Application of a newly constructed NGS panel with 45 X-linked microhaplotypes demonstrates the unique value of X-MH for kinship testing and mixture analysis.

X-linked microhaplotypes (X-MHs) have the potential to be a valuable supplementary tool in complex kinship identification or the resolution of DNA mixtures, because they bring together the distinctive genetic pattern of X chromosomal markers and the benefits of microhaplotypes (MHs). In this study, we used the 1000 Genome database to screen and select 63 X-MHs; 18 MHs were filtered out though a batch sequencing assessment of the DNA samples collected from 112 unrelated Chinese Han individuals. The resulting 45-plex panel performed well in comprehensive assessments including repeatability, sensitivity, species specificity, resistance to PCR inhibitors or degradation, mutation rate, and accuracy in detecting DNA mixture samples. The minimum amount of DNA template that can be tested with this panel is 0.5 ng. Additionally, the alleles of the minor contributor can be accurately detected when the mixture rate is larger than 1:9 in female-male mixture or 1:19 in male-male mixture. Then, we calculated population parameters on each MH based on the allele frequency data obtained from the sequence results of the aforementioned 112 unrelated samples. Combining these parameters on each MH, it can be calculated that TDPm, TDPf, CPET, CPEDFM, CPEDFF and CNCEP3 of the 45-plex system were 1-8.99×10-13, 1-1.62×10-19, 0.9999999995, 0.9999981, 0.9955, 0.9999971 and 0.99940, respectively, indicating that the panel is capable in personal identification and parentage testing. To reveal the unique advantage of X-MHs in the analyses of complex kinship and male DNA mixture, further assessments were made. For complex kinship identification, 22 types of individual pairs with different second-degree kinship were simulated and different types of likelihood ratios (LR) were calculated for each. The results revealed that the panel can achieve accuracy of approximately 70 %∼80 % when dividing each of the three types of second-degree kinships into three or four groups. Theoretically, such sub-division cannot be done by using independent autosomal markers. For male DNA mixture analysis without suspects, the maximum likelihood ratio strategy was derived and employed in the estimation of the number of male contributors (NOMC). Simulations were conducted to verify the efficacy of the 45-plex panel in the field and to compare it with autosomal markers by assuming the 45 MHs as autosomal ones. The results showed that X-MHs can achieve higher accuracy in the estimation of NOMC than autosomal ones when the mixed males were unrelated. The results highlighted the unique value of X-linked MHs in complex kinship and male mixture analyses.

Linking the assessment of ecological engineering construction with zoning management in the typical agro-pastoral area of China: A perspective from quantity, quality and function.

Combatting land damage has become a global priority, and China has adopted a series of ecological engineering measures, especially in the agro-pastoral area with fragile ecological environment. The effectiveness of ecological engineering construction (EEC), from a comprehensive recognition encompassing its quality, quantity, and function, has remained largely unknown. To this end, Zhangbei County, a typical agro-pastoral ecotone of northern China, was chosen as our focal area. After summarizing the timelines, aims and results of the EEC during various periods in Zhangbei, the linear spectral mixture analysis was employed to process Landsat 5 TM images in 2000 and 2010, as well as Landsat 8 OLI images in 2020. Then, a comprehensive evaluation framework of EEC was established from the perspective of "quantity-quality-function", and the ecological effectiveness of EEC was evaluated from 2000 to 2020 in Zhangbei. Results revealed that EEC played a critical role in enhancing quantity, quality and function, in spite of that, there were still numerous regions showing varying degrees of degradation in terms of these aspects. Then, by extending the three-dimensional cube as the theoretical basis for the zoning management of EEC, we merged four zones according to the space matching relationship among quantity, quality and function of EEC, namely, Ecological conservation area, Ecological improvement area, Ecological restoration area and Ecological remodeling zone. More targeted ecological measures were required for specific matching relationship among quantity, quality and function of EEC. This study is expected to present an empirical case for assessing the ecological effectiveness of EEC in areas or countries with similar restoration demand and support regional management.

Association of exposure to a mixture of phenols, parabens, and phthalates with altered serum thyroid hormone levels and the roles of iodine status and thyroid autoantibody status: A study among American adults.

BACKGROUND: Toxicological and epidemiological studies have shown that environmental endocrine disruptors interfere with hormonal homeostasis. However, there is limited research on the effects of mixed exposure to nonpersistent endocrine disruptors on thyroid hormones and the factors (e.g., presence status of thyroid autoantibodies or nutritional status of organismal iodine) that may influence this association. METHODS: Data were collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2008 and 2011-2012. Relationships between single pollutants and thyroid hormone and thyroid autoantibody levels were assessed using generalized linear (GLM) and restricted cubic spline (RCS) regression models. Weighted quantile sum regression (WQS), group-weighted quantile sum regression (GWQS), quantile-based g-computation (qgcomp), and adaptive elasticity network (AENET) were applied to assess the mixed exposure effect. Next, subgroup analyses were performed on the basis of the urinary iodine concentration or thyroid autoantibody status to assess the modifying role of urinary iodine and thyroid autoantibodies. RESULTS: A total of 2385 study participants were included in this study. Both the single-pollutant model and the multipollutant mixed model revealed that parabens and bis(2-ethylhexyl) phthalate (DEHP) metabolites were significantly and negatively associated with serum thyroxine (T4) levels. However, no associations were found between the target pollutants and thyroid autoantibodies (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)). In addition, this study revealed that urinary iodine or thyroid autoantibody status altered the associations of some of the target pollutants with thyroid hormones. WQS and qgcomp analyses, revealed that the associations of mixed pollutants with hormones differed depending on the urinary iodine or antibody status, especially T4 and thyroid-stimulating hormone (TSH). CONCLUSION: Significant associations were found between phenols, parabens, and phthalates and serum thyroid hormone levels, with parabens and DEHP metabolites playing major roles. Urinary iodine and thyroid autoantibody status act as modifiers between environmental endocrine-disrupting pollutants and thyroid hormones.

Breast cancer immunophenotypes and serum organochlorine pesticides in Mexican women: Mixture exposure approach.

Epidemiological studies on associations between breast cancer (BC) and organochlorine pesticides (OCP) are inconclusive. The majority of studies have evaluated the effect of single compounds without considering multiple OCP exposures and immunophenotypes of BC. We aimed to evaluate the association between BC immunophenotypes and serum OCP mixtures, and identify the main contributors within mixtures. We included 767 histopathologically confirmed incident BC cases and 908 controls from a population-based case-control study conducted from 2007 to 2011 in Northern Mexico. We obtained direct information about sociodemographic, lifestyle and reproductive characteristics. We collected data from clinical records about hormonal receptors (HR) and epidermal growth factor receptor 2 (HER2) expressions. Immunophenotypes were determined as HR+/HER2-, HER2+ or HR-/HER2-. We quantified OCP and metabolites by gas chromatography using an electron capture micro detector. We used Weighted Quantile Sum regression to assess the association of BC and exposure to multiple OCP, and their contribution within the mixture. We found a positive adjusted association between BC and an OCP mixture (OR: 3.48, 95%CI: 2.58, 4.69), whose primary contribution arose from the isomers of hexachlorocyclohexane and endosulfan, as well as endosulfan sulfate. We also identified a mixture negatively associated (OR: 0.13, 95%CI: 0.08, 0.20), characterized by p,p'-DDT and chlordane metabolites. All these associations remained regardless BC immunophenotypes. This is the first epidemiological report that identified serum OCP mixtures associated with BC immunophenotypes. Due to OCP ubiquity, biomagnification, and continuous exposure, they constitute a global problem of persistent exposure that might be related to BC risk.

The association of manganese overexposure and neurobehavioral function is moderated by arsenic: A metal mixture analysis of children living near coal ash storage sites.

Manganese is an essential element but can be neurotoxic if overexposed. Our previous study found that a higher level of manganese in nail biomarkers from children living near coal ash storage sites was associated with poorer neurobehavioral function. Children living near this type of pollution may be exposed to other metal neurotoxicants and a better understanding of manganese in the context of multiple exposures is needed. Mixture analyses were completed using nail samples from 251 children aged 6-14 years old. These biomarkers containing metals known to impact brain functioning were investigated to test our hypothesis that a mixture of metals including manganese impacts the development of children living near coal ash sites. Nails collected from children were analyzed using ICP-MS for manganese, arsenic, cadmium, lead, and zinc based on previous research on neurotoxicity. Bayesian kernel machine regression (BKMR) was used while adjusting for age, sex, and maternal education as potential covariates. Children also completed the Behavioral Assessment Research System (BARS) to provide neurobehavioral measures of attention and processing speed as outcomes for mixture analyses. Metal mixture analyses indicated that the relationship of manganese concentration and attention and processing speed was moderated by arsenic.,. When nail biomarkers for arsenic were highest (90th percentile), manganese was associated with poorer neurobehavioral performance on the BARS, measured by CPT hit latency. At low levels of arsenic (10th percentile), there was no evidence of harmful effects from overexposure to manganese on CPT hit latency based on BKMR analysis. Previously reported effects of manganese on neurobehavioral function may be moderated by arsenic exposure. Metal exposures and behavior outcomes can be studied with mixture analyses such as BKMR to evaluate effects of simultaneous exposures on children exposed to pollution.

A tale of two PG systems: A comparison of the two most widely used continuous probabilistic genotyping systems in the United States.

The development of probabilistic genotyping (PG) systems to quantitatively analyze DNA mixture samples has been transformative in forensic science. TrueAllele® Casework (TA) and STRmix™ (STRmix) are the two most widely used PG systems in the United States. The two systems were challenged with 48 two-, three-, and four-person mock casework samples, for a total of 152 likelihood ratio (LR) comparisons. TA and STRmix converged on the same result (supportive, non-supportive, or inconclusive) for ~91% of contributor-specific comparisons. Where moderate or substantial differences in log(LR) values were observed, 9% affected the conclusion of the reference association to the mixture. The PG systems exhibited high correlations for estimated contributor-specific template quantities (~92%) and log(LR)s produced (>88%). When the log(LR)s for only low-template contributors (<100 pg) were compared, the R2 value dropped to ~68% and the difference became statistically significant. Of the 14 contributor comparisons where the conclusion differed, two were contradictory (supportive vs. non-supportive) and 12 were either inconclusive versus non-supportive or inconclusive versus supportive. The differing results were likely due to dissimilarities in the mixture input file as STRmix uses a lab-defined analytical threshold (AT) and TA models to 10 RFUs for each electropherogram. When 7 of the 14 mixtures were reanalyzed by STRmix using a 10 RFU AT, the log(LR)s for the low-template contributors became more similar to TAs. This study shows that while both systems may produce accurate and calibrated LRs, their results can deviate, especially for low-template, degraded contributors, and the deviation is generally predictable.

Identifying patterns of multidimensional self-compassion in Chinese young adults: implications for longitudinal mental health outcomes during the pandemic.

BACKGROUND: Self-compassion (SC), reflecting self-attitude and self-connectedness, has proven to be a modifiable factor in promoting mental health outcomes. Increasingly, SC is recognized as a multidimensional construct consisting of six dimensions, rather than a single dimension. OBJECTIVES: First, this study adopted a person-centered approach to explore profiles of SC dimensions in Chinese young adults. Second, the study examined the predictive effects of SC profiles on mental health outcomes. METHODS: In February 2020, young adults (N = 1164) were invited to complete the 26-item Neff's Self-Compassion Scale online. Three months later, the same subjects (N = 1099) reported their levels of depressive symptoms, posttraumatic stress disorder (PTSD) symptoms, and posttraumatic growth (PTG). RESULTS: After controlling for retrospective ACEs, four classes best characterized the profiles: self-compassionate (26.7%, N = 294), self-uncompassionate (12.3%, N = 135), average (55.9%, N = 614), and detached groups (5.1%, N = 56). Young adults in the self-compassionate group adjusted the best (with the highest level of PTG and the lowest levels of depressive and PTSD symptoms). Adults in the self-uncompassionate group demonstrated the poorest mental health outcomes (with the lowest level of PTG and the highest levels of depressive and PTSD symptoms). Young adults in the average group obtained more PTG than adults in the detached group (p < .01), but did not differ significantly in depressive and PTSD symptoms (p > .05). CONCLUSION: The compassionate profile is the most adaptable for young adults among all groups. This study highlights the limitations of representing the relative balance of SC with a composite score.

Diabetes mellitus and serum organochlorine pesticides mixtures in Mexican women.

BACKGROUND: Very recently, it has been reported that exposure to different mixtures of organochlorine pesticides (OCP) is associated with the development of diabetes mellitus (DM). In Mexico, DM is a public health problem that might be related to the historical intense use of OCP. We aimed to evaluate, the association between DM and serum concentrations of OCP mixtures, and identify the main contributors within them. METHODS: We conducted a secondary cross-sectional analysis on the control group from a breast cancer population-based case-control study conducted from 2007 to 2011 in Northern Mexico. We identified 214 self-reported diabetic women and 694 non-diabetics. We obtained direct information about sociodemographic, lifestyle and reproductive characteristics. We determined 24 OCP and metabolites in serum by gas chromatography using an electron capture micro detector. We used Weighted Quantile Sum regression to assess the association of DM and exposure to multiple OCP, and the contribution of each compound within the mixture. RESULTS: We found a positive adjusted association between DM and an OCP mixture (OR: 2.63, 95%CI: 1.85, 3.74), whose primary contribution arose from p, p'-DDE (mean weight 23.3%), HCB (mean weight 17.3%), trans nonachlor (mean weight 15.4%), o, p'-DDE (mean weight 7.3%), heptachlor epoxide (mean weight 5.9%), oxychlordane (mean weight 4.7%), and heptachlor (mean weight 4.5%). In addition, these OCP along with p, p'-DDT and cis chlordane, were of concern and remained associated when excluding hypertensive women from the analysis (OR 2.55; 95% CI 1.56, 4.18). CONCLUSIONS: Our results indicate, for the first time in a Latin-American population, that the concomitant exposure to multiple OCP is associated with DM. Further research is needed since the composition of OCP mixtures may vary according to regional pesticides use patterns.

Prenatal exposure to polycyclic aromatic hydrocarbons and executive functions at school age: Results from a combined cohort study.

BACKGROUND: Executive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair healthy executive function development in children. There is increasing concern regarding polycyclic aromatic hydrocarbons (PAHs) given their ability to transfer across the placenta and the fetal blood-brain barrier, yet evidence from epidemiological studies is limited. METHODS: We examined associations between prenatal PAH exposure and executive functions in 814 children of non-smoking mothers from two U.S. cohorts in the ECHO-PATHWAYS Consortium. Seven mono-hydroxylated PAH metabolites were measured in mid-pregnancy urine and analyzed individually and as mixtures. Three executive function domains were measured at age 8-9: cognitive flexibility, working memory, and inhibitory control. A composite score quantifying overall performance was further calculated. We fitted linear regressions adjusted for socio-demographics, maternal health behaviors, and psychological measures, and examined modification by child sex and stressful life events in pregnancy. Bayesian kernel machine regression was performed to estimate the interactive and overall effects of the PAH mixture. RESULTS: The results from primary analysis of linear regressions were generally null, and no modification by child sex or maternal stress was indicated. Mixture analyses suggested several pairwise interactions between individual PAH metabolites in varied directions on working memory, particularly interactions between 2/3/9-FLUO and other PAH metabolites, but no overall or individual effects were evident. CONCLUSION: We conducted a novel exploration of PAH-executive functions association in a large, combined sample from two cohorts. Although findings were predominantly null, the study carries important implications for future research and contributes to evolving science regarding developmental origins of diseases.

Associations between exposure to phthalates and liver function among women undergoing assisted reproductive technology.

Phthalates can induce hepatotoxicity in animal studies. We aimed to assess the associations of individual and mixture of urinary phthalate metabolites with serum liver function indicators among 764 women undergoing assisted reproductive technology (ART). In linear models, we observed inverse correlations between urinary mono-benzyl phthalate and serum total protein (TP) as well as globulin (ß=-0.27 and -0.23, respectively, P<0.05). Additionally, negative associations were identified between mono-isobutyl phthalate and mono-butyl phthalate (MBP) and aspartate aminotransferase-to-alanine transaminase ratio (AST/ALT) (P<0.05). MBP and the sum of all phthalate metabolites (∑all.phth.m) were positively associated with bilirubin, with ß ranging from 0.14 to 0.47. Most phthalate metabolites were also positively related to gamma-glutamyl transferase (GGT) (all P<0.05). In Bayesian kernel machine regression models, phthalate mixture was positively associated with bilirubin and GGT, whereas inversely associated with AST/ALT and TP. Our results suggest that phthalate exposure may impair liver function among women undergoing ART.

Artificial Intelligence-Enhanced Waveguide "Photonic Nose"- Augmented Sensing Platform for VOC Gases in Mid-Infrared.

On-chip nanophotonic waveguide sensor is a promising solution for miniaturization and label-free detection of gas mixtures utilizing the absorption fingerprints in the mid-infrared (MIR) region. However, the quantitative detection and analysis of organic gas mixtures is still challenging and less reported due to the overlapping of the absorption spectrum. Here,an Artificial-Intelligence (AI) assisted waveguide "Photonic nose" is presented as an augmented sensing platform for gas mixture analysis in MIR. With the subwavelength grating cladding supported waveguide design and the help of machine learning algorithms, the MIR absorption spectrum of the binary organic gas mixture is distinguished from arbitrary mixing ratio and decomposed to the single-component spectra for concentration prediction. As a result, the classification of 93.57% for 19 mixing ratios is realized. In addition, the gas mixture spectrum decomposition and concentration prediction show an average root-mean-square error of 2.44 vol%. The work proves the potential for broader sensing and analytical capabilities of the MIR waveguide platform for multiple organic gas components toward MIR on-chip spectroscopy.

Association between endocrine-disrupting chemical mixtures and non-alcoholic fatty liver disease with metabolic syndrome as a mediator among adults: A population-based study in Korea.

Endocrine-disrupting chemicals (EDCs) may play a role in non-alcoholic fatty liver disease (NAFLD); however, studies on the combined effects of EDC mixtures on NAFLD development are limited. Here, we explored the association between exposure to EDC mixtures and NAFLD and investigated the potential mediating role of metabolic syndrome (MetS). We included participants from the Korean National Environmental Health Survey Cycle 4 (2018-2020) and quantified the urinary concentrations of various EDCs-eight phthalate metabolites, three phenols, one antibacterial compound, four parabens, four polycyclic aromatic hydrocarbons, and one pyrethroid pesticide metabolite-as well as serum concentrations of five perfluorinated compounds (PFCs). NAFLD was defined as a hepatic steatosis index (HSI) ≥36 or a fatty liver index (FLI) ≥60. Weighted quantile sum (WQS) regression was employed to evaluate the associations between EDC mixtures and the risk of MetS or NAFLD. Causal mediation analysis was conducted to explore the potential mediating effect of MetS on the association between mixtures of EDCs and NAFLD risk. All estimates were adjusted for age, sex, educational level, physical activity, smoking status, involuntary smoking, and drinking habits. A total of 2942 adults were included in the analysis. Moderate-to-high positive correlations were identified between phthalate metabolites and PFCs. Higher WQS scores were associated with an elevated risk of MetS and NAFLD. The sex-stratified WQS regression model showed that the interactions between the WQS index and sex were significant for MetS and NAFLD. According to the causal mediation analysis, both the direct and indirect effects of EDC mixtures on NAFLD, with MetS as a mediator, were significant in females. Collectively, these findings highlight the need for interventions that could address both EDC mixture exposure and metabolic status to effectively reduce the risks associated with NAFLD and its related complications.

Gas Graph Convolutional Transformer for Robust Generalization in Adaptive Gas Mixture Concentration Estimation.

Gas concentration estimation has a tremendous research significance in various fields. However, existing methods for estimating the concentration of mixed gases generally depend on specific data-preprocessing methods and suffer from poor generalizability to diverse types of gases. This paper proposes a graph neural network-based gas graph convolutional transformer model (GGCT) incorporating the information propagation properties and the physical characteristics of temporal sensor data. GGCT accurately predicts mixed gas concentrations and enhances its generalizability by analyzing the concentration tokens. The experimental results highlight the GGCT's robust performance, achieving exceptional levels of accuracy across most tested gas components, underscoring its strong potential for practical applications in mixed gas analysis.

Assessing the combined effect of multiple metal exposures on pregnancy and birth outcomes: Methodological insights in systematic review research.

This systematic review focused on pregnant women and aimed to evaluate how exposure to multiple metals impacts their pregnancy and birth outcomes. Previous research has predominantly focused on the effects of individual metal exposures on adverse birth outcomes. However, it is crucial to recognize that real-world scenarios often involve simultaneous exposure to multiple pollutants. Recent studies have emphasized the significance of considering exposure to mixtures of metals to gain a more comprehensive understanding of their collective health impacts. This article outlines the essential steps taken during the systematic review process, which involved synthesizing existing evidence and evaluating the strength and consistency of the relationship between metal mixtures and pregnancy and birth outcomes.

Associations of chronic exposure to a mixture of pesticides and type 2 diabetes mellitus in a Chinese elderly population.

Epidemiological studies have related exposure to pesticides to increased risk of diabetes. However, few studies have evaluated the health effects of mixed pesticides exposure, especially in an elderly population. Here, we utilized gas chromatography-tandem mass spectrometry to quantify the levels of 39 pesticides in 4 categories in a Chinese elderly population. Then we used general linear models to explore the association between individual pesticide exposure and type 2 diabetes mellitus (T2DM). Restricted cubic spline (RCS) models were fitted to identify potential non-linearities between those associations. Furthermore, stratified analysis by gender was conducted to explore the gender-specific associations. Finally, we used weighted quantile sum (WQS) regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR) to evaluate the effects of mixed exposure to 39 pesticides. The results showed that exposure to pesticides was associated with high risk of T2DM, with ß-Hexachlorocyclohexane (ß-BHC) and oxadiazon being the most significant independent contributors, which was pronounced among elderly women. Moreover, the association of ß-BHC and oxadiazon with T2DM was linear. These indicated that it is an urgent need to take practical measures to control these harmful pesticides.

Prenatal exposures to phthalates and bisphenols in relation to oxidative stress: single pollutant and mixtures analyses.

Prenatal exposures to phthalates and bisphenols have been shown to be linked with adverse birth outcomes. Oxidative stress (OS) is considered a potential mechanism. The objective of this study was to explore the individual and mixtures of prenatal exposures to phthalates and bisphenols in associations with OS biomarkers. We measured eight phthalate metabolites and three bisphenols in the urine samples from 105 pregnant women in Wuhan, China. Urinary 8-hydroxydeoxyguanosine (8-OHdG), 8-isoprostaglandin F2α (8-isoPGF2α), and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) were determined as OS biomarkers. The OS biomarkers in associations with the individual chemicals were estimated by linear regression models and restricted cubic spline (RCS) models, and their associations with the chemical mixtures were explored by quantile g-computation (qg-comp) models. In single-pollutant analyses, five phthalate metabolites including monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-(2-ethylhexyl) phthalate (MEHP), (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were positively associated with urinary 8-OHdG levels (all FDR-adjusted P = 0.06). These associations were further confirmed by the RCS models and were linear (P for overall association ≤ 0.05 and P for non-linear association > 0.05). In mixture analyses, qg-comp models showed that a one-quartile increase in the chemical mixtures of phthalate metabolites and bisphenols was positively associated with urinary levels of 8-OHdG and 8-isoPGF2α, and bisphenol A (BPA) and bisphenol F (BPF) were the most contributing chemicals, respectively. Prenatal exposures to individual phthalates and mixtures of phthalates and bisphenols were associated with higher OS levels.

Low-field, not low quality: 1D simplification, selective detection, and heteronuclear 2D experiments for improving low-field NMR spectroscopy of environmental and biological samples.

Understanding environmental change is challenging and requires molecular-level tools to explain the physicochemical phenomena behind complex processes. Nuclear magnetic resonance (NMR) spectroscopy is a key tool that provides information on both molecular structures and interactions but is underutilized in environmental research because standard "high-field" NMR is financially and physically inaccessible for many and can be overwhelming to those outside of disciplines that routinely use NMR. "Low-field" NMR is an accessible alternative but has reduced sensitivity and increased spectral overlap, which is especially problematic for natural, heterogeneous samples. Therefore, the goal of this study is to investigate and apply innovative experiments that could minimize these challenges and improve low-field NMR analysis of environmental and biological samples. Spectral simplification (JRES, PSYCHE, singlet-only, multiple quantum filters), selective detection (GEMSTONE, DREAMTIME), and heteronuclear (reverse and CH3/CH2/CH-only HSQCs) NMR experiments are tested on samples of increasing complexity (amino acids, spruce resin, and intact water fleas) at-high field (500 MHz) and at low-field (80 MHz). A novel experiment called Doubly Selective HSQC is also introduced, wherein 1H signals are selectively detected based on the 1H and 13C chemical shifts of 1H-13C J-coupled pairs. The most promising approaches identified are the selective techniques (namely for monitoring), and the reverse and CH3-only HSQCs. Findings ultimately demonstrate that low-field NMR holds great potential for biological and environmental research. The multitude of NMR experiments available makes NMR tailorable to nearly any research need, and low-field NMR is therefore anticipated to become a valuable and widely used analytical tool moving forward.

Review on NMR as a tool to analyse natural products extract directly: Molecular structure elucidation and biological activity analysis.

INTRODUCTION: Natural products, the small organic molecules produced by plants, microbes and invertebrates, often present in the form of a mixture, this leads to the structural characterisation of natural extracts often requiring time-consuming multistep purification procedures. Nuclear magnetic resonance (NMR) technology is traditionally utilised as a tool for the structural elucidation of pure compounds. Contemporarily, an up-to-date trend in the application of NMR in natural product research is shifting to the direct NMR analysis of crude mixtures, to obtain molecular structure and biological activity information without performing cumbersome separation. OBJECTIVE: To review works of literature on the evolution, principle and progress of NMR technologies for analysing mixtures, we focus on the successful application of NMR technologies in direct analysis of natural product extracts. METHODOLOGY: Based on our research experience, academic tracking and extensive literature search, which involved, but not limited to, the use of various databases, like Web of Knowledge and PubMed. The keywords used, in various combinations, to retrieve recent literature on the successful application of NMR technologies to sheer natural product extracts, and excluded artificially natural product mixture and biofluid. RESULTS: NMR technologies for direct natural extracts analysis, including two-dimensional J-resolved spectroscopy (2D-JRES), pure shift NMR, diffusion-ordered NMR spectroscopy (DOSY), statistical correlation spectroscopy (STOCSY), concentration-ordered NMR spectroscopy (CORDY), saturation transfer difference (STD) and water-ligand observed via gradient spectroscopy (WaterLOGSY) were illustrated. CONCLUSIONS: By these methods, molecular structure and biological activity information will be directly obtained from NMR analysis of natural products extract, aiming to save experimental time and expenses.

Phthalate metabolites in urine and follicular fluid in relation to menstrual cycle characteristics in women seeking fertility assistance.

BACKGROUND: Phthalates have been shown to disrupt the estrous cycle in animal studies. However, epidemiological research investigating their associations with menstrual cycle characteristics is limited. OBJECTIVE: To explore the relationships between phthalate exposure and menstrual cycle characteristics among women seeking fertility assistance. METHODS: We determined the levels of eight phthalate metabolites in both follicular fluid (FF) and urine specimens collected from 441 women in the Tongji Reproductive and Environmental (TREE) cohort, using high-performance liquid chromatography and tandem mass spectrometry. Information about menstrual cycle parameters was obtained through a questionnaire. The impacts of individual and joint exposure to phthalates on menstrual cycle characteristics were assessed using multivariable linear regression, Poisson regression, and quantile g-computation approaches. RESULTS: After adjusting for relevant covariates, we found that per log10-unit increase in mono(2-ethylhexyl) phthalate (MEHP) level in urine specimens was associated with a decrease of 0.20 days (95 % CI: -0.37, -0.03) in bleeding duration. We also observed that mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and the sum of di(2-ethylhexyl) phthalate (DEHP) metabolites (∑DEHP) concentrations in FF samples were inversely related to cycle length [ß = -1.92 (95 % CI: -3.10, -0.75) and -1.87 (95 % CI: -3.56, -0.19), respectively]. However, we generally observed null associations between phthalate metabolites and irregular cycle, dysmenorrhea, hypomenorrhea, or cycle length variation. Furthermore, we also found that phthalate metabolite mixtures in FF and urine were generally unrelated to menstrual cycle characteristics. CONCLUSION: Our findings suggest that some DEHP metabolites in FF and urine are inversely associated with menstrual cycle length and menstrual bleeding duration in women attending a fertility center.

Fish consumption and omega-3 polyunsaturated fatty acids from diet are positively associated with cognitive function in older adults even in the presence of exposure to lead, cadmium, selenium, and methylmercury: a cross-sectional study using NHANES 2011-2014 data.

BACKGROUND: Long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are reported to be beneficial for cognition, but limited consumption of some fish is recommended due to high concentrations of heavy metals and persistent organics. OBJECTIVE: We aimed to determine whether dietary ω-3 PUFAs from fish consumption are associated with higher cognitive scores in older adults and explored the associations of mixtures of ω-3 PUFAs and blood concentrations of lead, cadmium, selenium, and methylmercury on cognitive performance. METHODS: We conducted a cross-sectional study with data from the NHANES 2011-2014, assessing cognitive scores of immediate recall, delayed recall, and executive function in adults ≥60 y (n = 3123). We performed multivariate linear regressions and mixture models utilizing the quantile-based g-computation method to identify associations between monthly fish consumption or dietary ω-3 PUFAs with blood concentrations of lead, cadmium, methyl mercury, and selenium on cognitive scores. RESULTS: Fish consumption had significant positive associations with all 3 cognitive scores, whereas dietary ω-3 PUFAs were only significantly associated with the Digit Symbol Substitution Test (DSST) scores. Mixture analysis showed significant positive associations with DSST scores for fish consumption (ß: 0.88; 95% CI: 0.48, 1.29) and dietary ω-3 PUFAs (ß: 0.41; 95% CI: 0.03, 0.78) with positive component weights for fish consumption, dietary ω-3 PUFAs, and blood selenium and negative component weight for blood cadmium concentrations. CONCLUSIONS: Our findings support dietary recommendations for older adults to consume fish to maintain cognitive function, likely due to biomolecular actions of ω-3 PUFAs that increase neuronal membrane fluidity, have antioxidation activity, and restore cell damage. The combination of selenium and fish consumption or ω-3 PUFAs was associated with reduced decline in cognitive scores and less negative associations from exposures to lead, cadmium, and mercury compounds.