A green edge-hosted zinc single-site heterogeneous catalyst for superior Fenton-like activity.

Developing green heterogeneous catalysts with excellent Fenton-like activity is critical for water remediation technologies. However, current catalysts often rely on toxic transitional metals, and their catalytic performance is far from satisfactory as alternatives of homogeneous Fenton-like catalysts. In this study, a green catalyst based on Zn single-atom was prepared in an ammonium atmosphere using ZIF-8 as a precursor. Multiple characterization analyses provided evidence that abundant intrinsic defects due to the edge sites were created, leading to the formation of a thermally stable edge-hosted Zn-N4 single-atom catalyst (ZnN4-Edge). Density functional theory calculations revealed that the edge sites equipped the single-atom Zn with a super catalytic performance, which not only promoted decomposition of peroxide molecule (HSO5-) but also greatly lowered the activation barrier for •OH generation. Consequently, the as-prepared ZnN4-Edge exhibited extremely high Fenton-like performance in oxidation and mineralization of phenol as a representative organic contaminant in a wide range of pH, realizing its quick detoxification. The atom-utilization efficiency of the ZnN4-Edge was ~104 higher than an equivalent amount of the control sample without edge sites (ZnN4), and the turnover frequency was ~103 times of the typical benchmark of homogeneous catalyst (Co2+). This study opens up a revolutionary way to rationally design and optimize heterogeneous catalysts to homogeneous catalytic performance for Fenton-like application.

CD160 Signaling Is Essential for CD8+ T Cell Memory Formation via Upregulation of 4-1BB.

A better understanding of the regulatory mechanisms governing the development of memory CD8+ T cells could provide instructive insights into vaccination strategies and T cell-based immunotherapies. In this article, we showed that CD160 surface protein is required for CD8+ T cell memory formation. In the response to acute lymphocytic choriomeningitis virus infection in a mouse model, CD160 ablation resulted in the failure of the development of all three memory CD8+ T cell subsets (central, effective, and tissue-resident memory), concomitant with a skewed differentiation into short-lived effector T cells. Such memory-related defect was manifested by a diminished protection from viral rechallenge. Mechanistically, CD160 deficiency led to downregulation of 4-1BB in activated CD8+ T cells, which contributes to the impaired cell survival and decreased respiratory capacity. The nexus between CD160 and 4-1BB was substantiated by the observation that ectopic introduction of 4-1BB was able to largely complement the loss of CD160 in memory CD8+ T cell development. Collectively, our studies discovered that CD160, once thought to be a coinhibitor of T cell signaling, is an essential promoter of memory CD8+ T cell development via activation of the costimulatory molecule 4-1BB.

The genetic landscape of histologically transformed marginal zone lymphomas.

BACKGROUND: Marginal zone lymphomas (MZLs) comprise a diverse group of indolent lymphoproliferative disorders; however, some patients develop histologic transformation (HT) with rapid progression to aggressive lymphoma. METHODS: Forty-three MZLs with HT (HT-MZLs), 535 MZLs, and 174 de novo diffuse large B-cell lymphomas (DLBCLs) without rearrangements of MYC, BCL2, and BCL6 were collected. Among these, 22 HT-MZLs, 39 MZLs, and 174 DLBCLs were subjected to 148-gene targeted exome sequencing. The clinicopathologic features of patients who had HT-MZL and their genetic alterations were compared with those of patients who had MZLs and DLBCLs. RESULTS: All 43 HT-MZLs corresponded to DLBCLs. No HT-MZLs harbored BCL2 and MYC and/or BCL6 rearrangements. Bone marrow involvement and higher levels of lactate dehydrogenase were significantly more common in HT-MZLs than in MZLs. Furthermore, upregulated BCL6, MUM1, C-MYC, and Ki-67 expression was observed more frequently in HT-MZLs than in MZLs. TBL1XR1 was the most frequently altered gene (63.6%) in HT-MZLs, followed by CCND3 (31.8%), CARD11, ID3, and TP53 (22.7%). A trend toward worse progression-free survival in patients with TBL1XR1 mutations was observed. Compared with MZLs and non-germinal center B-cell (GCB) type DLBCLs, significantly higher frequencies of TBL1XR1 and ID3 mutations were identified in HT-MZLs. PIM1 mutations frequently occurred in DLBCLs and were significantly associated with TBL1XR1 mutations but were mutated less in HT-MZLs that had TBL1XR1 mutations. CONCLUSIONS: The current findings reveal the clinicopathologic and genetic features of HT-MZLs, suggesting that these tumors might constitute a group distinct from MZL and de novo non-GCB type DLBCL. TBL1XR1 mutations may be considered a predictor of HT in MZL.

Insights into the Enhanced Bioavailability of Per- and Polyfluoroalkyl Substances in Food Caused by Chronic Inflammatory Bowel Disease.

Understanding the bioavailability of per- and polyfluoroalkyl substances (PFAS) in food is essential for accurate human health risk assessment. Given the rising incidence of inflammatory bowel disease (IBD), this study aimed to investigate the impacts of IBD on the bioavailability of PFAS in food using mice models. The relative bioavailability (RBA) of PFAS was the highest in the chronic IBD mice (64.3-144%), followed by the healthy (60.8-133%) and acute IBD mice (41.5-121%), suggesting that chronic IBD enhanced the PFAS exposure risk. In vitro tests showed that the intestinal micelle stability increased as a result of reduced content of short-chain fatty acids, thus promoting the PFAS bioaccessibility in the digestive fluid of chronic IBD. Additionally, increased pathogenic and decreased beneficial bacteria in the gut of IBD groups facilitated the intestinal permeability, thus enhancing PFAS absorption. These together explained the higher RBA of PFAS in the chronic IBD. However, remarkably lower enzymatic activities suggested severely impaired digestive ability in the acute IBD, which facilitated the excretion of PFAS from feces, thus lowering the RBA. Conversely, PFAS exposure might exacerbate IBD by changing the gut microbiota structures. This study hints that individuals with chronic intestinal inflammation might have higher PFAS exposure risk than the healthy population.

Integration of Nontarget Screening and QSPR Models to Identify Novel Organophosphate Esters of High Priority in Aquatic Environment.

With the development of large numbers of novel organophosphate esters (OPEs) alternatives, it is imperative to screen and identify those with high priority. In this study, surface water, biofilms, and freshwater snails were collected from the flow-in rivers of Taihu Lake Basin, China. Screened by target, suspect, and nontarget analysis, 11 traditional and 14 novel OPEs were identified, of which 5 OPEs were first discovered in Taihu Lake Basin. The OPE concentrations in surface water ranged from 196 to 2568 ng/L, with the primary homologue tris(2,4-ditert-butylphenyl) phosphate (TDtBPP) being newly identified, which was likely derived from the transformation of tris(2,4-ditert-butylphenyl) phosphite. The majority of the newly identified OPEs displayed substantially higher bioaccumulation and biomagnification potentials in the biofilm-snail food chain than the traditional ones. Quantitative structure-property relationship models revealed both hydrophobicity and polarity influenced the bioaccumulation and biomagnification of the OPEs, while electrostatic attraction also had a contribution to the bioaccumulation in the biofilm. TDtBPP was determined as the utmost priority by toxicological priority index scheme, which integrated concentration, bioaccumulation, biomagnification, acute toxicity, and endocrine disrupting potential of the identified OPEs. These findings provide novel insights into the behaviors of OPEs and scientific bases for better management of high-risk pollutants in aquatic ecosystem.

Contribution of Continued Dermal Exposure of PFAS-Containing Sunscreens to Internal Exposure: Extrapolation from In Vitro and In Vivo Tests to Physiologically Based Toxicokinetic Models.

Per- and polyfluoroalkyl substances (PFASs) are widely present in sunscreen products as either active ingredients or impurities. They may penetrate the human skin barrier and then pose potential health risks. Herein, we aimed to develop a physiologically based toxicokinetic (PBTK) model capable of predicting the body loading of PFASs after repeated, long-term dermal application of commercial sunscreens. Ten laboratory-prepared sunscreens, generally falling into two categories of water-in-oil (W/O) and oil-in-water (O/W) sunscreens, were subject to in vitro percutaneous penetration test to assess the impacts of four sunscreen ingredients on PFAS penetration. According to the results, two sunscreen formulas representing W/O and O/W types that mostly enhanced PFAS dermal absorption were then selected for a subsequent 30 day in vivo exposure experiment in mice. PBTK models were successfully established based on the time-dependent PFAS concentrations in mouse tissues (R2 = 0.885-0.947) and validated through another 30 day repeated exposure experiment in mice using two commercially available sunscreens containing PFASs (R2 = 0.809-0.835). The PBTK model results suggest that applying sunscreen of the same amount on a larger skin area is more conducive to PFAS permeation, thus enhancing the exposure risk. This emphasizes the need for caution in practical sunscreen application scenarios, particularly during the summer months.

Screening Novel Per- and Polyfluoroalkyl Substances in Human Blood Based on Nontarget Analysis and Underestimated Potential Health Risks.

Nontarget analysis has gained prominence in screening novel perfluoroalkyl and polyfluoroalkyl substances (PFASs) in the environment, yet remaining limited in human biological matrices. In this study, 155 whole blood samples were collected from the general population in Shijiazhuang City, China. By nontarget analysis, 31 legacy and novel PFASs were assigned with the confidence level of 3 or above. For the first time, 11 PFASs were identified in human blood, including C1 and C3 perfluoroalkyl sulfonic acids (PFSAs), C4 ether PFSA, C8 ether perfluoroalkyl carboxylic acid (ether PFCA), C4-5 unsaturated perfluoroalkyl alcohols, C9-10 carboxylic acid-perfluoroalkyl sulfonamides (CA-PFSMs), and C1 perfluoroalkyl sulfonamide. It is surprising that the targeted PFASs were the highest in the suburban population which was impacted by industrial emission, while the novel PFASs identified by nontarget analysis, such as C1 PFSA and C9-11 CA-PFSMs, were the highest in the rural population who often drank contaminated groundwater. Combining the toxicity prediction results of the bioaccumulation potential, lethality to rats, and binding affinity to target proteins, C3 PFSA, C4 and C7 ether PFSAs, and C9-11 CA-PFSMs exhibit great health risks. These findings emphasize the necessity of broadening nontarget analysis in assessing the PFAS exposure risks, particularly in rural populations.

Structure-Related Thyroid Disrupting Effect of Perfluorooctanesulfonate-like Substances in Zebrafish Larvae.

Chlorinated polyfluorooctane ether sulfonate (6:2 Cl-PFESA), hydrogenated polyfluorooctane ether sulfonate (6:2 H-PFESA), and chlorinated polyfluorooctanesulfonate (Cl-PFOS) share structural similarities with the regulated perfluorooctanesulfonate (PFOS), but their toxic potential is rarely known. Here, the thyroid disrupting potential of these four compounds in zebrafish larvae has been comparably investigated. PFOS, Cl-PFOS, and 6:2 Cl-PFESA were accumulated in the larvae at similar levels, approximately 1.3-1.6 times higher than 6:2 H-PFESA. Additionally, PFOS, Cl-PFOS, and 6:2 Cl-PFESA exhibited stronger disruption than 6:2 H-PFESA on genetic regulation, particularly concerning thyroid hormone (TH) activation and action and on TH homeostasis in both free and total forms of thyroxine (T4) and 3,5,3'-triiodothyronine (T3). These results indicate that chlorination or oxygen insertion does not substantially alter the thyrotoxicity of PFOS, but hydrogenation mitigates it. Molecular docking analysis and the luciferase reporter gene assay provided mechanistic perspectives that the PFOS-like substances could competitively replace THs to bind with TH plasma and membrane transporters, thereby disrupting TH transport and action, respectively. Moreover, they are also potent to disrupt TH synthesis and activation through Na+/K+-dependent transport of I- or competitive binding to the sites of deiodinases.

Masks As a New Hotspot for Antibiotic Resistance Gene Spread: Reveal the Contribution of Atmospheric Pollutants and Potential Risks.

The consumption of disposable surgical masks (DSMs) considerably increased during the coronavirus pandemic in 2019. Herein, we explored the spread of antibiotic resistance genes (ARGs) and the potential risks of antibiotic resistant bacteria (ARB) on DSMs. At environmentally relevant concentrations, the conjugate transfer frequency (CTF) of ARGs increased by 1.34-2.37 folds by 20 µg/m3 of atmospheric water-soluble inorganic ions (WSIIs), and it increased by 2.62-2.86 folds by 80 ng/m3 of polycyclic aromatic hydrocarbons (PAHs). Total suspended particulates (TSP) further promoted the CTF in combination with WSIIs or PAHs. Under WSII and PAH exposure, gene expression levels related to oxidative stress, cell membrane, and the adenosine triphosphate (ATP) were upregulated. WSIIs predominantly induced cellular contact, while PAHs triggered ATP formation and membrane damage. Molecular dynamics simulations showed that WSIIs and PAHs reduced membrane lipid fluidity and increased membrane permeability through interactions with the phosphatidylcholine bilayer. DSM filtering performance decreased, and the CTF of ARGs increased with the wearing time. The gut simulator test showed that ARB disrupted the human gut microbial community and increased total ARG abundance but did not change the ARG abundance carried by ARB themselves. A mathematical model showed that long-term WSII and PAH exposure accelerated ARG dissemination in DSMs.

Multimedia and Full-Life-Cycle Monitoring Discloses the Dynamic Accumulation Rules of PFAS and Underestimated Foliar Uptake in Wheat near a Fluorochemical Industrial Park.

The escalating concern of perfluoroalkyl and polyfluoroalkyl substances (PFAS), particularly at contaminated sites, has prompted extensive investigations. In this study, samples of multimedia including air, rhizosphere soil, and tissues of wheat at various growing stages were collected near a mega fluorochemical industrial park in China. Perfluorooctanoic acid (PFOA) was predominant in both air and soil with a strong correlation, highlighting air deposition as an important source in the terrestrial system. PFAS concentrations in wheat decreased in the stem and ear but increased in the leaves as wheat matured. Specifically, perfluorobutanoic acid (PFBA) dominated in the aboveground tissues in the full-life-cycle, except that PFOA surpassed and became predominant in leaves during the filling and maturing stages, hinting at an airborne source. For all PFAS, both bioaccumulation factors and translocation factors (TFs) were inversely correlated with the carbon chain length during the full-life-cycle. The obtained TF values were considerably higher than those obtained from ambient sites reported previously, further suggesting an unneglectable foliar uptake from air, which was estimated to be 25% for PFOA. Moreover, spray irrigation remarkably enhanced the absorption of PFAS in wheat via foliar uptake relative to flood irrigation. The estimated daily intake of PFBA via wheat consumption and air inhalation was 0.50 µg/kg/day for local residents, at least one magnitude higher than the corresponding threshold, suggesting an alarmingly high exposure risk.

Identification of Primary Organophosphate Esters Contributing to Enhanced Risk of Gestational Diabetes Mellitus Based on a Case-Control Study.

Epidemiological studies on associations of organophosphate ester (OPE) exposure and gestational diabetes mellitus (GDM) risk, which remain rare and inconclusive, were carried out with a case-control population comprising 287 GDM and 313 non-GDM pregnant women recruited from Tianjin. The GDM group suffered distinctly higher serum concentrations of tri-n-butyl phosphate (TNBP), tri(2-butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPHP), tri-iso-propyl phosphate (TIPP), and tri(1-chloro-2-propyl) phosphate (TCIPP) than the healthy control group (p < 0.001). Traditional analysis methods employed for either individual or mixture effects found positive correlations (p < 0.05) between the concentrations of five OPEs (i.e., TNBP, TBOEP, TPHP, TIPP, and TCIPP) and the incidence of GDM, while 2-ethylhexyl diphenyl phosphate, tri(1-chloro-2-propyl) phosphate, and bis(2-ethylhexyl) phosphate exhibited opposite effects. Three machine learning methods considering the concurrence of OPE mixture exposure and population characteristics were applied to clarify their relative importance to GDM risk, among which random forest performed the best. Several OPEs, particularly TNBP and TBOEP ranking at the top, made greater contributions than some demographical characteristics, such as prepregnancy body mass index and family history of diabetes, to the occurrence of GDM. This was further validated by another independent case-control population obtained from Hangzhou.

Complexation with Metal Ions Affects Chlorination Reactivity of Dissolved Organic Matter: Structural Reactomics of Emerging Disinfection Byproducts.

Metal ions are liable to form metal-dissolved organic matter [dissolved organic matter (DOM)] complexes, changing the chemistry and chlorine reactivity of DOM. Herein, the impacts of iron and zinc ions (Fe3+ and Zn2+) on the formation of unknown chlorinated disinfection byproducts (Cl-DBPs) were investigated in a chlorination system. Fe3+ preferentially complexed with hydroxyl and carboxyl functional groups, while Zn2+ favored the amine functional groups in DOM. As a consequence, electron-rich reaction centers were created by the C-O-metal bonding bridge, which facilitated the electrophilic attack of α-C in metal-DOM complexes. Size-reactivity continuum networks were constructed in the chlorination system, revealing that highly aromatic small molecules were generated during the oxidation and decarbonization of metal-DOM complexes. Molecular transformation related to C-R (R represents complex sites) loss was promoted via metal complexation, including decarboxylation and deamination. Consequently, complexation with Fe3+ and Zn2+ promoted hydroxylation by the C-O-metal bonding bridge, thereby increasing the abundances of unknown polychlorinated Cl-DBPs by 9.6 and 14.2%, respectively. The study provides new insights into the regulation of DOM chemistry and chlorine reactivity by metal ions in chlorination systems, emphasizing that metals increase the potential health risks of drinking water and more scientific control standards for metals are needed.

Characterization of the Bioavailability of Per- and Polyfluoroalkyl Substances in Farmland Soils and the Factors Impacting Their Translocation to Edible Plant Tissues.

In this study, various crops and farmland soils were collected from the Fen-Wei Plain, China, to investigate the bioavailability of perfluoroalkyl substances (PFAS), their accumulation in edible plant tissues, and the factors impacting their accumulation. PFAS were frequently detected in all of the crops, with total concentrations ranging from 0.61 to 35.8 ng/g. The results of sequential extractions with water, basic methanol, and acidic methanol indicate that water extraction enables to characterize the bioavailability of PFAS in soil to edible plant tissues more accurately, especially for the shorter-chain homologues. The bioavailability of PFAS was remarkably enhanced in the rhizosphere (RS) soil, with the strongest effect observed for leafy vegetables. The water-extracted Σ16PFAS in RS soil was strongly correlated with the content of dissolved organic carbon in the soil. Tannins and lignin, identified as the main components of plant root exudates by Fourier transform-ion cyclotron resonance mass spectrometry, were found to enhance the bioavailability of PFAS significantly. Redundancy analysis provided strong evidence that the lipid and protein contents in edible plant tissues play important roles in the accumulation of short- and long-chain PFAS, respectively. Additionally, the high water demand of these tissues during the growth stage greatly facilitated the translocation of PFAS, particularly for the short-chain homologues and perfluorooctanoic acid.

Stability and Biotransformation of 6:2 Fluorotelomer Sulfonic Acid, Sulfonamide Amine Oxide, and Sulfonamide Alkylbetaine in Aerobic Sludge.

The 6:2 fluorotelomer sulfonamide (6:2 FTSAm)-based compounds signify a prominent group of per- and polyfluoroalkyl substances (PFAS) widely used in contemporary aqueous film-forming foam (AFFF) formulations. Despite their widespread presence, the biotransformation behavior of these compounds in wastewater treatment plants remains uncertain. This study investigated the biotransformation of 6:2 FTSAm-based amine oxide (6:2 FTNO), alkylbetaine (6:2 FTAB), and 6:2 fluorotelomer sulfonic acid (6:2 FTSA) in aerobic sludge over a 100-day incubation period. The biotransformation of 6:2 fluorotelomer sulfonamide alkylamine (6:2 FTAA), a primary intermediate product of 6:2 FTNO, was indirectly assessed. Their stability was ranked based on the estimated half-lives (t1/2): 6:2 FTAB (no obvious products were detected) ≫ 6:2 FTSA (t1/2 ≈28.8 days) > 6:2 FTAA (t1/2 ≈11.5 days) > 6:2 FTNO (t1/2 ≈1.2 days). Seven transformation products of 6:2 FTSA and 15 products of 6:2 FTNO were identified through nontarget and suspect screening using high-resolution mass spectrometry. The transformation pathways of 6:2 FTNO and 6:2 FTSA in aerobic sludge were proposed. Interestingly, 6:2 FTSAm was hardly hydrolyzed to 6:2 FTSA and further biotransformed to perfluoroalkyl carboxylic acids (PFCAs). Furthermore, the novel pathways for the generation of perfluoroheptanoic acid (PFHpA) from 6:2 FTSA were revealed.

Novel Insights into the Promoted Accumulation of Nitro-Polycyclic Aromatic Hydrocarbons in the Roots of Legume Plants.

Substituted polycyclic aromatic hydrocarbons (sub-PAHs) are receiving increased attention due to their high toxicity and ubiquitous presence. However, the accumulation behaviors of sub-PAHs in crop roots remain unclear. In this study, the accumulation mechanism of sub-PAHs in crop roots was systematically disclosed by hydroponic experiments from the perspectives of utilization, uptake, and elimination. The obtained results showed an interesting phenomenon that despite not having the strongest hydrophobicity among the five sub-PAHs, nitro-PAHs (including 9-nitroanthracene and 1-nitropyrene) displayed the strongest accumulation potential in the roots of legume plants, including mung bean and soybean. The nitrogen-deficient experiments, inhibitor experiments, and transcriptomics analysis reveal that nitro-PAHs could be utilized by legumes as a nitrogen source, thus being significantly absorbed by active transport, which relies on amino acid transporters driven by H+-ATPase. Molecular docking simulation further demonstrates that the nitro group is a significant determinant of interaction with an amino acid transporter. Moreover, the depuration experiments indicate that the nitro-PAHs may enter the root cells, further slowing their elimination rates and enhancing the accumulation potential in legume roots. Our results shed light on a previously unappreciated mechanism for root accumulation of sub-PAHs, which may affect their biogeochemical processes in soils.

Macrophages regulate healing-associated fibroblasts in diabetic wound.

BACKGROUND: Recovery from a foot ulcer is compromised in a diabetic status, due to the impaired tissue microenvironment that consists of altered inflammation, angiogenesis and fibrosis. Phenotypic alterations in both macrophages and fibroblasts have been detected in the diabetic wound. Recently, a fibroblast subpopulation that expresses high matrix metalloproteinase 1 (MMP1), MMP3, MMP11 and Chitinase-3-Like Protein 1 (CHI3L1) was associated with a successful diabetic wound healing. However, it is not known whether these healing-associated fibroblasts are regulated by macrophages. METHODS AND RESULTS: We used bioinformatic tools to analyze selected public databases on normal and diabetic skin from patients, and identified genes significantly altered in diabetes. In a mouse model for diabetic wound healing, we detected not only a loss of the spatiotemporal changes in interleukin 1ß (IL1ß), IL6, IL10 and vascular endothelial growth factor A (VEGF-A) in wound macrophages, but also a compromised expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in healing-associated wound fibroblasts in a diabetic status. Co-culture with diabetic macrophages significantly reduced the expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in fibroblasts from non-diabetic wound. Co-culture with non-diabetic macrophages or diabetic macrophages supplied with IL6 significantly increased the expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in fibroblasts from diabetic wound. Moreover, macrophage-specific expression of IL6 significantly improved wound healing and angiogenesis in diabetic mice. CONCLUSIONS: Macrophages may induce the activation of wound-healing-associated fibroblasts, while the defective macrophages in diabetes may be corrected with IL6 treatment as a promising therapy for diabetic foot disease.

Role of diet in the risks of esophageal adenocarcinoma and squamous cell carcinoma: an updated umbrella review.

PURPOSE: This updated umbrella review aimed to evaluate the evidence regarding the associations between dietary factors and the risks of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify relevant studies. The quality of the included meta-analyses was evaluated using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2). For each association, the number of cases, random effects pooled effect size, 95% confidence intervals (CIs), heterogeneity, 95% prediction interval (PrI), small-study effect, and excess significance bias were recalculated to determine the evidence level. RESULTS: We identified 33 meta-analyses describing 58 dietary factors associated with ESCC and 29 meta-analyses describing 38 dietary factors associated with EAC. There was convincing evidence regarding the association of 2 dietary factors (areca nut and high alcohol) with the risk of ESCC. There was highly suggestive evidence regarding the association of only 1 dietary factor (healthy pattern) with the risk of ESCC. There was suggestive evidence regarding the association of 11 dietary factors with the risk of ESCC, including fruit, citrus fruit, vegetables, pickled vegetables, maté tea, moderate alcohol, hot beverages and foods, hot tea, salt, folate, and vitamin B6. There was convincing evidence regarding the association of one dietary factor (vitamin B6) with the risk of EAC. There was suggestive evidence regarding the association of 4 dietary factors with the risk of EAC, including processed meat, dietary fibre, carbohydrate, and vitamin B12. The convincing evidence regarding the associations between dietary factors and the risks of ESCC and EAC remained robust in sensitivity analyses. CONCLUSIONS: This umbrella review highlighted convincing evidence regarding the associations of areca nut and high alcohol with a higher risk of ESCC. Additionally, an association between vitamin B6 and a decreased risk of EAC was observed. Further research is needed to examine the dietary factors with weak evidence regarding their associations with ESCC and EAC.

Elucidating the toxicity mechanisms of organophosphate esters by adverse outcome pathway network.

With the widespread use of organophosphate esters (OPEs), the accumulation and toxicity effect of OPEs in biota are attracting more and more concern. In order to clarify the mechanism of toxicity of OPEs to organisms, this study reviewed the OPEs toxicity and systematically identified the mechanism of OPEs toxicity under the framework of adverse outcome pathway (AOP). OPEs were divided into three groups (alkyl-OPEs, aryl-OPEs, and halogenated-OPEs) and biota was divided into aquatic organism and mammals. The results showed that tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) mainly caused neurotoxicity, reproductive, and hepatotoxicity in different mechanisms. According to the constructed AOP network, the toxicity mechanism of OPEs on aquatic organisms and mammals is different, which is mainly attributed to the different biological metabolic systems of aquatic organisms and mammals. Interestingly, our results indicate that the toxicity effect of the three kinds of OPEs on aquatic organisms is different, while there was no obvious difference in the mechanism of toxicity of OPEs on mammals. This study provides a theoretical basis for OPEs risk assessment in the future.

Physiologically based toxicokinetic modelling of Tri(2-chloroethyl) phosphate (TCEP) in mice accounting for multiple exposure routes.

Exposure routes are important for health risk assessment of chemical risks. The application of physiologically based toxicokinetic (PBTK) models to predict concentrations in vivo can determine the effects of harmful substances and tissue accumulation on the premise of saving experimental costs. In this study, Tri(2-chloroethyl) phosphate (TCEP), an organophosphate ester (OPE), was used as an example to study the PBTK model of mice exposed to different exposure doses by multiple routes. Different routes of exposure (gavage and intradermal injection) can cause differences in the concentration of chemicals in the organs. TCEP that enters the body through the mouth is mainly concentrated in the gastrointestinal tract and liver. However, the concentrations of chemicals that enter the skin into the mice are higher in skin, rest of body, and blood. In addition, TCEP was absorbed and accumulated very rapidly in mice, within half an hour after a single exposure. We have successfully established a mouse PBTK model of the TCEP accounting for multiple exposure Routes and obtained a series of kinetic parameters. The model includes blood, liver, kidney, stomach, intestine, skin, and rest of body compartments. Oral and dermal exposure route was considered for PBTK model. The PBTK model established in this study has a good predictive ability. More than 70% of the predicted values deviated from the measured values by less than 5-fold. In addition, we extrapolated the model to humans. A human PBTK model is built. We performed a health risk assessment for world populations based on human PBTK model. The risk of TCEP in dust is greater through mouth than through skin. The risk of TCEP in food of Chinese population is greater than dust.

Association of Body Mass Index and the Risk of Gastro-Esophageal Cancer: A Mendelian Randomization Study in a Japanese Population.

There are growing concerns that body mass index (BMI) is related to cancer risk at various anatomical sites, including the upper gastrointestinal tract, and the existence of a causal relationship remains unclear. The Mendelian randomization (MR) method uses instrumental genetic variables of risk factors to explore whether a causal relationship exists while preventing confounding. In our study, genome-wide association study (GWAS) data from the BioBank Japan (BBJ) project were used. Genetic variants were chosen as instrumental variables using inverse-variance weighting (IVW), MR-Egger regression and weighted-median methods to estimate the causal relationship between BMI and the risk of gastro-esophageal cancer. We found no evidence to support a causal association between BMI and risk of gastric cancer [odds ratio (OR) =0.99 per standard deviation (SD) increase in BMI; 95% confidence interval (CI): (0.76-1.30); P = 0.96] or esophageal cancer [0.78(0.50-1.22); P = 0.28] using the IVW method. Sensitivity analysis did not reveal any sign of horizontal pleiotropy. Additionally, in the gender-stratified analysis, no causal association was found. Findings from this study do not support a causal effect of BMI on gastro-esophageal cancer risk. However, we cannot rule out a modest or nonlinear effect of BMI.