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Increasing evidences have revealed a close relationship between various environmental exposures and reproductive health. The real-world complex exposure scenario along with intricate interactions effects of these exposures has high demands of exposome-wide association studies for human risk assessment. With the development of exposomic studies, applying hair exposome to link environmental factors and reproductive health outcomes has obvious potential advantages. However, the reliability of utilizing hair to characterize exposome is always of high concern for researchers. In this review, we briefly summarized studies about the effects of environmental exposures on several typical reproductive health outcomes, described state-of-the-art situation of applying hair exposome for reproductive health risk assessment, elucidated the advantages (e.g., containing abundant exposure factors, low expenses for sampling, and tracing exposure history), and proposed the unsolved issues in this area. We also conducted a comprehensive discussion about the reliability of various hair biomarkers and primarily established the biomarker databases. Finally, a standardized framework on using hair exposome for reproductive health study was proposed to provide fundamental approach for future studies. We concluded that it is promising to apply hair exposome to evaluate the effects of the environmental factors on human reproductive health.

Liquid crystal monomers (LCMs) are a family of synthetic organic chemicals applied in the liquid crystal displays (LCDs) of various electric and electronic products (e-products). Due to their unique properties (i.e., persistence, bioaccumulative potential, and toxicity) and widespread environmental distributions, LCMs have attracted increasing attention across the world. Recent studies have focused on the source, distribution, fate, and toxicity of LCMs; however, a comprehensive review is scarce. Herein, we highlighted the persistence and bioaccumulation potential of LCMs by reviewing their physical–chemical properties. The naming rules were suggested to standardize the abbreviations regarding LCMs. The sources and occurrences of LCMs in different environmental compartments, including dust, sediment, soil, leachate, air and particulate, human serum, and biota samples, were reviewed. It is concluded that the LCMs in the environment mainly originate from the usage and disassembly of e-products with LCDs. Moreover, the review of the potential recycling and removal technologies regarding LCMs from waste LCD panels suggests that a combination of natural attenuation and physic-chemical remediation should be developed for LCMs remediations in the future. By reviewing the health risks and toxicity of LCMs, it is found that a large gap exists in their toxicity and risk to organisms. The fate and toxicity investigation of LCMs, and further investigations on the effects on the human exposure risks of LCMs to residents, especially to occupational workers, should be considered in the future.

In this paper, we study a uniqueness question of meromorphic functions concerning fixed points and mainly prove the following theorem: Let $ f $ and $ g $ be two nonconstant meromorphic functions, let $ n, k $ be two positive integers with $ n > 3k+10.5-\Theta_{\min}(k+6.5) $, if $ \Theta_{\min}\geq \frac{2.5}{k+6.5} $, otherwise $ n > 3k+8 $, and let $ (f^{n})^{(k)} $ and $ (g^{n})^{(k)} $ share $ z $ CM, $ f $ and $ g $ share $ \infty $ IM, then one of the following two cases holds: If $ k = 1 $, then either $ f(z) = c_{1}e^{cz^{2}} $, $ g(z) = c_{2}e^{-cz^{2}} $, where $ c_{1}, c_{2} $ and $ c $ are three constants satisfying $ 4n^{2}(c_{1}c_{2})^{n}c^{2} = -1 $, or $ f = tg $ for a constant $ t $ such that $ t^{n} = 1 $; if $ k\geq2 $, then $ f = tg $ for a constant $ t $ such that $ t^{n} = 1 $. Our results extend and improve some results due to [8,9,19,24].

Bisphenol analogs (BPs) are widely used as industrial alternatives for Bisphenol A (BPA). Their toxicity assessment in humans has mainly focused on estrogenic activity, while other toxicity effects and mechanisms resulting from BPs exposure remain unclear. In this study, we investigated the effects of three BPs (Bisphenol AF (BPAF), Bisphenol G (BPG) and Bisphenol PH (BPPH)) on metabolic pathways of HepG2 cells. Results from comprehensive cellular bioenergetics analysis and nontarget metabolomics indicated that the most important process affected by BPs exposure was energy metabolism, as evidenced by reduced mitochondrial function and enhanced glycolysis. Compared to the control group, BPG and BPPH exhibited a consistent pattern of metabolic dysregulation, while BPAF differed from both, such as an increased ATP: ADP ratio (1.29-fold, p

Background: Bisphenol A (BPA), a ubiquitous environmental endocrine disruptor, has been extensively demonstrated to be associated with metabolic disorders, including obesity and type 2 diabetes mellitus. However, the underlying mechanism underpinning the environmental etiology of chronic metabolic disorders has not been sufficiently elucidated. Objectives: This study is designed to explore the toxicological pathogenesis of chronic inflammation in BPA exposure during obesity. Methods: We investigated the role of IL-17A in the association of BPA exposure and obesity from human cross-sectional study to animal models, including genetically modified IL-17A-/- mice. Results: Here, our work started from case-control observation that BPA exposure was significantly associated with risk of obesity (odds ratio = 4.72, 95%CI: 3.18 – 11.18, P

This paper is devoted to investigate the existence and the forms of entire solutions of several Fermat type quadratic trinomial differential difference equations. Our results improve some results due to Liu and Yang [An. Stiint. Univ. Al. I. Cuza Iasi. Mat., 2016], Han and Lü [J. Contemp. Math. Anal., 2019], Luo, Xu and Hu [Open Math., 2021].

Let $ f $ and $ g $ be two transcendental meromorphic functions of finite order with a Borel exceptional value $ \infty $, let $ \alpha $ $ (\not\equiv 0) $ be a small function of both $ f $ and $ g $, let $ d, k, n, m $ and $ v_j (j = 1, 2, \cdots, d) $ be positive integers, and let $ c_j (j = 1, 2, \cdots, d) $ be distinct nonzero finite values. If $ n\ge \max \{2k+m+\sigma+5, \sigma+2d+3\} $, where $ \sigma = v_1+v_2+\cdots +v_d $, and $ (f^n(z)(f^m(z)-1)\prod _{j = 1}^{d}f^{v_j}(z+c_j))^{(k)} $ and $ (g^n(z)(g^m(z)-1)\prod _{j = 1}^{d}g^{v_j}(z+c_j))^{(k)} $ share $ \alpha $ CM then $ f \equiv tg $, where $ t^m = t^{n+\sigma } = 1. $ This result extends and improves some restlts due to [1,10,14,15,19].

In this paper, we investigate the uniqueness of an entire function sharing a small function with its linear difference polynomial. Our results improve some results due to Li and Yi [11], Zhang, Chen and Huang [17], Zhang, Kang and Liao [18,19] etc.

Abstract Let c be a nonzero constant and n a positive integer, let f be a transcendental meromorphic function of finite order, and let R be a nonconstant rational function. Under some conditions, we study the relationships between the exponent of convergence of zero points of f − R $f-R$ , its shift f ( z + n c ) $f(z+nc)$ and the differences Δ c n f $\Delta _{c}^{n} f$ .

In the toxicological regime, the toxicological endpoint and its dose-response relationship are two of the most prominent characters in conducting a risk assessment for chemical exposure. Systems biological methods have been used to comprehensively characterize the impact of toxicants on the biochemical pathways. However, the majority of the current studies are only based on single-dose, and limited information can be extrapolated to other doses from these experiments, regardless of the sensitivity of each endpoint. This study aims to understand the dose-response metabolite dysregulation pattern and metabolite sensitivity at the system-biological level. Here, we applied bisphenol A (BPA), an endocrine-disrupting chemical (EDC), as the model chemical. We first employed the global metabolomics method to characterize the metabolome of breast cancer cells (MCF-7) upon exposure to different doses (0, 20, 50, and 100 µM) of BPA. The dysregulated features with a clear dose-response relationship were also effectively picked up with an R-package named TOXcms. Overall, most metabolites were dysregulated by showing a significant dose-dependent behaviour. The results suggested that BPA exposure greatly perturbed purine metabolism and pyrimidine metabolism. Interestingly, most metabolites within the purine metabolism were described as a biphasic dose-response relationship. With the established dose-response relationship, we were able to fully map the metabolite cartography of BPA exposure within a wide range of concentrations and observe some unique patterns. Furthermore, an effective concentration of certain fold changes (e.g., EC+10 means the dose at which metabolite is 10% upregulated) and metabolite sensitivity were defined and introduced to this dose-response omics information. The result showed that the purine metabolism pathway is the most venerable target of BPA, which can be a potential endogenous biomarker for its exposure. Overall, this study applied the dose-response metabolomics method to fully understand the biochemical pathway disruption of BPA treatment at different doses. Both dose-response omics strategy and metabolite sensitivity analysis can be further considered and emphasized in future chemical risk assessments.

Humans are exposed to an ever-increasing number of environmental toxicants, some of which have gradually been elucidated to be important risk factors for metabolic diseases, such as diabetes and obesity. These metabolism-sensitive diseases typically occur when key metabolic and signaling pathways were disrupted, which can be influenced by the exposure to contaminants such as endocrine disrupting chemicals (EDCs), along with genetic and lifestyle factors. This promotes the concept and research on environmental metabolism disrupting chemicals (MDCs). In addition, identifying endogenous biochemical markers of effect linked to disease states is becoming an important tool to screen the biological targets following environmental contaminant exposure, as well as to provide an overview of toxicity risk assessment. As such, the current review aims to contribute to the further understanding of exposome and human health and disease by characterizing environmental exposure and effect metabolic biomarkers. We summarized MDC-associated metabolic biomarkers in laboratory animal and human cohort studies using high throughput targeted and nontargeted metabolomics techniques. Contaminants including heavy metals and organohalogen compounds, especially EDCs, have been repetitively associated with metabolic disorders, whereas emerging contaminants such as perfluoroalkyl substances and microplastics have also been found to disrupt metabolism. In addition, we found major limitations in the effective identification of metabolic biomarkers especially in human studies, toxicological research on the mixed effect of environmental exposure has also been insufficient compared to the research on single chemicals. Thus, it is timely to call for research efforts dedicated to the study of combined effect and metabolic alterations for the better assessment of exposomic toxicology and health risks. Moreover, advanced computational and prediction tools, further validation of metabolic biomarkers, as well as systematic and integrative investigations are also needed in order to reliably identify novel biomarkers and elucidate toxicity mechanisms, and to further utilize exposome and metabolome profiling in public health and safety management.

Summary: The current human exposome primarily emphasizes the total environmental exposure during an entire life. The characteristics of “lifelong” and “all environmental factors” make it very challenging to bring the exposomic study into real-life applications. Herein, we mainly discuss the typical application scenarios of exposomics and how to conduct an exposomic study to establish relationships between the exposome and human health. To increase the feasibility and efficiency, we propose that (1) an exposomic study can start with health events during critical-window periods; (2) both data- and hypothesis-driven exposomics should be combined to prioritize the risk of environmental factors; and (3) reliable statistical analysis of high-dimensional data of external and internal exposure factors are urgently needed. With standardization of the exposomic study, it will be critical to build a “wonderland” for human health.

Over the course of the continual phase-outs of toxic halogenated flame retardants (HFRs), there has been an increasing demand for organophosphate esters (OPEs) in global FR markets. OPE-FRs have largely been identified as OP triesters, which have a basic chemical structure of O = P(OR)3. In addition to OP triesters, OPEs can refer to another class of related substances, namely, OP diesters that have a typical chemical structure of O = P(OR)2(OH)). OP diesters are known as biotic or abiotic degradation products of OP triesters. In recent years, environmental scientists have proven that OP diesters widely exist in a variety of environmental matrices and biotic samples around the world, implying the potential risks from OP diester exposure to biota and humans in the environment. Here, we have reviewed the scientific literature for studies involving OP diesters and up to the end of 2020. The aim of the present review is to assess the present understanding of the physicochemical properties, sources (industrial production and degradation), environmental occurrence of OP diesters, and adverse effects to exposed organisms. Based on the literature in the Web of Science core collection, we found that at least 23 OP diesters have been reported as contaminants in various environments or as degradation products of OP triesters. The physicochemical properties of OP diesters vary depending on their specific chemical structures. OP diesters containing halogen atoms and aryl groups seem to be more persistent (with greater estimated half-life (t1/2) values) in environmental matrices. There were multiple sources of OP diesters, including industrial production and biotic or abiotic degradation from OP triesters. Specifically, we found that ten OP diesters are produced somewhere in the world, and the total annual output was estimated to be 17,050 metric tons (this number is underestimated due to the limitation of the available information). In addition, the wide application of OP triesters worldwide makes the degradation of OP triesters another critical source of OP diesters to the environment and to organisms. Current monitoring studies have demonstrated that some OP diesters were detectable in the human body (via both blood and urine samples), indoor dust, wastewater, or sewage sludge worldwide. The highest concentrations of diphenyl phosphate (DPHP) in human urine have been reported as high as 727 ng/mL (children (aged 0–5 years) urine samples from Australia). In addition, adverse effects following direct or indirect exposure to 11 OP diesters in organisms (including animals, bacteria, and algae) have been reported, and the recorded adverse outcomes following exposure to OP diesters included developmental toxicity, alteration of gene expression, and disturbance of nuclear receptor activity. Biomonitoring studies regarding human samples have frequently reported statistically significant associations between the concentrations of OP diesters and markers of human health (mainly related to reproductive toxicity). Finally, on the basis of current knowledge on OP diesters, we propose prospects for related research directions in future studies.

Bisphenol A diglycidyl ether (BADGE)-based epoxy resin is one of the most widely used epoxy resins with an annual production amount of several million tons. Compared with all other legacy or emerging organic compounds, BADGE is special due to its toxicity and high reactivity in the environment. More and more studies are available on its analytical methods, occurrence, transformation and toxicity. Here, we provided a comprehensive review of the current BADGE-related studies, with focus on its production, application, available analytical methods, occurrences in the environment and human specimen, abiotic and biotic transformation, as well as the in vitro and in vivo toxicities. The available data show that BADGE and its derivatives are ubiquitous environmental chemicals and often well detected in human specimens. For their analysis, a water-free sample pretreatment should be considered to avoid hydrolysis. Additionally, their complex reactions with endogenous metabolites are areas of great interest. To date, the monitoring and further understanding of their transport and fate in the environment are still quite lacking, comparing with its analogues bisphenol A (BPA) and bisphenol S (BPS). In terms of toxicity, the summary of its current studies and Environmental Protection Agency (EPA) ToxCast toxicity database suggests BADGE might be an endocrine disruptor, though more detailed evidence is still needed to confirm this hypothesis in in vivo animal models. Future study of BADGE should focus on its metabolic transformation, reaction with protein and validation of its role as an endocrine disruptor. We believe that the elucidation of BADGEs can greatly enhance our understandings of those reactive compounds in the environment and human.

Abstract In this paper, we study the uniqueness problems of meromorphic functions and their difference operators. Our main result is a difference analogue of a result of Jank–Mues–Volkmann, which is concerned with the uniqueness of an entire function sharing one finite value with its derivatives. Some recent papers studied the case of entire functions of finite order sharing a periodic small function to f. We consider the case of meromorphic functions of finite order sharing a polynomial, which is a more popular case. Examples are provided for our results.

Extracting metabolic features from liquid chromatography-mass spectrometry (LC-MS) data has been a long-standing bioinformatic challenge in untargeted metabolomics. Conventional feature extraction algorithms fail to recognize features with low signal intensities, poor chromatographic peak shapes, or those that do not fit the parameter settings. This problem also poses a challenge for MS-based exposome studies, as low-abundant metabolic or exposomic features cannot be automatically recognized from raw data. To address this data processing challenge, we developed an R package, JPA (short for Joint Metabolomic Data Processing and Annotation), to comprehensively extract metabolic features from raw LC-MS data. JPA performs feature extraction by combining a conventional peak picking algorithm and strategies for (1) recognizing features with bad peak shapes but that have tandem mass spectra (MS2) and (2) picking up features from a user-defined targeted list. The performance of JPA in global metabolomics was demonstrated using serial diluted urine samples, in which JPA was able to rescue an average of 25% of metabolic features that were missed by the conventional peak picking algorithm due to dilution. More importantly, the chromatographic peak shapes, analytical accuracy, and precision of the rescued metabolic features were all evaluated. Furthermore, owing to its sensitive feature extraction, JPA was able to achieve a limit of detection (LOD) that was up to thousands of folds lower when automatically processing metabolomics data of a serial diluted metabolite standard mixture analyzed in HILIC(−) and RP(+) modes. Finally, the performance of JPA in exposome research was validated using a mixture of 250 drugs and 255 pesticides at environmentally relevant levels. JPA detected an average of 2.3-fold more exposure compounds than conventional peak picking only.

The application of tetracycline (TET) is very common in medical treatment, fisheries, and animal husbandry, resulting in its frequent detection with abundant concentrations in the aquatic environment. Though the effects of TET on zebrafish (Danio rerio) at embryonic and larval stages have been reported, there is very limited information on the possible long-term effect on aquatic fishes at the juvenile stage, especially at environmentally relevant levels. In this study, we have exposed juvenile zebrafish to two levels of TET at 1 and 100 µg/L for one month until their adulthood. The result showed that both levels of TET can significantly increase the body weight of the zebrafish, while there is no change in the body length. TET exposure also affected the liver microstructure by lipid vacuoles generation and global lipidomics analysis revealed a significant upregulation in hepatic triglyceride (TAG) levels. The metabolomics analysis showed great dysregulations in hepatic metabolic pathways including linoleic acid metabolism, tyrosine metabolism, and methionine metabolism, which are known to be linked with increased body weight gain through hepatic lipid accumulation. The hepatic gene expression involved in lipid transport (e.g., apoa4 and fabp11) and lipogenic factors (e.g., ppar) have been significantly upregulated in the livers of TET exposed zebrafish. Interestingly, the 16 rRNA gene sequence-based zebrafish gut microbial community analysis revealed an enhanced community diversity and altered microbial community composition upon TET exposure. To our knowledge, this is the first study showing that TET exposure can increase the body weight in juvenile zebrafish and the study on the ecotoxicity of antibiotic occurrences in the aquatic system can be further warranted.

Objectives: Extracts of the hops plant have been shown to reduce weight and insulin resistance in rodents and humans, but elucidation of the mechanisms responsible for these benefits has been hindered by the use of heterogeneous hops-derived mixtures. Because hop extracts are used as flavoring agents for their bitter properties, we hypothesized that bitter taste receptors (Tas2rs) could be mediating their beneficial effects in metabolic disease. Studies have shown that exposure of cultured enteroendocrine cells to bitter tastants can stimulate release of hormones, including glucagon-like peptide 1 (GLP-1). These findings have led to the suggestion that activation of Tas2rs may be of benefit in diabetes, but this tenet has not been tested. Here, we have assessed the ability of a pure derivative of a hops isohumulone with anti-diabetic properties, KDT501, to signal through Tas2rs. We have further used this compound as a tool to systematically assess the impact of bitter taste receptor activation in obesity-diabetes. Methods: KDT501 was tested in a panel of bitter taste receptor signaling assays. Diet-induced obese mice (DIO) were dosed orally with KDT501 and acute effects on glucose homeostasis determined. A wide range of metabolic parameters were evaluated in DIO mice chronically treated with KDT501 to establish the full impact of activating gut bitter taste signaling. Results: We show that KDT501 signals through Tas2r108, one of 35 mouse Tas2rs. In DIO mice, acute treatment stimulated GLP-1 secretion and enhanced glucose tolerance. Chronic treatment caused weight and fat mass loss, increased energy expenditure, enhanced glucose tolerance and insulin sensitivity, normalized plasma lipids, and induced broad suppression of inflammatory markers. Chronic KDT501 treatment altered enteroendocrine hormone levels and bile acid homeostasis and stimulated sustained GLP-1 release. Combined treatment with a dipeptidyl peptidase IV inhibitor amplified the incretin-based benefits of this pure isohumulone. Conclusions: Activation of Tas2r108 in the gut results in a remodeling of enteroendocrine hormone release and bile acid metabolism that ameliorates multiple features of metabolic syndrome. Targeting extraoral bitter taste receptors may be useful in metabolic disease. Keywords: Bitter taste receptor, Diabetes, Enteroendocrine hormones, GLP-1, Intestinal signaling, Isohumulone

Abstract In this paper, we prove the following result: Let f be a nonconstant meromorphic function of finite order, p be a nonconstant polynomial, and c be a nonzero constant. If f, Δcf $\Delta _{c}f$, and Δcnf $\Delta_{c}^{n}f$ ( n≥2 $n\ge 2$) share ∞ and p CM, then f≡Δcf $f\equiv \Delta_{c}f$. Our result provides a difference analogue of the result of Chang and Fang in 2004 (Complex Var. Theory Appl. 49(12):871–895, 2004).

The human gut microbiome (GM) in healthy people is chronically exposed to tetracycline (TET) via environmental exposure and dietary uptake. However, limited information is available on its effect on the GM metabolome and effect on the host, especially at the dietary exposure level. Here, we investigated how TET at both sub-pharmaceutical and dietary exposure levels affects the metabolome and the secretome-induced host immune response by studying several representative gut bacteria. Interestingly, the metabolome showed a highly species-specific pattern with a distinct dose-response relationship. B. fragilis was highly sensitive to TET and vitamin, nucleotide, and amino acid metabolism pathways were the most vulnerable metabolic pathways at dietary exposure level. For key metabolite short chain fatty acids, TET significantly induced the synthesis of butyrate in B. fragilis, rather than C. sporogenes and E. coli. Furthermore, TET induced the release of lipopolysaccharides (LPS) in E. coli and enhanced the immune response; however, there was no obvious effect on B. fragilis. Interestingly, the overall immune response modulation with TET exposure relied on the ratio between E. coli and B. fragilis, possibly due to the neutralization of active LPS from E. coli by the LPS from B. fragilis. Overall, our results showed that the effect of TET from environmental exposure on the host health would be highly dependent on the GM composition, especially for the gut bacterial metabolome and secretome induced immune response. Keywords: Gut bacteria, Tetracycline, Metabolism, Immune response

We prove a unicity theorem of entire functions that share two distinct small functions with their shifts. The corollary of the theorem confirms the conjecture posed by Li and Gao (2011).

We prove that if f is a transcendental meromorphic function of finite order and ∑a≠∞δ(a,f)+δ(∞,f)=2, then K(f(k))=2k(1−δ(∞,f))1+k−kδ(∞,f), where K(f(k))=limr→∞N(r,1/f(k))+N(r,f(k))T(r,f(k)) This result improves a result by Singh and Kulkarni.

We prove a difference analogue of the celebrated Tumura--Hayman--Clunie theorem. Let f be a transcendental entire function, let c be a nonzero constant and let n be a positive integer. If f and Δcn f omit zero in the whole complex plane, then either f (z) = exp(h1(z) + C1z), where h1 is an entire function of period c and exp(C1c) ≠ 1, or f (z) = exp(h2(z) + C2z), where h2 is an entire function of period 2c and C2 satisfies (1 + exp(C2c) /1- exp(C2c) 2n = 1. [ABSTRACT FROM AUTHOR]

In this paper, we study the unicity of meromorphic functions and their differential-difference polynomials. Our results improve some results due to Chen-Yi [Results Math 63 (2013):557-565], Chen-Xu [Open Math 18 (2020):211-215], Banerjee-Maity [Bull Korean Math Soc 58 (2021):1175-1192], and Narasimha-Shilpa [Adv Pure Appl Math 13 (2022):53-61] [ABSTRACT FROM AUTHOR]