Cardiac magnetic resonance feature tracking myocardial strain analysis in suspected acute myocarditis: diagnostic value and association with severity of myocardial injury.

BACKGROUND: Albeit that cardiac magnetic resonance feature tracking (CMR-FT) has enabled quantitative assessment of global myocardial strain in the diagnosis of suspected acute myocarditis, the cardiac segmental dysfunction remains understudied. The aim of the present study was using CMR-FT to assess the global and segmental dysfunction of the myocardium for diagnosis of suspected acute myocarditis. METHODS: Forty-seven patients with suspected acute myocarditis (divided into impaired and preserved left ventricular ejection fraction [LVEF] groups) and 39 healthy controls (HCs) were studied. A total of 752 segments were divided into three subgroups, including segments with non-involvement (SNi), segments with edema (SE), and segments with both edema and late gadolinium enhancement (SE+LGE). 272 healthy segments served as the control group (SHCs). RESULTS: Compared with HCs, patients with preserved LVEF showed impaired global circumferential strain (GCS) and global longitudinal strain (GLS). Segmental strain analysis showed that the peak radial strain (PRS), peak circumferential strain (PCS), and peak longitudinal strain (PLS) values significantly reduced in SE+LGE compared with SHCs, SNi, SE. PCS significantly reduced in SNi (-15.3 ± 5.8% vs. -20.3 ± 6.4%, p < 0.001) and SE (-15.2 ± 5.6% vs. -20.3 ± 6.4%, p < 0.001), compared with SHCs. The area under the curve (AUC) values of GLS (0.723) and GCS (0.710) were higher than that of global peak radial strain (0.657) in the diagnosis of acute myocarditis, but the difference was not statistically significant. Adding the Lake Louise Criteria to the model resulted in a further increase in diagnostic performance. CONCLUSIONS: Global and segmental myocardial strain were impaired in patients with suspected acute myocarditis, even in the edema or relatively non-involved regions. CMR-FT may serve as an incremental tool for assessment of cardiac dysfunction and provide important additional imaging-evidence for distinguishing the different severity of myocardial injury in myocarditis.

Epidemiological and CBCT characterizations of odontomas: A retrospective study of 87,590 subjects.

OBJECTIVES: This study aimed to assess the epidemiological and three-dimensional (3D) radiological characterizations of odontomas, as well as the spatial relationship between odontomas and gubernaculum tracts (GT). MATERIALS AND METHODS: We retrieved the cone-beam computed tomography (CBCT) data of 87,590 patients. Dentition, location, type, diameter of the odontomas, width of the dental follicle (DF), the spatial relationship between the odontoma and GT, and the influence on adjacent teeth were evaluated. RESULTS: Significant differences were found in age, dentition, location, Max/Min diameter, width of DF, impaction, retention, and root bending of adjacent teeth among different spatial relationships between the odontoma and GT (all p < 0.05), as well as in age, type and size, absence, impaction, malposition, and retention of adjacent teeth among different locations of odontomas (all p < 0.05). Compared to the odontomas without impaction, those with impaction had larger diameter (p < 0.05 in all directions). This statistically significant association was consistent for odontomas with malposition, while no similar result was observed in the maximum diameter. CONCLUSION: Our findings provide the preliminary data for clinicians to comprehensively understand the incidence, radiographic characterizations and symptoms of odontoma in Chinese population.

A Review of Microsurgical Resection of Recurrent Laryngeal Neurilemmoma Under Nerve Monitoring.

BACKGROUND: Laryngeal neurilemmoma, especially recurrent laryngeal neurilemmoma, is a rare neural sheath tumor in head and neck. The most common symptom of laryngeal neurilemmoma is hoarseness or dysphonia, followed by dysphagia, dyspnea, and foreign body sensation. At present, surgical resection is the most effective treatment for this kind of tumor, thus making how to remove it become the most concerned problem of surgeons. CASE PRESENTATION: On February 18, 2021, a 64-year-old male presented to our clinic with recurrent sore throat and intermittent hoarseness for 3 years. The results of electronic laryngoscope and magnetic resonance imaging showed a 25×10×21 mm well-defined tumor in the left pyriform sinus without laryngeal cartilage destruction and enlarged lymph nodes. After the initial diagnosis of recurrent laryngeal neurilemmoma, to preserve the continuity of recurrent laryngeal nerve as much as possible, the authors determine to perform anatomical resection of recurrent laryngeal neurilemmoma with operating microscope under the monitoring of recurrent laryngeal nerve function. Finally, the patient recovered completely from hoarseness during postoperative follow-up. CONCLUSION: A complete diagnosis and treatment process of recurrent laryngeal neurilemmoma was presented by the case. Particularly, it shows the application of recurrent laryngeal nerve monitoring in the operation helps to protect the continuity of the recurrent laryngeal nerve, which lays a anatomical bases for the follow-up nerve repair.

A multi-method evaluation of the effects of Inflammatory cytokines (IL-1ß, IFN-γ, TNF-α) on pancreatic ß-cells.

We aimed to explore the effects of Inflammatory cytokines (IL-1ß, IFN-γ, TNF-α) on pancreatic ß-cells. CCK-8 assay showed that the cell viability decreased after 24 hr treatment of TNF-α, 48 hr of IFN-γ, and 84 hr of IL-1ß. EdU assay illustrated that after 24 hr treatment, there were significantly reduced EdU-labeled red fluorescence cells in TNF-α group while not in IFN-γ and IL-1ß groups. Flow Cytometry results displayed that TNF-α and IFN-γ groups increased apoptosis while IL-1ß group did not. Cell apoptosis results found that there was an increase in the S-phase population of IL-1ß and TNF-α groups, however, there was no significant difference in cell cycle between IFN-γ group and the control. TEM images showed that there were reduction in the number of granules and mitochondria in IL-1ß and IFN-γ groups, in particular paucity of insulin granules and mitochondria in TNF-α group. Radioimmunoassay results presented that TNF-α inhibited glucose-induced insulin secretion, while there were no significant changes in IL-1ß and IFN-γ groups when compared with the control. Metabolomic analysis found amino acid metabolism and Krebs cycle were the most robust altered metabolism pathways after inflammatory cytokines treatments. Overall, the altered amino acid metabolism and Krebs cycle metabolism might be important mechanisms of TNF-α induced mouse pancreatic ß-cells dysfuction.

GM13133 is a negative regulator in mouse white adipocytes differentiation and drives the characteristics of brown adipocytes.

Obesity is tightly associated with the disturbance of white adipose tissue storing excess energy. Thermogenic adipocytes (brown and beige) exert a critical role of oxidizing nutrients at the high rates through non-shivering thermogenesis. The recruitment of brown characteristics in white adipocytes, termed browning, has been considered as a promising strategy for treating obesity and associated metabolic complications. Recently, long noncoding RNAs play a crucial role in regulating tissue development and participating in disease pathogenesis, yet their effects on the conversion of white into brown-like adipocytes and thermogenic function were not totally understood. Here, we identified a mouse brown adipose specific expressed lncRNA, termed GM13133. Moreover, a considerable amount of GM13133 is expressed in adipocytes and actively modulated by cold, ß3 -adrenergic agonist and cAMP stimuli, implying a potential role in the conversion from white to brown adipocytes. Overexpression of GM13133 did not affect the proliferation of mouse white pre-adipocytes, but inhibited white adipocyte differentiation by decreasing lipid accumulation. The forced expression of GM13133 also significantly drove the conversion of white into brown-like adipocytes with the enhanced mitochondrial biogenesis and the induced expression of brown adipocytes specific markers. A global mRNA analysis further indicated the possible regulatory role of cAMP signaling pathway in GM13133 mediated white-to-brown adipocytes conversion. Our results identified a lncRNA-mediated modulation in primary mouse white adipocyte differentiation and indicate the functional significance of GM13133 in promoting browning of white adipocytes and maintenance of thermogenesis, further providing a potential strategy to treating obesity.

High folate intake contributes to the risk of large for gestational age birth and obesity in male offspring.

Folate supplementation is recommended before and during early pregnancy to prevent neural tube defects, but the effect of red blood cell (RBC) folate on large for gestational age (LGA) is still unknown. We performed a nested case-control study including 542 LGA cases and 1,084 appropriate for gestational age (AGA) controls to examine the association of RBC folate concentrations with risk of LGA. Then, male offspring of dams fed basic folic acid (2 mg/kg, control) or 10-fold folic acid (20 mg/kg, HFol) diet before and during pregnancy were used to explore the effect of high folate intake on birth weight and long-term effects. We observed higher RBC folate concentrations in the cases compared to controls (p = 0.039). After adjustment for maternal age, BMI at enrollment, gestational weeks at enrollment, gestational weeks at delivery and infant gender, higher RBC folate levels were significantly associated with increased risk of LGA (Ptrend = 0.003). Interestingly, male offspring of HFol dams showed the higher birth weight, elevated levels of post loading blood glucose at 9 and 13 weeks post-weaning and increased triglyceride (TG) and total cholesterol (TC) levels at 17 weeks post-weaning. Furthermore, we observed that high folate intake increased the proliferation and differentiation of adipose cells. Our results suggest that maternal high folate intake confers the risk of LGA birth and accelerates the development of obesity in male offspring.

Identification and characterization of metformin on peptidomic profiling in human visceral adipocytes.

To gain insight into the effect of metformin on losing weight from peptidomic perspective and to screen potential active peptides for reducing fat lipid deposition. After determining the proper concentration of metformin on human primary visceral adipocytes, we constructed a comparative peptidomic profiling between control and metformin treatment group (n = 3) using a stable isobaric labeling strategy involving tandem mass tag reagents, followed by liquid chromatography tandem mass spectrometry. We identified and quantified 3065 non-redundant peptides, 304 of which were differentially expressed after metformin treatment, 206 peptides were up regulated and 98 peptides were down regulated significantly. Gene ontology (GO) enrichment and pathway analysis were performed to study differentially peptides though their precursor proteins. We concluded three peptides located within the functional domains of their precursor proteins could be candidate bioactive peptides for obesity. On one hand, these results confirmed the versatile effects of metformin on adipocyte and advance our current understanding of metformin, on the other hand, these identified peptides might play putative roles in treatment of obesity.

Long Non-Coding RNA Expression Profiles for the Characterization of Different Bladder Cancer Grade.

BACKGROUND/AIMS: Bladder cancer (BC) is one of the most frequent urologic tumors worldwide. However, long non-coding RNA(lncRNA) expression profiles in BC progression remain unclear. This study aimed to explore lncRNA expression profiles in different grades of bladder cancer and normal urothelium tissues. METHODS: We performed high-throughput sequencing in BC tissues of different grade and obtained the expression profiles of its lncRNAs. Then, aberrantly expressed lncRNAs were validated by quantitative reverse transcription polymerase chain reaction (RT-PCR). Gene Ontology (GO) and pathway analyses were used to investigate the potential function of these lncRNAs. Co-expresson network was constructed to explore the relationship between lncRNAs and target mRNAs. RESULTS: We identified 252 aberrantly expressed lncRNAs in high-grade BC while compared to low-grade BC, and 269 lncRNAs in high-grade BC while compared to normal urothelium. Notably, we found 33 overlapped lncRNAs. Subsequently, 7 lncRNAs were selected from the overlapped part and confirmed by RT-PCR. GO and pathway analyses showed that these dysregulated lncRNAs participated in cell migration, cell adhesion, as well as Ras signaling pathway. Co-expression network and The Cancer Genome Atlas (TCGA) data showed LUCAT1 and CCNB1 had positive relationship in regulating the progress of bladder cancer. CONCLUSION: Our findings revealed the significant role of lncRNAs in the development process of bladder cancer.

Association of Thyroid Function With the Estimated Glomerular Filtration Rate in a Large Chinese Euthyroid Population.

BACKGROUND/AIMS: We aimed to explore whether thyroid function within a normal range is associated with the estimated glomerular filtration rate (eGFR) and the incidence of chronic kidney disease (CKD) in a large Chinese population. METHODS: We conducted a cross-sectional study that included 10,859 euthyroid individuals who underwent an annual regular health checkup in Jiangsu Province Official Hospital between August 2012 and August 2013. We measured the thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels using a Roche modular analytics E170 and then calculated the eGFR using the Chinese modified Modification of Diet in Renal Disease (CMDRD) equation. RESULTS: In multiple linear regression models, TSH was negatively associated with eGFR after adjusting for confounding factors (ß = -0.072, P = 1.994×10-22). The significance remained in both males and females. No significant association was observed between FT4 and eGFR. In the logistic regression model, we did not observe significant associations of TSH or FT3 with CKD. Participants in the highest quartile of FT4 versus the lowest quartile (reference) had an increased risk of CKD (OR = 1.763, P = 0.012). The risk of CKD was more pronounced in females with the highest quartile of FT4 (OR = 2.424, P = 0.029). CONCLUSION: Our findings suggest that TSH is associated with eGFR in euthyroid individuals and that higher FT4 is associated with an increased risk of CKD. More cohort studies are warranted to confirm whether the association is causal.

Metabolome-wide association study identified the association between a circulating polyunsaturated fatty acids variant rs174548 and lung cancer.

Quantitative trait loci (QTLs) are widely used as instruments to infer causal risk factors of diseases based on the idea of mendelian randomization. Plasma metabolites can serve as risk factors of cancer, and the heritability of many circulating metabolites was high. We conducted a metabolome-wide association study (MWAS) to systematically investigate the effects of genetic variants on metabolites and lung cancer based on published genome-wide association study (GWASs) and metabolic-QTL (mQTL) study. Then we confirmed the results by subsequent genetic and metabolic validations and inferred the causal relationship between identified metabolites and lung cancer through genetic variant(s). We firstly identified six polyunsaturated fatty acids (PUFAs) represented by rs174548-linked haplotype were significantly associated with lung cancer risk in a Chinese GWAS (2311 cases and 3077 controls). Rs174548 was further confirmed to be associated with lung cancer in 13 821 Europeans and 18 471 Asians (ORmeta = 0.87, Pmeta = 1.76 × 10-15) and the effect was much stronger in females (Pinteraction = 6.00 × 10-4). We next validated rs174548-plasma PUFA association in 253 Chinese subjects (ß = -0.57, P = 1.68 × 10-3). Rs174548 was also found associated with FADS1 (the major fatty acid desaturase of identified PUFAs) expression in liver tissues. Taken together, we found that rs174548 was associated with both PUFAs and lung cancer. Because rs174548 was the only mQTL variant of PUFAs reported by previous GWASs and explained a large proportion of heritability, we proposed that plasma PUFAs could be causally associated with lung cancer based on the idea of mendelian randomization. These findings provide a diet-related risk factor and may have important implications for prevention on lung cancer.

A polymorphism in miR-1262 regulatory region confers the risk of lung cancer in Chinese population.

It has been proposed that the majority of disease-associated loci identified by genome-wide association studies (GWAS) are enriched in non-coding regions, such as the promoter, enhancer or non-coding RNA genes. Thus, we performed a two-stage case-control study to systematically evaluate the association of genetic variants in miRNA regulatory regions (promoter and enhancer) with lung cancer risk in 7,763 subjects (discovery stage: 2,331 cases and 3,077 controls; validation stage: 1,065 cases and 1,290 controls). As a result, we identified that rs12740674 (C > T) in miR-1262 enhancer was significantly associated with the increased risk of lung cancer (additive model in discovery stage: adjusted OR = 1.31, 95%CI = 1.13-1.53, p = 3.846 × 10-4 in Nanjing GWAS; adjusted OR = 1.20, 95%CI = 1.00-1.44, p = 0.041 in Beijing GWAS; validation stage: adjusted OR = 1.20, 95%CI = 1.03-1.41, p = 0.024). In meta-analysis, the p value for the association between rs12740674 and lung cancer risk reached 6.204 × 10-6 (adjusted OR = 1.24, 95%CI = 1.13-1.36). Using 3DSNP database, The Cancer Genome Atlas (TCGA) data and functional assays, we observed that the risk T allele of rs12740674 reduced the expression level of miR-1262 in lung tissue through chromosomal looping, and overexpression of miR-1262 inhibited lung cancer cell proliferation probably through targeting the expression levels of ULK1 and RAB3D. Our findings confirmed the important role that genetic variants of noncoding sequence play in lung cancer susceptibility and indicated that rs12740674 in miR-1262 may be biologically relevant to lung carcinogenesis.

A transcribed ultraconserved noncoding RNA, uc.417, serves as a negative regulator of brown adipose tissue thermogenesis.

Brown adipose tissue (BAT) oxidizes fatty acids for thermogenesis and could therefore be considered as part of a new strategy in combating obesity and associated metabolic diseases. It is well established that aging is accompanied by a decline of brown adipocyte regenerative capacity. How aging contributes to this loss is poorly understood. Here, we identify a long noncoding RNA, uc.417, which is transcribed from an ultraconserved region in rodents. Expression of uc.417 increases with age. Ectopic expression of uc.417 impairs adipogenesis and the thermogenic program in brown adipocytes. However, uc.417 is not required for brown fat function. In vivo, uc.417 attenuates the cold-induced thermogenic program in mouse BAT. Moreover, we find that uc.417 moderately inhibits phosphorylation of p38MAPK without affecting the total protein level of p38MAPK. The p38MAPK pathway is essential for activating BAT to stimulate uncoupling protein 1 gene expression. The data point to uc.417 as being an important factor in an age-dependent loss of function of brown adipose tissue.-Cui, X., You, L., Li, Y., Zhu, L., Zhang, F., Xie, K., Cao, Y., Ji, C., Guo, X. A transcribed ultraconserved noncoding RNA, uc.417, serves as a negative regulator of brown adipose tissue thermogenesis.

Role of ATG10 expression quantitative trait loci in non-small cell lung cancer survival.

The aim of this article was to evaluate whether genetic variants in autophagy-related genes affect the overall survival (OS) of non-small cell lung cancer (NSCLC) patients. We analyzed 14 single nucleotide polymorphisms (SNPs) in core autophagy-related genes for OS in 1,001 NSCLC patients. Three promising SNPs in ATG10 were subsequently annotated by the expression quantitative trait loci (eQTL) and methylation quantitative trait loci (meQTL) analyses based on Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. We observed that the variants of rs10514231, rs1864182 and rs1864183 were associated with poor lung cancer survival (HR = 1.33, 95% CI = 1.07-1.65; HR = 1.43, 95% CI = 1.13-1.81; HR = 1.38, 95% CI = 1.14-1.68, respectively) and positively correlated with ATG10 expression (all p < 0.05) from GTEx and TCGA datasets. The elevated expression of ATG10 may predict shorter survival time in lung cancer patients in TCGA dataset (HR = 2.10, 95% CI = 1.33-3.29). Moreover, the variants of rs10514231 and rs1864182 were associated with the increased methylation levels of cg17942617 (meQTL), which in turn contributed to the elevated ATG10 expression and decreased survival time. Further functional assays revealed that ATG10 facilitated lung cancer cell proliferation and migration. Our findings suggest that eQTL/meQTL variations of ATG10 could influence lung cancer survival through regulating ATG10 expression.

The Long Non-Coding RNA ENST00000537266 and ENST00000426615 Influence Papillary Thyroid Cancer Cell Proliferation and Motility.

BACKGROUND/AIMS: Papillary thyroid cancer (PTC) is the most common histotype of Thyroid cancer (TC). Here, we detected the differentially expressed lncRNAs in tumor tissues and non-tumor tissues of PTC patients by lncRNA microarrays, and explored the function and molecular mechanisms of lncRNAs in the pathogenesis of PTC using a PTC cell line. METHODS: CCK-8 assay, colony formation assay and EdU assay were used to detect the cell viability. Flow Cytometry was used to detect the cell cycle and apoptosis. Transwell and scratch assay were used to detect the cell motility. RESULTS: CCK-8 assay, colony formation assay and EdU assay revealed that lncRNAs (ENST00000537266 and ENST00000426615) could inhibit cell proliferation. Cell cycle analysis showed that cell proportion was statistically significant increased in G1 phase and decreased in S phase and G2 phase in Si-266 transfected TPC-1 cells. In addition, a noteworthy increase of cell proportion in G1 phase accompanied by a decrease in S phase and unchanged G2 phase in Si-615 transfected TPC-1 cells were also observed. Meanwhile, transwell and scratch assay showed that ENST00000426615 could inhibit the cell motility while ENST00000537266 could not. CONCLUSION: Our results showed that lncRNAs (ENST00000426615 and ENST00000537266) might be important regulators of PTC cell proliferation and motility, which might provide new insight into the understanding of PTC pathogenesis.

A genetic variant in microRNA-122 regulatory region confers risk for chronic hepatitis B virus infection and hepatocellular carcinoma in Han Chinese.

miR-122 plays a vital role in the development of chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). Based on data from the Encyclopedia of DNA Elements (ENCODE), two single nucleotide polymorphisms (SNPs), rs4309483 and rs4503880, were identified in the upstream regulatory region of miR-122. A case-control study consisting of 1,300 HBV-positive HCC cases, 1,344 HBV carriers, and 1,344 persons who cleared HBV naturally was carried out to test the association between the two SNPs and the risk for chronic HBV infection and HCC. The CA/AA genotypes of rs4309483 were associated with significantly increased risk for HCC [adjusted odds ratio (OR) = 1.21, 95% confidence intervals (CIs) = 1.02-1.43, P = 0.025] compared with HBV carriers, but decreased risk for chronic HBV infection (adjusted OR = 0.82, 95% CIs = 0.70-0.97, P = 0.017) compared with persons who cleared HBV naturally. The genotype-expression correlation between rs4309483 and the expression of primary or mature miR-122 expression was investigated in 29 pairs of HBV positive HCC and noncancerous liver tissues. In noncancerous liver tissues, subjects carrying the CA genotype exhibited significantly lower expression level of pri-miR-122 than those carrying the CC genotype. In addition, positive or inverse correlation between the expression levels of pri-miR-122 and mature miR-122 were observed in HCC tissues or noncancerous tissues, respectively. These findings indicate that the C to A base change of rs4309483 may alter the expression of miR-122, thus providing protective effect from chronic HBV infection but an increased risk for HCC in HBV carriers.

Prognostic significance of serum beta-2 microglobulin in patients with non-Hodgkin lymphoma.

BACKGROUND AND OBJECTIVE: Elevated serum beta-2 microglobulin (ß2-M) has previously been reported in non-Hodgkin lymphoma (NHL) patients. This study examined the association between serum ß2-M and the prognosis of NHL and analyzed its predictive value. METHOD: A total of 287 NHL patients from Taiyuan, Shanxi, China, participated in a prospective cohort study between 2008 and 2011. Overall survival (OS) was compared between NHL patients with high and normal ß2-M levels using the log-rank test. Three standard Cox regression models including the International Prognostic Index (IPI) score, ß2-M or IPI score+ß2-M as independent variables were constructed. The time-dependent receiver operating characteristic curves method and C index were used to examine the tendency of the models' predictive accuracy over time. RESULTS: NHL patients with elevated ß2-M values had worse OS (p<0.001) and higher mortality risk (HR=1.93, 95% CI 1.37-2.77, p<0.001) than patients with normal ß2-M values. There were statistically significant differences between the C indexes for the models with IPI+ß2-M, IPI or ß2-M alone (p<0.001). CONCLUSION: Our results demonstrated an association between serum ß2-M and NHL prognosis. Combining ß2-M with IPI may help to improve the prognostic accuracy of NHL.

Peptidomics analysis of human breast milk from women with postpartum depression reveals its potential pathogenesis.

BACKGROUND: Postpartum depression (PPD) is a prevalent psychiatric disorder during the postnatal period, and it exerts adverse impacts not only on mothers but also on infants, impairing the well-being of the whole family. However, the role of peptides in the breast milk of mothers with PPD has not been studied. The purpose of this study was to unveil the peptidomic profile of PPD from breast milk samples. METHODS: We performed comparative peptidomic profiling of human breast milk from PPD and control mothers using liquid chromatography-tandem mass spectrometry technology with iTRAQ-8 labelling. GO and KEGG pathway analyses of precursor proteins were used to predict the underlying biological functions of differentially expressed peptides (DEPs). Ingenuity Pathway Analysis (IPA) was further performed to explore the interactions and involved pathways of DEPs. RESULTS: A total of 294 peptides from 62 precursor proteins were identified to be differentially expressed in the breast milk of PPD mothers compared with the control group. Bioinformatics analysis predicted that these DEPs were associated with ECM-receptor interaction, neuroactive ligand-receptor interaction, cell adhesion molecule binding and oxidative stress in macrophages. These results indicate that DEPs from human breast milk may play a part in PPD and become promising noninvasive biomarkers.

A signature based on glycosyltransferase genes provides a promising tool for the prediction of prognosis and immunotherapy responsiveness in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is the most fatal gynaecological malignancy and has a poor prognosis. Glycosylation, the biosynthetic process that depends on specific glycosyltransferases (GTs), has recently attracted increasing importance due to the vital role it plays in cancer. In this study, we aimed to determine whether OC patients could be stratified by glycosyltransferase gene profiles to better predict the prognosis and efficiency of immune checkpoint blockade therapies (ICBs). METHODS: We retrieved transcriptome data across 420 OC and 88 normal tissue samples using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, respectively. An external validation dataset containing 185 OC samples was downloaded from the Gene Expression Omnibus (GEO) database. Knockdown and pathway prediction of B4GALT5 were conducted to investigate the function and mechanism of B4GALT5 in OC proliferation, migration and invasion. RESULTS: A total of 50 differentially expressed GT genes were identified between OC and normal ovarian tissues. Two clusters were stratified by operating consensus clustering, but no significant prognostic value was observed. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, a 6-gene signature was built that classified OC patients in the TCGA cohort into a low- or high-risk group. Patients with high scores had a worse prognosis than those with low scores. This risk signature was further validated in an external GEO dataset. Furthermore, the risk score was an independent risk predictor, and a nomogram was created to improve the accuracy of prognostic classification. Notably, the low-risk OC patients exhibited a higher degree of antitumor immune cell infiltration and a superior response to ICBs. B4GALT5, one of six hub genes, was identified as a regulator of proliferation, migration and invasion in OC. CONCLUSION: Taken together, we established a reliable GT-gene-based signature to predict prognosis, immune status and identify OC patients who would benefit from ICBs. GT genes might be a promising biomarker for OC progression and a potential therapeutic target for OC.

Association of formaldehyde concentration with depression risk in US adults: a population-based epidemiology study.

The association of formaldehyde exposure with depression remains unknown. We used the data from National Health and Nutrition Examination Survey (NHANES) 2015-2016 to evaluate the association between formaldehyde exposure and depression. Multivariable logistic regressions and restricted cubic spline (RCS) were implemented to examine the association between formaldehyde exposure and depression. A total of 1336 participants were included in the analysis, of which 110 (8.23%) participants were depressed. After adjusting for confounders, a significant association between formaldehyde exposure and depression (OR = 1.01, 95% CI: 1.00-1.02, P = 0.043) was observed. The RCS plot showed a positive association in a linear manner (PNonlinear = 0.109), and the risk began to rise rapidly with concentrations above 129.37 nmol/g HB. The positive association remained in participants with high-intensity physical activity (OR = 1.08, 95% CI: 1.02-1.13, P = 0.003), but not in participants with other physical activities. Moreover, we constructed a novel nomogram to easily estimate the individual-specific probabilities of depression. In conclusion, formaldehyde exposure was associated with an elevated risk of depression, and the effect exhibited differences in participants with different levels of physical activity.

Serum Concentrations of Benzaldehyde, Isopentanaldehyde and Sex Hormones: Evidence from the National Health and Nutrition Examination Survey.

Exposure to environmental chemicals could disturb the balance of sex hormones. However, the studies on Benzaldehyde, Isopentanaldehyde exposure and sex hormones are still limited. Based on the data of 1064 participants in the National Health and Nutrition Examination Survey (NHANES), we used the linear regression model and restricted cubic spline (RCS) model to evaluate the associations of Benzaldehyde/Isopentanaldehyde exposure with testosterone (TT), estradiol (E2), sex hormone binding globulin (SHBG), free androgen index (FAI) and the ratio of TT to E2 (TT/E2). A ln-unit increase in Benzaldehyde was associated with lower TT (ß = -0.048, P = 0.030) and E2 (ß = -0.094, P = 0.046) in all participants. After further adjustment for menopausal status, Benzaldehyde was negatively associated with E2 (ß = -0.174, P = 0.045) in females. The interaction between Benzaldehyde and gender was significant (Pinter = 0.031). However, Isopentanaldehyde showed a positive association with SHBG and TT/E2 in all participants (all P < 0.05). The positive associations of Isopentanaldehyde with TT, SHBG and TT/E2 were found in males but not in females. RCS plots illustrated the linear associations of Benzaldehyde with E2 (Pnon-linear = 0.05) in females and Isopentanaldehyde with TT (Pnon-linear = 0.07) and TT/E2 (Pnon-linear = 0.350) in males. The non-linear relationships were identified between Isopentanaldehyde and SHBG in males (Pnon-linear = 0.035). Our findings indicated the effects of Benzaldehyde and Isopentanaldehyde exposure on sex hormones, and the effects had the gender specificity. Cohort studies and high-quality in vitro and in vivo experiments are needed to confirm the specific effects and uncover the underlying mechanisms.