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Objective: Dichlorodiphenyldichloroethylene (DDE), an obesogen accumulating in adipose tissue, is released into circulation with weight loss, although its impact is underexplored among adolescents. We tested the association using an integrative translational approach of epidemiological analysis among adolescents with obesity and in vitro measures exploring the impact of DDE on adipogenesis via preadipocytes., Methods: We included 63 participants from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort. We assessed 4,4'-DDE in visceral adipose tissue at surgery and BMI and waist circumference at surgery and 0.5, 1, 3, and 5 years after. We conducted longitudinal analysis to estimate the interaction on weight loss between DDE and time since surgery. In vitro analysis quantified adipogenic differentiation in commercial human preadipocytes exposed to 4,4'-DDE via fluorescent staining and imaging., Results: A dose-response relationship was observed, with the low-exposure group having a greater reduction in BMI during the first year compared to higher-exposure groups and showing smaller regains compared to higher-exposure groups after the first year. In vitro analysis of preadipocytes treated with 4,4'-DDE during adipogenic differentiation for 12 days showed a concentration-dependent increase in lipid accumulation., Conclusions: DDE could contribute to weight trajectory among adolescents undergoing bariatric surgery, potentially mediated via promoted adipogenesis in preadipocytes., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Background: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family., Methods: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58 hep-/- . The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS)., Results: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m 6 A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m 6 A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis., Conclusions: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m 6 A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury., (© 2024. The Author(s).)

In 2021, 53 countries conducted indoor residual spraying (IRS), the application of insecticides such as dichlorodiphenyl trichloroethane (DDT) or pyrethroids to the walls of homes to control malaria. Animal studies show that these insecticides can increase susceptibility to infections but only one human study was conducted in a population from an area where IRS is applied. The aim of the present study was thus to investigate whether maternal exposure to DDT, its breakdown product dichlorodiphenyl dichloroethylene (DDE) or pyrethroid insecticides is associated with symptoms of infection among children living in a region of South Africa were IRS is conducted annually. As part of the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) we measured maternal serum concentrations of DDT and DDE, and urinary concentrations of four pyrethroid metabolites in peripartum samples. Poisson regression models with robust variance estimates were used to investigate associations with the rates of infection symptoms between ages 3.5-5 years among 629 children as assessed based on caregiver interviews. Multiple pyrethroid metabolites were associated with infection symptoms. For instance, cis-DBCA was associated with increased rates of ear infection (Incidence Rate Ratio for a 10-fold increase (IRR 10 ) = 1.4; 95 % Confidence Interval (CI) = 1.0, 2.1) and persistent diarrhea (IRR 10  = 2.1; 95 % CI = 1.2, 3.9), trans-DCCA was associated with increased rates of colds in children (IRR 10  = 1.3; 95 % CI = 1.0, 1.6) and persistent fever (IRS 10  = 1.4; 95 % CI = 1.0, 2.0), and 3-PBA was associated with increased rates of persistent fever (IRR 10  = 1.8; 95 % CI = 1.0, 3.0). We found limited evidence of association between maternal DDE and DDT serum concentrations and infection symptoms. Results suggest that prenatal exposure to pyrethroid insecticides may be associated with infections among children from an area where IRS is conducted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Dichlorodiphenyltrichloroethane (DDT) is well known for its harmful effects and has been officially banned as a pesticide around the world. However, DDT pollution still exists in natural environments in China because DDT degrade very slowly. In this study, 60 soil samples were collected from Cixi, Zhejiang Province, and the levels of DDTs and its metabolites in soil and health risks were investigated. The results showed that the detection rate of DDT in soil samples were 100%, and the total DDTs residue in soil ranged from 0.007 to 1.208 mg/kg, with an average of 0. 113±0. 035 mg/kg, which exceeded the second-level Chinese soil environmental quality standard for farmland soil. The average residuals of p,p'-DDT, p,p'-DDE (dichlorodiphenyldichloroethylene), p,p'-DDD (dichlorodiphenyldichloroethane) and o,p'-DDT accounted for 34.8%, 50.9%, 8.0% and 6.3% of the total DDTs, respectively. The DDD/DDE ratios indicated a dehydrochlorination of DDT to DDE under aerobic conditions at most sampling sites. The ratios of (p,p'-DDE+p,p'-DDD)/p,p'-DDT and o,p'-DDT/p,p'-DDT indicating the DDT in the field were mainly introduced via industrial DDT and dicofol, including historical residue and fresh input. The health risk assessment showed that DDT-contaminated sites do not pose a non-carcinogenic risk to humans, and pose a very low risk of cancer to children and a low risk of cancer to adults. Overall, this study helps to understand the distribution, sources and health risks of DDT in typical soils.

Acute myeloid leukemia (AML) is a rare malignancy representing 15-20% of all leukemia diagnoses among children. Maternal exposure to persistent organic pollutants is suggestive of increased risk for childhood AML based on existing evidence. We aimed to evaluate the relationship between persistent organic pollutants and childhood AML using newborn dried bloodspots (DBS) from the Michigan BioTrust for Health. We obtained data on AML cases diagnosed prior to 15 years of age (n = 130) and controls (n = 130) matched to cases on week of birth from the Michigan Department of Health and Human Services. We quantified levels of dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), and polybrominated diphenyl ether congener 47 (BDE-47) in newborn DBS. We also evaluated other organochlorine pesticides, polychlorinated biphenyls, polybrominated biphenyl congener 153, and polybrominated diphenyl ethers, though these were not further evaluated as >60% of observations were above the limit of detection for these chemicals. To evaluate the association between each chemical and AML, we used multivariable conditional logistic regression. In our multivariable model of HCB adjusted for month of birth, maternal age at delivery, and area poverty, we observed no association with AML (Odds Ratio [OR] per interquartile range increase: 1.17, 95% CI: 0.80, 1.69). For p,p'-DDE, ORs were significantly lower for those exposed to the highest tertile of p,'p-DDE (≥0.29 pg/mL, OR: 0.32, 95% CI: 0.11, 0.95) compared to the first tertile (<0.09 pg/mL). We observed no statistically significant associations between HCB and BDE-47 and AML. We observed a reduced odds of exposure to p,'p-DDE and an increased, though imprecise, odds of exposure to HCB among AML cases compared to controls. Future studies would benefit from a larger sample of AML patients and pooling newborn DBS across multiple states to allow for additional variability in exposures and evaluation of AML subtypes, which may have differing etiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Clinicians often lack the necessary expertise to differentially diagnose multiple underlying rare diseases (RDs) due to their complex and overlapping clinical features, leading to misdiagnoses and delayed treatments. The aim of this study is to develop a novel electronic differential diagnostic support system for RDs., Method: Through integrating two Bayesian diagnostic methods, a candidate list was generated with enhance clinical interpretability for the further Q&A based differential diagnosis (DDX). To achieve an efficient Q&A dialogue strategy, we introduce a novel metric named the adaptive information gain and Gini index (AIGGI) to evaluate the expected gain of interrogated phenotypes within real-time diagnostic states., Results: This DDX tool called RDmaster has been implemented as a web-based platform (http://rdmaster.nbscn.org/). A diagnostic trial involving 238 published RD patients revealed that RDmaster outperformed existing RD diagnostic tools, as well as ChatGPT, and was shown to enhance the diagnostic accuracy through its Q&A system., Conclusions: The RDmaster offers an effective multi-omics differential diagnostic technique and outperforms existing tools and popular large language models, particularly enhancing differential diagnosis in collecting diagnostically beneficial phenotypes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hydrogen sulfide (H 2 S) is a significant actor in the virulence and pathogenicity of fungi. The analysis of endogenous H 2 S in fungi benefits the prevention and treatment of pathogenic infections. Herein, a H 2 S-activated turn-on fluorescent probe named DDX-DNP was developed for the sensitive and selective detection of H 2 S. Using DDX-DNP , the ability of several oral fungi strains to produce H 2 S was identified, which was also validated using a typical chromogenic medium. In addition, DDX-DNP was successfully used for the visual sensing of endogenous H 2 S in fungal cells via microscope, flow cytometry, and colony imaging, along with a specific validation with the co-incubation of H 2 S production inhibitors in living cells. Above all, DDX-DNP could be used for H 2 S detection, the fluorescent imaging of fungi, and even the identification of related fungi.

The present study examined how climate changes may impact the concentrations of lipophilic organochlorines (OCs) in the blood of fasting High Arctic common eiders (Somateria mollissima) during incubation. Polychlorinated biphenyls (PCBs), 1-dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p'-DDE), hexachlorobenzene (HCB) and four chlordane compounds (oxychlordane, trans-chlordane and trans- and cis-nonachlor) were measured in females at chick hatching (n = 223) over 11 years (2007-2017). Firstly, median HCB and p,p'-DDE concentrations increased ~75 % over the study period, whereas median chlordane concentrations doubled (except for oxychlordane). PCB concentrations, in contrast, remained stable over the study period. Secondly, both body mass and clutch size were negatively associated with OC levels, suggesting that females with high lipid metabolism redistributed more OCs from adipose tissue, and that egg production is an important elimination route for OCs. Thirdly, the direct climate effects were assessed using the mean effective temperature (ET: air temperature and wind speed) during incubation, and we hypothesized that a low ET would increase redistribution of OCs. Contrary to expectation, the ET was positively correlated to most OCs, suggesting that a warmer climate may lead to higher OCs levels, and that the impact of ET may not be direct. Finally, potential indirect impacts were examined using the Arctic Oscillation (AO) in the three preceding winters (AO winter 1 - 3 ) as a proxy for potential long-range transport of OCs, and for local spring climate conditions. In addition, we used chlorophyll a (Chla) as a measure of spring primary production. There were negative associations between AO winter 1 and HCB, trans-chlordane and trans-nonachlor, whereas oxychlordane and cis-chlordane were negatively associated with Chla. This suggests that potential indirect climate effects on eiders were manifested through the food chain and not through increased long-range transport, although these relationships were relatively weak., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCB), they have contributed to the exposure of women to persistent organic pollutants (POPs). These compounds can cross the placental barrier and interfere with the hormonal system of newborns., Aim: To determine concentrations of OCPs and PCBs and their xenoestrogenic activity in placentas of women from the PA-MAMI cohort of Panama., Methods: Thirty-nine placenta samples from women in the Azuero peninsula (Panama) were analyzed. Five OCPs [p-p'-dichlorodiphenyldichloroethylene (p-p'-DDE), beta-hexachlorohexane (β-HCH), γ-hexachlorohexane (lindane), hexachlorobenzene (HCB) and mirex] and three PCB congeners (PCB-138, PCB-153 and PCB-180) were quantified in placenta extracts. The xenoestrogenic activity of extracts was assessed with the E-Screen bioassay to estimate the total effective xenoestrogen burden (TEXB)., Results: All placental samples were positive for at least three POP residues and >70% for at least six. The frequencies of quantified OCPs ranged from 100% for p,p'-DDE and HCB to 30.8% for β-HCH. The highest median concentration was for lindane (380.0 pg/g placenta), followed by p,p'-DDE (280.0 pg/g placenta), and HCB (90.0 pg/g placenta). Exposure to p,p'-DDE was associated with greater meat consumption, suggesting that animal fat is a major source of exposure to DDT metabolites. The frequency of detected PCBs ranged between 70 and 90%; the highest median concentration was for PCB 138 (17.0 pg/g placenta), followed by PCB 153 (16.0 pg/g placenta). All placentas were positive in the estrogenicity bioassay with a median TEXB-α of 0.91 pM Eeq/g of placenta. Exposure to lindane was positively associated with the xenoestrogenicity of TEXB- α, whereas this association was negative in the case of exposure to PCB 153., Conclusions: To our best knowledge, this study contributes the first evidence on the presence of POPs and xenoestrogenic burden in placentas from Latin-American women. Given concerns about the consequences of prenatal exposure to these compounds on children's health, preventive measures are highly recommended to eliminate or minimize the risk of OCP exposure during pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Persistent organic pollutants (POPs) are lipophilic compounds that can accumulate in high concentrations in the blubber of marine mammals, which are long-lived, top-level predators in their ecosystems. These compounds, which include DDTs, PCBs, PBDEs, HCHs, and CHLDs, impact mammalian health, including neurological effects, reduced immune system efficiency, and reproductive failure. POPs are transferred from females to their offspring during gestation and lactation, which have implications for the health of newborn marine mammals, particularly first-born offspring who receive higher concentrations. The dynamics of POP transfer during lactation have been studied in a few pinniped species, but there are no comparable studies on living cetaceans. Because life history strategies and behavior of lactating phocids differ from dolphins, a study on delphinid maternal transfer is warranted. To accomplish this, placenta and longitudinally collected blood and milk samples were taken concurrently from trained bottlenose dolphin, Tursiops truncatus, mother/calf pairs to assess the dynamics of maternal contaminant transfer. Initial POP levels in placenta, blood serum, and milk varied by individual and were related to the age and reproductive history of the females. Regardless of initial POP levels, maternal serum and milk concentrations decreased while calf serum POP levels increased over time. Pollutant transfer varied by POP class and by congener. Contaminant transfer efficiency to calves was most apparent for 4- to 6‑chlorine PCBs, DDT isomers p,p'-DDD, p,p'-DDT, o,p'-DDD, and o,p'-DDE, trans-nonachlor, cis-nonachlor, heptachlor epoxide, nonachlor III, and oxychlordane. By the end of the lactation period, calf serum POP levels were considerably greater than those of their mothers, particularly for compounds with fewer chlorines. POP levels were most biomagnified in the calf born to the primiparous female. These results provide critical information on one component of contaminant transfer in the marine ecosystem and for understanding potential risks of POP exposure to developing odontocete calves., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

The Humboldt penguin ( Spheniscus humboldti ) population at the Punta San Juan Marine Protected Area in Peru is considered critical to the long-term sustainability of this endangered species in Peru. Exposure of the rookery to environmental toxicants is a mounting concern because of regional growth of industries and human populations. Whole blood samples were collected from 30 free-ranging penguins in 2011 as part of a broader population health monitoring program. Dried blood spots (DBS) containing 50 µl of blood were prepared and analyzed to assess exposure to five groups of environmental contaminants. Concentrations of elements arsenic, cadmium, iron, lead, mercury, selenium, and thallium were analyzed using inductively coupled plasma mass spectrometry. Persistent organic pollutant concentrations were measured using gas chromatography-tandem mass spectrometry to analyze organochlorine pesticides (OCP; p,p'-DDT, p,p'-DDE, β-hexachlorocyclohexane, t-nonachlor, and oxychlordane), polychlorinated biphenyls (congeners 138 and 153), and polybrominated flame retardants (polybrominated biphenyl-153 and polybrominated diphenyl ether congeners 47 and 99). Per- and polyfluoroalkyl substances, including perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid were measured using liquid chromatography-tandem mass spectrometry. Results revealed low levels of exposure to these selected contaminants, at levels not considered to be of concern for wildlife health. DBS methodology was considered effective in a field-based setting for quantification of whole blood concentrations of environmental contaminants in penguins.

Exposure to environmental pollutants and unhealthy lifestyles are key risk factors for metabolic dysfunction-associated fatty liver disease (MAFLD). While previous studies have suggested links between exposure to organochlorine pesticides (PCBs) and organochlorine pesticides (OCPs) and MAFLD, the results have been inconsistent. Furthermore, the combined effects of PCBs and OCPs on MAFLD and whether lifestyle factors can modify the associations remain unknown. Therefore, this study aimed to investigate the individual and joint effects of PCBs and OCPs on MAFLD and explore the potential modifying role of lifestyle. The study included 1923 participants from Wuhan, China. MAFLD was diagnosed based on ultrasonically diagnosed hepatic steatosis and the presence of overweight/obese, diabetes mellitus, or metabolic dysregulation. Healthy lifestyle score was determined by smoking, alcohol consumption, physical activity, and diet. Logistic regression and weighted quantile sum (WQS) were used to assess associations of individual and mixture of PCBs/OCPs with MAFLD. To explore the potential lifestyle modification, joint associations of PCBs/OCPs and lifestyle on MAFLD were conducted. Single-pollutant analysis showed positive associations of p,p'-DDE, β-HCH, PCB-153, and PCB-180 with MAFLD, with ORs (95% CIs) of 1.18 (1.05, 1.33), 1.57 (1.20, 2.05), 1.45 (1.14, 1.83), and 1.42 (1.12, 1.80), respectively. WQS regression demonstrated a harmful effect of PCBs/OCPs mixture on MAFLD (OR = 1.73, 95% CI = 1.24, 2.43), with β-HCH, p,p'-DDE, and PCB-180 being the major contributors. In the joint association analysis, participants with both high PCBs/OCPs exposure and unhealthy lifestyle have the highest odds of MAFLD. In conclusion, exposure to the mixture of PCBs and OCPs was positively correlated with MAFLD, and adopting a healthy lifestyle can mitigate the adverse impact., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)