Metabolites, Healthy Lifestyle, and Polygenic Risk Score Associated with Upper Gastrointestinal Cancer: Findings from the UK Biobank Study.

Previous metabolomics studies have highlighted the predictive value of metabolites on upper gastrointestinal (UGI) cancer, while most of them ignored the potential effects of lifestyle and genetic risk on plasma metabolites. This study aimed to evaluate the role of lifestyle and genetic risk in the metabolic mechanism of UGI cancer. Differential metabolites of UGI cancer were identified using partial least-squares discriminant analysis and the Wilcoxon test. Then, we calculated the healthy lifestyle index (HLI) score and polygenic risk score (PRS) and divided them into three groups, respectively. A total of 15 metabolites were identified as UGI-cancer-related differential metabolites. The metabolite model (AUC = 0.699) exhibited superior discrimination ability compared to those of the HLI model (AUC = 0.615) and the PRS model (AUC = 0.593). Moreover, subgroup analysis revealed that the metabolite model showed higher discrimination ability for individuals with unhealthy lifestyles compared to that with healthy individuals (AUC = 0.783 vs 0.684). Furthermore, in the genetic risk subgroup analysis, individuals with a genetic predisposition to UGI cancer exhibited the best discriminative performance in the metabolite model (AUC = 0.770). These findings demonstrated the clinical significance of metabolic biomarkers in UGI cancer discrimination, especially in individuals with unhealthy lifestyles and a high genetic risk.

Brain extended and closed forms glutathione levels decrease with age and extended glutathione is associated with visuospatial memory.

During aging, the brain is subject to greater oxidative stress (OS), which is thought to play a critical role in cognitive impairment. Glutathione (GSH), as a major antioxidant in the brain, can be used to combat OS. However, how brain GSH levels vary with age and their associations with cognitive function is unclear. In this study, we combined point-resolved spectroscopy and edited spectroscopy sequences to investigate extended and closed forms GSH levels in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and occipital cortex (OC) of 276 healthy participants (extended form, 166 females, age range 20-70 years) and 15 healthy participants (closed form, 7 females, age range 26-56 years), and examined their relationships with age and cognitive function. The results revealed decreased extended form GSH levels with age in the PCC among 276 participants. Notably, the timecourse of extended form GSH level changes in the PCC and ACC differed between males and females. Additionally, positive correlations were observed between extended form GSH levels in the PCC and OC and visuospatial memory. Additionally, a decreased trend of closed form GSH levels with age was also observed in the PCC among 15 participants. Taken together, these findings enhance our understanding of the brain both closed and extended form GSH time course during normal aging and associations with sex and memory, which is an essential first step for understanding the neurochemical underpinnings of healthy aging.

Benzo(a)anthracene Targeting SLC1A5 to Synergistically Enhance PAH Mixture Toxicity.

Human exposure to polycyclic aromatic hydrocarbons (PAHs) as mutagenic and carcinogenic pollutants in the environment often occurs in the form of mixtures. Although the mixture effects of PAHs have been previously recognized, the toxicological mechanisms to explain them still remain quite unclear. This study combined metabolomics and chemical proteomics methods to comprehensively understand the mixture effects of a PAH mixture including benzo(a)anthracene (BaA), benzo(b)fluoranthene (BbF), benzo(a)pyrene (BaP), and chrysene (CHR). Among them, BaA has shown a strong synergistic effect with other PAHs. Interestingly, BaA alone is not a potent oxidative stress inducer in liver cells but dose-dependently amplifies oxidative damage caused by the PAH mixture. Global metabolomics analysis results revealed damage to the antioxidant glutathione synthesis, which was caused by the glutamine depletion caused by BaA in the mixture. Subsequently, the label-free chemical proteomics and cellular thermal shift analysis (CETSA) demonstrated that the PAH mixture altered the thermal shift of glutamine transporter SLC1A5. Furthermore, Western blotting and the isothermal titration calorimetry (ITC) interaction measurements showed nanomolar KD values between BaA and SLC1A5. Overall, this study showed that BaA synergistically contributed to PAH mixture induced oxidative damage by targeting SLC1A5 to inhibit glutamate transport into cells, resulting in the inhibition of glutathione synthesis.

Sex-specific, non-linear and congener-specific association between mixed exposure to polychlorinated biphenyls (PCBs) and diabetes in U.S. adults.

BACKGROUND: Whether and to what extent the impact of exposure to various polychlorinated biphenyls (PCBs) congeners on diabetes, as well as the important contributors, have remained unclear. OBJECTIVE: We aimed to investigate the association patterns between PCBs mixture and diabetes, identify the critical congeners, and explore the potential modifiers. METHODS: The present study included 5900 U.S. adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016. Weighted logistic regression, restricted cubic spline regression, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were applied to estimate the linear and non-linear associations of single and mixed PCB exposure with diabetes. Subgroup analyses were also conducted to explore potential sex differences. RESULTS: In the weighted logistic regression model, total PCBs were positively associated with diabetes (OR = 1.33, P < 0.025), and significant non-linear associations were observed using RCS analyses. The non-linear positive association between PCBs mixed exposure and diabetes was likewise found in the WQS and BKMR results. PCB180, PCB194, PCB196, and PCB167 were with the highest weights in the WQS, and PCB209 and PCB66 were with the highest posterior inclusion probabilities in the BKMR. Additionally, exposure to total PCBs and most of individual PCB congeners were significantly associated with elevated risk of in females (OR = 1.74; P for trend < 0.001), while fewer significant associations were observed in males. CONCLUSION: The present study highlighted the importance of the long-term surveillance of PCBs and the need to enhance protective measures against them. Notably, these associations were non-linear, congener-specific, and significantly stronger in females than males, especially at relatively high levels of PCBs exposure. Further prospective and mechanistic studies were warranted to ascertain the causal effects between PCBs mixture and diabetes.

Untargeted serum metabolomics reveals potential biomarkers and metabolic pathways associated with the progression of gastroesophageal cancer.

BACKGROUND: Previous metabolic studies in upper digestive cancer have mostly been limited to cross-sectional study designs, which hinders the ability to effectively predict outcomes in the early stage of cancer. This study aims to identify key metabolites and metabolic pathways associated with the multistage progression of epithelial cancer and to explore their predictive value for gastroesophageal cancer (GEC) formation and for the early screening of esophageal squamous cell carcinoma (ESCC). METHODS: A case-cohort study within the 7-year prospective Esophageal Cancer Screening Cohort of Shandong Province included 77 GEC cases and 77 sub-cohort individuals. Untargeted metabolic analysis was performed in serum samples. Metabolites, with FDR q value < 0.05 and variable importance in projection (VIP) > 1, were selected as differential metabolites to predict GEC formation using Random Forest (RF) models. Subsequently, we evaluated the predictive performance of these differential metabolites for the early screening of ESCC. RESULTS: We found a distinct metabolic profile alteration in GEC cases compared to the sub-cohort, and identified eight differential metabolites. Pathway analyses showed dysregulation in D-glutamine and D-glutamate metabolism, nitrogen metabolism, primary bile acid biosynthesis, and steroid hormone biosynthesis in GEC patients. A panel of eight differential metabolites showed good predictive performance for GEC formation, with an area under the receiver operating characteristic curve (AUC) of 0.893 (95% CI = 0.816-0.951). Furthermore, four of the GEC pathological progression-related metabolites were validated in the early screening of ESCC, with an AUC of 0.761 (95% CI = 0.716-0.805). CONCLUSIONS: These findings indicated a panel of metabolites might be an alternative approach to predict GEC formation, and therefore have the potential to mitigate the risk of cancer progression at the early stage of GEC.

Loudspeaker array beamforming for sound projection in a half-space with an impedance boundary.

Sound projection is a method of using highly focused sources to project sound onto reflective surfaces to create the impression of surround sound, which can be realized via beamforming using loudspeaker arrays. Generally, these devices are mounted near a surface with a finite acoustic impedance, such as a TV accent wall. The beamforming performance degrades in this half-space with an impedance boundary when the filters are designed using transfer functions measured in the free field. This paper proposes a model for predicting the beamforming performance in a half-space with an impedance boundary in terms of the transfer functions in the free field. A mathematical model is presented, and the results are compared with practical measurements for a 16-driver line array in real-use environments. The results show that reflections from the boundary lead to "dark bands" in the beam, causing the beam to deviate from the designed direction. Using filters designed with transfer functions calculated by the proposed model yields improved beamforming performance.

Multi-objective optimization for generation of personal sound zone.

Personal Sound Zone (PSZ) allows listeners to enjoy their individual sound without being disturbed by sound from other zones. Acoustic contrast, signal distortion, and array effort are the most frequently used metrics for measuring the performance of a PSZ system. However, usually, the three metrics cannot be optimized at the same time. A trade-off between the three metrics has to be made when designing a PSZ system. In this paper, two generalized methods based on multi-objective optimization are proposed for dealing with all possible trade-off problems between the three metrics in PSZ. Optimality analysis of the two proposed methods is taken, and the relationship between the two proposed methods is investigated. Numerical simulations are presented to validate the efficacy and flexibility of the two proposed methods.

Associations between exposure to brominated flame retardants and metabolic syndrome and its components in U.S. adults.

BACKGROUND: Humans are simultaneously exposed to numerous of environmental brominated flame retardants (BFRs). We aim to explore the overall associations of BFRs mixture on metabolic syndrome (MetS) and its components and further identify significant chemicals. METHODS: This study included 4641 adults from the National Health and Nutrition Examination Survey (NHANES) in 2007-2016. The weighted logistic regression was conducted to estimate the association of a single BFR exposure with MetS and its components. Meanwhile, the weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were adopted to evaluate the overall associations of BFRs mixture on MetS and its components, and to identify significant chemicals. We also evaluated potential associations modified by sex. RESULTS: In the weighted logistic regression model, PBB153 were positively associated with MetS in a dose-dependent manner (Ptrend < 0.05). For its components, increasing quartiles of most BFRs were positively associated with abdominal obesity, hypertriglyceridemia, and low HDL. However, we found no statistically significant associations between BFRs and hypertension and hyperglycemia. WQS analyses found that BFRs mixture was positively associated with MetS (OR: 1.30; 95%CI:1.14, 1.46), abdominal obesity (OR: 1.15; 95%CI:1.03, 1.27), hypertriglyceridemia (OR:1.43; 95%CI:1.19, 1.67), and low HDL (OR: 1.15; 95%CI:1.01, 1.29). BKMR showed associations in a similar direction as WQS for BFRs mixture. For MetS, hypertriglyceridemia and Low HDL, PBB153, PBDE28 and PBDE209 were the most heavily weighting chemicals and had the highest the posterior inclusion probabilities in the WQS and BKMR, respectively. BFRs showed stronger associations of MetS and its components in males than in females. CONCLUSIONS: The present study suggested exposure to BFRs mixture was positively associated with MetS and its components in adults, and PBB153, PBDE28 and PBDE209 were the significant chemicals. However, prospective cohort studies are still needed to confirm the causal effect between BFRs mixture and MetS.

Feasibility of an NIR spectral calibration transfer algorithm based on optimized feature variables to predict tobacco samples in different states.

The prediction accuracy of calibration models for near-infrared (NIR) spectroscopy typically relies on the morphology and homogeneity of the samples. To achieve non-homogeneous tobacco samples for non-destructive and rapid analysis, a method that can predict tobacco filament samples using reliable models based on the corresponding tobacco powder is proposed here. First, as it is necessary to establish a simple and robust calibrated model with excellent performance, based on full-wavelength PLSR (Full-PLSR), the key feature variables were screened by three methods, namely competitive adaptive reweighted sampling (CARS), variable combination population analysis-iteratively retaining informative variables (VCPA-IRIV), and variable combination population analysis-genetic algorithm (VCPA-GA). The partial least squares regression (PLSR) models for predicting the total sugar content in tobacco were established based on three optimal wavelength sets and named CARS-PLSR, VCPA-IRIV-PLSR and VCPA-GA-PLSR, respectively. Subsequently, they were combined with different calibration transfer algorithms, including calibration transfer based on canonical correlation analysis (CTCCA), slope/bias correction (S/B) and non-supervised parameter-free framework for calibration enhancement (NS-PFCE), to evaluate the best prediction model for the tobacco filament samples. Compared with the previous two transfer algorithms, NS-PFCE performed the best under various wavelength conditions. The prediction results indicated that the most successful approach for predicting the tobacco filament samples was achieved by VCPA-IRIV-PLSR when coupled with the NS-PFCE method, which obtained the highest determination coefficient (Rp2 = 0.9340) and the lowest root mean square error of the prediction set (RMSEP = 0.8425). VCPA-IRIV simplifies the calibration model and improves the efficiency of model transfer (31 variables). Furthermore, it pledges the prediction accuracy of the tobacco filament samples when combined with NS-PFCE. In summary, calibration transfer based on optimized feature variables can eliminate prediction errors caused by sample morphological differences and proves to be a more beneficial method for online application in the tobacco industry.

Prognostic model construction and immune microenvironment analysis of esophageal cancer based on gene expression data and microRNA target genes.

Background: Accumulating evidence suggests that microRNA-target genes are closely related to tumorigenesis and progression. This study aims to screen the intersection of differentially expressed mRNAs (DEmRNAs) and the target genes of differentially expressed microRNAs (DEmiRNAs), and to construct a prognostic gene model of esophageal cancer (EC). Methods: Gene expression, microRNA expression, somatic mutation, and clinical information data of EC from The Cancer Genome Atlas (TCGA) database were used. The intersection of DEmRNAs and the target genes of DEmiRNAs predicted by the Targetscan database and microRNA Data Integration Portal (mirDIP) database were screened. The screened genes were used to construct a prognostic model of EC. Then, the molecular and immune signatures of these genes were explored. Finally, the GSE53625 dataset from the Gene Expression Omnibus (GEO) database was further used as a validation cohort to confirm the prognostic value of the genes. Results: Six genes on the grounds of the intersection of DEmiRNAs target genes and DEmRNAs were identified as prognostic genes, including ARHGAP11A, H1.4, HMGB3, LRIG1, PRR11, and COL4A1. Based on the median risk score calculated for these genes, EC patients were divided into a high-risk group (n=72) and a low-risk group (n=72). Survival analysis showed that the high-risk group had a significantly shorter survival time than the low-risk group (TCGA and GEO, P<0.001). The nomogram evaluation showed high reliability in predicting the 1-year, 2-year, and 3-year survival probability of EC patients. Compared to low-risk group, higher expression level of M2 macrophages was found in high-risk group of EC patient (P<0.05), while STAT3 checkpoints showed attenuated expression level in high-risk group. Conclusions: A panel of differential genes was identified as potential EC prognostic biomarkers and showed great clinical significance in EC prognosis.

Reduced brain glutathione levels during normal aging are associated with visuospatial memory.

During aging, the brain is subject to greater oxidative stress (OS), which is thought to play a critical role in cognitive impairment. Glutathione (GSH), as a major antioxidant in the brain, can be used to combatting OS. However, how brain GSH levels vary with age and their associations with cognitive function remain unclear. In this study, we combined point-resolved spectroscopy and edited spectroscopy sequences to investigate GSH levels in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and occipital cortex (OC) of 276 healthy participants (166 females, age range 20-70 years) and examined their relationships with age and cognitive function. The results revealed decreased GSH levels with age in the PCC among all participants. Notably, the timecourse of GSH level changes in the PCC and ACC differed between males and females. Additionally, positive correlations were observed between GSH levels in the PCC and OC and visuospatial memory. Taken together, these findings enhance our understanding of the brain GSH timecourse during normal aging and associations with sex and memory, which is an essential first step for understanding the neurochemical underpinnings of OS-related diseases.

Age-Stage, Two-Sex Life Table and Functional Response of Amblyseius orientalis (Acari: Phytoseiidae) Feeding on Different Nutrient Sources.

Amblyseius orientalis Ehara is a predatory mite that belongs to the family Phytoseiidae. It is mainly found in Jiangxi, Shanghai, Guangdong, and other areas of China. Although A. orientalis is a dominant predatory mite species in China and is also important for agriculture and biological control, not many studies have investigated it. Thus, research on A. orientalis is necessary. However, its application in biological control is hindered by the absence of techniques for the mass rearing of A. orientalis in captivity. We conducted experiments to determine the growth, development, reproduction, and functional response of A. orientalis in this study by indoor single-head rearing at 25 ± 1 °C, 65 ± 5% relative humidity, and a photoperiod of a 16 h:8 h light/dark cycle under laboratory conditions. The results of the age stage, two-sex life table showed that the individuals in the pollen + yeast and pollen + yeast + sucrose groups had significantly higher oviposition period, fecundity, net reproductive rate (R0), and gross reproduction rate (GRR) than those in the pollen group. The results of the function response showed that the pollen + yeast + sucrose group was the most favorable for captive breeding of A. orientalis and had the best predatory ability along with rejuvenation and recovery ability. The results of the study provided a theoretical basis for indoor rearing, propagation, and utilization of A. orientalis.