications in patients with pterygium. METHODS: Totally 116 patients with pterygium treated in the hospital between January 2018 and December 2019 were recruited in the study. They were divided into control group and observation group by random number table method, 58 cases in each group. The control group received extended pterygium resection and autologous corneal limbal stem cell transplantation. On this basis, the observation group was treated with bandage contact lens. The best corrected visual acuity(BCVA), surface asymmetry index(SAI)of corneal topography, surface regularity index(SRI), corneal refractive power and postoperative complications in the two groups were compared. RESULTS: Compared with preoperation, the BCVA of the two groups was significantly higher 1mo and 3mo after operation(P0.05). Corneal horizontal and vertical curvature of the two groups were significantly higher, while corneal astigmatism was significantly lower at 1mo and 3mo after surgery. Meanwhile, the observation group had significantly lower corneal astigmatism than the control group(P

Abstract Objective Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the two most common hyperglycemic emergencies (HEs) associated with diabetes mellitus. Individuals with HEs can present with combined features of DKA and HHS. The objective of this study is to assess the clinical characteristics, therapeutic outcomes, and associated predisposing factors of type 2 diabetic patients with isolated or combined HEs in China. Methods We performed a retrospective analysis of 158 patients with type 2 diabetes (T2DM), complicated with DKA, HHS, or DKA combined with HHS (DKA-HHS) in Shanghai Tongji Hospital, China from 2010 to 2015. Admission clinical features, therapeutic approaches and treatment outcomes of those patients were extracted and analyzed. Results Of the 158 patients with T2DM, 65 (41.1%) patients were DKA, 74 (46.8%) were HHS, and 19 (12.0%) were DKA-HHS. The most common precipitants were infections (111, 70.3%), newly diagnosed diabetes (28,17.7%) and non-compliance to medications (9, 5.7%). DKA patients were divided into mild, moderate and severe group, based on arterial blood gas. Spearman correlation analysis revealed that C-reaction protein (CRP) was positively correlated with severity of DKA, whereas age and fasting C peptide were inversely correlated with severity of DKA (P

Abstract In this study, durable slippery colloidal coatings are created through the infiltration of particulate films with bilayer lubricant; the coatings exhibit remarkable surface‐protective performance, including anticorrosion, antifouling, self‐healing, anti‐icing, and self‐cleaning properties. Materials with low surface energy, namely polytetrafluoroethylene or polydimethylsiloxane, are used to form micelle dispersions, with particulate films then obtained through spray coating. In particular, the thermally driven viscous surfactants can serve as a bottom adhesive primer after thermal treatment, which significantly improve durability. After lubricant infusion as a top protective layer, bilayer lubricant‐infused slippery coatings are obtained without a complex hole‐making process being required. The anticorrosion and antifouling performance of colloid coatings infused with various functional lubricants—ionic liquid, silicone oil, and perfluoropolyether oils—is investigated. This study is the first to create bilayer lubricant‐infused colloid‐based surface systems (i.e., primer and protective lubricants) as protective coatings. The coatings can be employed in various applications, such as fuel transport, self‐cleaning windows, anticorrosion protection, nontoxic coatings for medical devices, and optical instruments.

Objective: To evaluate virulence of itraconazole-resistant Sporothrix globosa and its sensitivity to itraconazole in Galleria mellonella. Methods: Itraconazole-resistant strain and itraconazole-sensitive strain of S. globosa were used to infect the Galleria mellonella larvae. Change in appearance, body feedback and survival of the larva were observed. Itraconazole was injected into the infected larvae at a dose of 20 mg/kg and 40 mg/kg, respectively. The survival and fungal burden of the larva were observed. Results: At the end of observation, there was no statistical difference in the survival curve between the resistant-strain group and sensitive-strain group (χ2=2.37, P=0.124). After injecting itraconazole at 40 mg/kg, the survival rates of itraconazole-resistant strain and itraconazole-sensitive strain increased by 40% and 60%, respectively, and there was no statistical difference between them (χ2=1.20, P=0.466).The colony count of CBS120340 was significantly lower than that of SUMS0381(t=-18.64, P

Few studies have investigated the association of gestational exposure to phthalate with metabolic risk and have reached inconsistent conclusions. Based on the Ma’anshan Birth Cohort, 3273 women were included in the present study. All participants provided up to three urine samples for 7 phthalate metabolite measurements. The hazard index (HI) was used to evaluate the cumulative risk of multiple phthalate coexposures. The outcomes of interest included hypertensive disorders of pregnancy (HDOP), gestational diabetes mellitus (GDM), and gestational weight gain (GWG). The incidences of HDOP, GDM, and excessive GWG were 5.93%, 13.09%, and 28.95%, respectively. Exposure to a single phthalate metabolite or a specific diester during the first trimester of pregnancy elevated blood pressure (BP) and fasting plasma glucose (FPG) in the third trimester and body weight gain throughout pregnancy. However, inverse relationships were revealed for some phthalate metabolites, which were inconsistent with the results of their diesters. The HI value during the first trimester was positively associated with subsequent BP, FPG, and GWG. In addition, HI during the first trimester increased the risks of GDM [odds ratio (OR) = 1.34, 95% confidence intervals (CIs) = 1.02–1.75)] and excessive GWG (OR = 1.76, 95% CIs = 1.41–2.19) in a linear manner thereafter. Notably, phthalates might directly increase maternal blood glucose and pressure, and these changes were secondary effects of the obesiogenic effects of certain phthalates. In conclusion, exposure to single and multiple phthalates during the first trimester of pregnancy increased the risks of maternal metabolic syndrome components. However, the conflicting findings between phthalates and their metabolites need to be interpreted carefully.

Abstract It has been extensively reported that long noncoding RNAs (lncRNAs) were closely associated with multiple malignancies. The aim of our study was to investigate the effects and mechanism of lncRNA POU6F2-AS1 in lung adenocarcinoma (LADC).The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets provided us the information of LADC clinical samples. High-regulation of POU6F2-AS1 was presented in LADC tissues compared with adjacent normal tissues, which was correlated with poor outcome of LADC patients. Functional experiments in Calu-3 and NCI-H460 cells showed that POU6F2-AS1 significantly promoted LADC cell proliferation, colony formation, invasion and migration. Moreover, through online prediction, luciferase reporter assay and Pearson’s correlation analysis, we found that POU6F2-AS1 may act as a competing endogenous RNA (ceRNA) of miR-34c-5p and facilitated the expression of potassium voltage-gated channel subfamily J member 4 (KCNJ4). The promoting effect of cell aggressiveness induced by POU6F2-AS1 was enhanced by KCNJ4, whilst was abrogated due to the overexpression of miR-34c-5p. Collectively, POU6F2-AS1 might function as a ceRNA through sponging miR-34c-5p to high-regulate KCNJ4 in LADC, which indicates that POU6F2-AS1 might be a promising therapeutic target with significant prognostic value for LADC treatment.

Background: Phthalates are a group of heavily produced endocrine disruptors that are widely used in personal care products, food packaging, building materials, and medical device. Few epidemiological studies have examined the effect of repeated prenatal exposure to multiple phthalates on preschooler cognitive development. Objectives: This study aimed to examine the association between prenatal phthalate exposure measured at multiple time points and the intelligent quotient (IQ) scores of preschoolers, and to further identify the critical windows and specific intelligence domains in which phthalate exposure would affect preschooler cognitive development. Methods: The current study was based on the Ma’anshan Birth Cohort (MABC) study. Seven phthalate metabolites were measured in 2128 maternal urine samples collected during the first, second, and third trimesters of pregnancy. The IQ score of preschool-aged children were assessed with the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth edition (WPPSI-Ⅳ CN). Linear mixed models (LMMs) were used to assess the longitudinal effects of repeated prenatal phthalate exposure on children’s IQ score. Multiple linear regression models were fitted to determine whether critical window phthalate exposure would affect cognitive development of children. Results: Overall, the repeated measures analysis indicated that the verbal comprehension index (VCI), visual space index (VSI) and full-scale intelligence quotient (FSIQ) decreased by 0.30 (95% CI: −0.60, 0; p = 0.05), 0.32 (95% CI: −0.62, −0.01; p = 0.04), and 0.31 (95% CI:-0.57, −0.04; p = 0.02) points, respectively, with each ln-transformed increase in the metabolite concentration of MBP. The fluid reasoning index (FRI) and processing speed index (PSI) increased by 0.30 (95% CI: 0.07, 0.54; p = 0.01) and 0.28 (95% CI: 0.06, 0.51; p = 0.01) points, respectively, with each ln-concentration increase in MEP. Trimester-specific regression models stratified by the sample collection time during pregnancy generated consistent results. In the first trimester, each ln-transformed MBP increase was associated with reductions in VCI, VSI and FSIQ of 0.56 (95% CI:-1.09, −0.02; p = 0.04), 0.60 (95% CI:-1.15, −0.05; p = 0.03) and 0.49 (95% CI:-0.97, −0.01; p = 0.04) points, respectively. In the third trimester, we observed that only MBzP exposure was associated with an increase in VCI (β: 0.48, 95% CI: 0.03, 0.92; p = 0.04). The gender-stratified analyses revealed that boys drove these associations. Conclusions: Our results suggest that prenatal phthalate exposure impairs the cognitive development of preschoolers. The first trimester of pregnancy might be the most vulnerable period in terms of neurotoxicitydue to phthalate exposure. These findings warrant further confirmation.

Objective: To predict biological characterisics of 4-HppD, encoded by 4Hppd in Sporothrix schenckii. Methods: Mutiple bioinformatics online tools were used to analyse the sequence. Results: Ss.4HppD, located in mitochodria, was formed by 477 amino acids and its theoretical molecular weight is 52.0 kD. The isoelectric point was about 5.98, with a long half life. The dominant secondary structures in Ss.4HppD were random coil and alpha helix. Besides, Ss.4HppD had a similar tertiary structure with its homologue proteins, a glyoxalase motif at the carboxy end and multiple phosphorylation sites. Conclusion: Ss.4HppD was predicted to located in mitochondria, with a glyoxalase motif and various modification sites, which would facilitate the further researches in the protein including protein expression, function mechanism and inhibitior development.

The evolution of microstructure and mechanical properties of A356 aluminum alloy subjected to hot spinning process has been investigated. The results indicated that the deformation process homogenized microstructure and improved mechanical properties of the A356 aluminum alloy. During the hot spinning process, eutectic Si particles and Fe-rich phases were fragmented, and porosities were eliminated. In addition, recrystallization of Al matrix and precipitation of AlSiTi phases occurred. The mechanical property testing results indicated that there was a significant increase of ductility and a decrease of average microhardness in deformed alloy over die-cast alloy. This is attributed to uniform distribution of finer spherical eutectic Si particles, the elimination of casting defects and to the recrystallized finer grain structure.

Human adenovirus type 55 (HAdV-B55) represents a re-emerging human pathogen, and this adenovirus has been reported to cause outbreaks of acute respiratory diseases among military trainees and in school populations around the world. HAdV-B55 has been revealed to have evolved from homologous recombination between human adenovirus type 14 (HAdV-B14) and type 11 (HAdV-B11), but it presents different clinical manifestations from parental virus HAdV-B11. In the present paper, we report the distinct biological features of HAdV-B55 in comparison with the parental viruses HAdV-B11 and HAdV-B14 in cell cultures. The results showed that HAdV-B55 replicated well in various cells, similar to HAdV-B11 and HAdV-B14, but that its processing had a slower and milder cytopathic effect in the early stages of infection. Viral fitness analysis showed that HAdV-B55 exhibited higher levels of replication in respiratory cells than did either of its parents. Cytotoxicity and apoptosis analyses in A549 cells indicated that HAdV-B55 was less cytotoxic than HAdV-B11 and HAdV-B14 were and induced milder apoptosis. Finally, thermal sensitivity analysis revealed that HAdV-B55 exhibited lower thermostability than did either HAdV-B11 or HAdV-B14, which may limit the transmission of HAdV-B55 in humans. Together, the findings described here expand current knowledge about this re-emerging recombinant HAdV, shedding light on the pathogenesis of HAdV-B55.

Human enterovirus 71 (HEV71) has emerged as the leading cause of viral encephalitis in children in most Asian countries. The roles of host miRNAs in the neurological pathogenesis of HEV71 infection remain unknown. In the present study, comprehensive miRNA expression profiling in HEV71-infected human neuroblastoma SH-SY5Y cells was performed using the Affymetrix Gene Chip microarray assay and was validated using real-time RT-PCR. Among the 69 differentially expressed miRNAs, miR-1246 was specifically induced by HEV71 infection in human neuroblastoma cells, but inhibition of miR-1246 failed to affect HEV71 replication. Parallel mRNA and microRNA profiling based on the 35 K Human Genome Array identified 182 differentially regulated genes. Target prediction of miR-1246 and network modeling revealed 14 potential target genes involved in cell death and cell signaling. Finally, a combined analysis of the results from mRNA profiling and miR-1246 target predication led to the identification of disc-large homolog 3 (DLG3), which is associated with neurological disorders, for further validation. Sequence alignment and luciferase reporter assay showed that miR-1246 directly bound with the 3'-UTR of DLG3 gene. Down-regulation of miR-1246 induced significant changes in DLG3 expression levels in HEV71-infected SHSY5Y cells. Together, these results suggested that miR-1246 might play a role in neurological pathogenesis of HEV71 by regulating DLG3 gene in infected cells. These findings provide new information on the miRNA and mRNA profiles of HEV71-infected neuroblastoma cells. The biological significance of miR-1246 and DLG3 during the course of HEV71 infection deserves further investigation.

Human enterovirus type 71 (EV71) is the major pathogen of hand-foot-and-mouth disease (HFMD) and has been associated with severe neurological disease and even death in infants and young children. The pathogenesis of EV71 infection in the human central nervous system remains unclear. In this study, human whole genome microarray was employed to perform transcriptome profiling in SH-SY5Y human neuroblastoma cells infected with EV71. The results indicated that EV71 infection lead to altered expression of 161 human mRNAs, including 74 up-regulated genes and 87 down-regulated genes. Bioinformatics analysis indicated the possible roles of the differentially regulated mRNAs in selected pathways, including cell cycle/proliferation, apoptosis, and cytokine/chemokine responses. Finally, the microarray results were validated using real-time RT-PCR with high identity. Overall, our results provided fundamental information regarding the host response to EV71 infection in human neuroblastoma cells, and this finding will help explain the pathogenesis of EV71 infection and virus-host interaction.

Microwave thermal shock is an optimized means of crushing rocks in engineering, in order to investigate the effect of microwave thermal shock on granite, this paper adopts microwave irradiation and SEM experiments to investigate the mechanical behavior and microstructural evolution law of granite, and the main conclusions are: With the increase of the duration of thermal shock, granite exhibits the law of linear increase, and the peak strength and elastic modulus show the trend of rising first and then decreasing; After thermal shock the acoustic emission signal of granite is linearly rising, while the internal shear cracks expand to form larger transgranular cracks, the results of the study have great significance for the future development of traditional mining technology. [ABSTRACT FROM AUTHOR]