Environmental pollutants have been linked to neurotoxicity and are proposed to contribute to neurodegenerative disorders. The zebrafish model provides a high-throughput platform for large-scale chemical screening and toxicity assessment and is widely accepted as an important animal model for the investigation of neurodegenerative disorders. Although recent studies explore the roles of environmental pollutants in neurodegenerative disorders in zebrafish models, current knowledge of the mechanisms of environmentally induced neurodegenerative disorders is relatively complex and overlapping. This review primarily discusses utilizing embryonic zebrafish as the model to investigate environmental pollutants-related neurodegenerative disease. We also review current applicable approaches and important biomarkers to unravel the underlying mechanism of environmentally related neurodegenerative disorders. We found embryonic zebrafish to be a powerful tool that provides a platform for evaluating neurotoxicity triggered by environmentally relevant concentrations of neurotoxic compounds. Additionally, using variable approaches to assess neurotoxicity in the embryonic zebrafish allows researchers to have insights into the complex interaction between environmental pollutants and neurodegenerative disorders and, ultimately, an understanding of the underlying mechanisms related to environmental toxicants.

UNASSIGNED: The incidence of early-onset colorectal cancer (EOCRC) is increasing globally. This study aims to describe the temporal trends of incidence and explore related risk exposures in early-life at the country level based on the GBD 2019.
UNASSIGNED: Data on the incidence and attributable risk factors of EOCRC were obtained from the GBD 2019. Temporal trends of age-standardized incidence were evaluated by average annual percentage change (AAPC). Early-life exposures were indicated as summary exposure values (SEV) of selected factors, SDI and GDP per capita in previous decades and at ages 0-4, 5-9, 10-14 and 15-19 years. Weighted linear or non-linear regressions were applied to evaluate the ecological aggregate associations of the exposures with incidences of EOCRC.
UNASSIGNED: The global age-standardized incidence of EOCRC increased from 3.05 (3.03, 3.07) to 3.85 (3.83, 3.86) per 100,000 during 1990 and 2019. The incidence was higher in countries with high socioeconomic levels, and increased drastically in countries in East Asia and Caribbean, particularly Jamaica, Saudi Arabia and Vietnam. The GDP per capita, SDI, and SEVs of iron deficiency, alcohol use, high body-mass index, and child growth failure in earlier years were more closely related with the incidences of EOCRC in 2019. Exposures at ages 0-4, 5-9, 10-14 and 15-19 years were also associated with the incidences, particularly for the exposures at ages 15-19 years.
UNASSIGNED: The global incidence of EOCRC increased during past three decades. The large variations at regional and national level may be related with the distribution of risk exposures in early life.

The World Health Organization (WHO) recommends exclusive breastfeeding for the first 6 months of life followed by complementary foods and sustained breastfeeding for at least 2 years, underscoring its pivotal role in reducing infant mortality and preventing various illnesses. This perspective delves into the intricate relationship between breastfeeding practices, early life antibiotic exposure, and infant gut microbiome development, highlighting their profound influence on child health outcomes. Antibiotics are extensively prescribed during pregnancy and childhood, disrupting the microbiome, and are related to increased risks of allergies, obesity, and neurodevelopmental disorders. Breastfeeding is a significant determinant of a healthier gut microbiome, characterized by higher levels of beneficial bacteria such as Bifidobacterium and lower levels of potential pathogens. Despite widespread recognition of the benefits of breastfeeding, gaps persist in healthcare practices and support mechanisms, exacerbating challenges faced by breastfeeding families. This highlights the pressing need for comprehensive research encompassing breastfeeding behaviors, human milk intake, and their impact on infant health outcomes. Additionally, promoting awareness among healthcare providers and families regarding the detrimental effects of unnecessary formula supplementation could facilitate informed decision-making and bolster exclusive breastfeeding rates. Moreover, donor human milk (DHM) is a promising alternative to formula, potentially mitigating disruptions to the infant gut microbiome after antibiotic exposure. Overall, prioritizing breastfeeding support interventions and bridging research gaps are essential steps towards improving child health outcomes on a global scale.

Antibiotics are extensively utilized in the livestock and poultry industry and can accumulate in animals and the environment, leading to potential health risks for humans via food and water consumption. Research on antibiotic toxicity, particularly their impact as endocrine disruptors on the male reproductive system, is still in its nascent stages. This review highlights the toxic effect of antibiotics on the male reproductive system, detailing the common routes of exposure and the detrimental impact and mechanisms of various antibiotic classes. Additionally, it discusses the protective role of food-derived active substances against the reproductive toxicity induced by antibiotics. This review aims to raise awareness about the reproductive toxicity of antibiotics in males and to outline the challenges that must be addressed in future research.

UNASSIGNED: There is mounting evidence indicating that the aging process initiates during early life stages, with in utero the individual\'s environment playing a significant role. Consequently, it is crucial to comprehend the enduring effects of early life circumstances on health in old age.
UNASSIGNED: In this study, we conducted a meta-analysis to examine the effects of the Chinese Famine (1959-1961) on the health of older adults. We also explored potential mechanisms underlying these effects.
UNASSIGNED: The complex interplay between early life circumstances, multiple health-related sectors, and healthy aging necessitates a comprehensive life-course approach and strategic interventions to enhance public health in an aging society.

BACKGROUND: Research demonstrates that chronic exposure to fine particulates (PM2.5) increases risks of neurodevelopmental conditions, such as intellectual disability (ID). Few studies have examined neurodevelopmental health impacts of pollution spikes exceeding 24-h (24-h) PM2.5 guidelines, despite relevance to the regulatory landscape. The current potential for regulatory changes to 24-h PM2.5 standards in the United States makes research on exceedances relevant.
OBJECTIVE: To examine associations between 24-h PM2.5 exceedances and the risk of ID.
METHODS: We conducted a retrospective case-control study of a sample of children in Utah, USA. We used generalized estimating equations to predict odds of ID based on the number of 24-h PM2.5 exceedance days during the preconception period and three trimesters of pregnancy. Exceedance days are defined as per current World Health Organization (WHO) [≥15 μg/m3] and current US Environmental Protection Agency (EPA) [≥35 μg/m3] 24-h guidelines.
RESULTS: PM2.5 exceedances are associated with ID risk during the preconception and first trimester periods and not the second and third trimesters. During the preconception period, each day exceeding 15 μg/m3 or 35 μg/m3 was associated with a 1.023 (CI: 1.011-1.040) or 1.042 (CI: 1.026-1.059, p < 0.001) increase in odds of ID, respectively. During the first trimester, each day exceeding 15 μg/m3 or 35 μg/m3 was associated with a 1.032 (CI: 1.017-1.047) or 1.059 (CI: 1.030-1.088) increase in odds of ID, respectively.
UNASSIGNED: Potential regulatory movement on the US 24-h PM2.5 standard makes research that explicitly studies exceedances highly relevant. Yet few studies examine health effects of exceeding 24-h guidelines for any air pollutants. This study fills important gaps in the literature by examining associations between odds of intellectual disability and the count of days exceeding current 24-h PM2.5 guidelines, as established by the World Health Organization and US Environmental Protection Agency, during the prenatal period. We find that exceedances of both sets of guidelines, during the preconception and first trimester periods, are associated with ID risk.

Mycotoxins are toxic chemicals that adversely affect human health. Here, we assessed the influence of mycotoxin exposure on the longitudinal development of early life intestinal microbiota of Nigerian neonates and infants (NIs). Human biomonitoring assays based on liquid chromatography tandem mass spectrometry were applied to quantify mycotoxins in breast milk (n = 68) consumed by the NIs, their stool (n = 82), and urine samples (n = 15), which were collected longitudinally from month 1-18 postdelivery. Microbial community composition was characterized by 16S rRNA gene amplicon sequencing of stool samples and was correlated to mycotoxin exposure patterns. Fumonisin B1 (FB1), FB2, and alternariol monomethyl ether (AME) were frequently quantified in stool samples between months 6 and 18. Aflatoxin M1 (AFM1), AME, and citrinin were quantified in breast milk samples at low concentrations. AFM1, FB1, and ochratoxin A were quantified in urine samples at relatively high concentrations. Klebsiella and Escherichia/Shigella were dominant in very early life stool samples (month 1), whereas Bifidobacterium was dominant between months 3 and 6. The total mycotoxin levels in stool were significantly associated with NIs\' gut microbiome composition (PERMANOVA, p < 0.05). However, no significant correlation was observed between specific microbiota and the detection of certain mycotoxins. Albeit a small cohort, this study demonstrates that mycotoxins may influence early life gut microbiome composition.

UNASSIGNED: The aim of this study was to compare the differences in incident population, comorbidities, and glucose-lowering drug prescriptions between newly diagnosed patients with early-onset type 2 diabetes mellitus (T2DM) and those with late-onset T2DM to provide real-world evidence for clinical practice.
UNASSIGNED: This study was based on the Shanghai Hospital Link Database (SHLD). Anonymized electronic medical record (EHR) data from 2013 to 2021 were included in this study. Newly diagnosed patients with T2DM were defined as those without related diagnostic records or glucose-lowering medicine prescriptions in the past 3 years. Early-onset T2DM was defined as patients who were aged 18-40 years old at the first visit for T2DM to represent those who were born after the 1980s. And late-onset T2DM was defined as those aged 65-80 years old to represent those who were born in a relatively undeveloped period. Descriptive statistical analyses were performed to describe their incidence number, glucose-lowering drug prescriptions, and comorbidities at the first visit to the hospital between two T2DM groups.
UNASSIGNED: There were a total of 35,457 newly diagnosed patients with early-onset T2DM and 149,108 newly diagnosed patients with late-onset T2DM included in this study. Patients with late-onset T2DM constituted the majority and their number increased by 2.5% on average by years, while the number of patients with early-onset T2DM remained stable each year. Compared with late-onset T2DM patients, more early-onset T2DM patients had dyslipidemia at the first visit to hospitals (9.5% vs 7.7%, P < 0.01) despite their significant age differences. Patients with early-onset T2DM were more likely to use metformin (74.8% vs 46.5, P < 0.01), dipeptidyl peptidase-4 inhibitors (DDP-4i) (16.7% vs 11.2%, P < 0.01), thiazolidinediones (TZD) (14.9% vs 8.4%, P < 0.01), sodium glucose cotransporter 2 inhibitors (SGLT2-i) (0.8% vs 0.3%, P < 0.01), and glucagon-like peptide 1 receptor agonists (GLP-1 RA) (3.7% vs 0.5%, P < 0.01) at their first visit to the hospital.
UNASSIGNED: Different characteristics were observed between patients with early-onset T2DM and those with late-onset T2DM. Compared with patients with late-onset T2DM, those with early-onset T2DM were more prone to dyslipidemia and had novel organ-protective drugs prescribed.

Early-life respiratory syncytial virus (RSV) infection (eRSV) is one of the leading causes of serious pulmonary disease in children. eRSV is associated with higher risk of developing asthma and compromised lung function later in life. Cadmium (Cd) is a toxic metal, widely present in the environment and in food. We recently showed that eRSV re-programs metabolism and potentiates Cd toxicity in the lung, and our transcriptome-metabolome-wide study showed strong associations between S-palmitoyl transferase expression and Cd-stimulated lung inflammation and fibrosis signaling. Limited information is available on the mechanism by which eRSV re-programs metabolism and potentiates Cd toxicity in the lung. In the current study, we used a mouse model to examine the role of protein S-palmitoylation (Pr-S-Pal) in low dose Cd-elevated lung metabolic disruption and inflammation following eRSV. Mice exposed to eRSV were later treated with Cd (3.3 mg CdCl2/L) in drinking water for 6 weeks (RSV+Cd). The role of Pr-S-Pal was studied using a palmitoyl transferase inhibitor, 2-bromopalmitate (BP, 10 µM). Inflammatory marker analysis showed that cytokines, chemokines and inflammatory cells were highest in the RSV+Cd group, and BP decreased inflammatory markers. Lung metabolomics analysis showed that pathways including phenylalanine, tyrosine and tryptophan, phosphatidylinositol and sphingolipid were altered across treatments. BP antagonized metabolic disruption of sphingolipid and glycosaminoglycan metabolism by RSV+Cd, consistent with BP effect on inflammatory markers. This study shows that Cd exposure following eRSV has a significant impact on subsequent inflammatory response and lung metabolism, which is mediated by Pr-S-Pal, and warrants future research for a therapeutic target.

Per-/polyfluoroalkyl substances (PFASs) are persistent organic pollutants and suspected endocrine disruptors.
The aim of this work was to conduct a systematic review with meta-analysis to summarise the associations between prenatal or childhood exposure to PFASs and childhood overweight/obesity.
The search was performed on the bibliographic databases PubMed and Embase with text strings containing terms related to prenatal, breastfeeding, childhood, overweight, obesity, and PFASs. Only papers describing a biomonitoring study in pregnant women or in children up to 18 years that assessed body mass index (BMI), waist circumference (WC), or fat mass in children were included. When the estimates of the association between a PFAS and an outcome were reported from at least 3 studies, a meta-analysis was conducted; moreover, to correctly compare the studies, we developed a method to convert the different effect estimates and made them comparable each other. Meta-analyses were performed also stratifying by sex and age, and sensitivity analyses were also performed.
In total, 484 and 779 articles were retrieved from PubMed and Embase, respectively, resulting in a total of 826 articles after merging duplicates. The papers included in this systematic review were 49: 26 evaluating prenatal exposure to PFASs, 17 childhood exposure, and 6 both. Considering a qualitative evaluation, results were conflicting, with positive, negative, and null associations. 30 papers were included in meta-analyses (19 prenatal, 7 children, and 4 both). Positive associations were evidenced between prenatal PFNA and BMI, between PFOA and BMI in children who were more than 3 years, and between prenatal PFNA and WC. Negative associations were found between prenatal PFOS and BMI in children who were 3 or less years, and between PFHxS and risk of overweight. Relatively more consistent negative associations were evidenced between childhood exposure to three PFASs (PFOA, PFOS, and PFNA) and BMI, in particular PFOS in boys. However, heterogeneity among studies was high.
Even though heterogeneous across studies, the pooled evidence suggests possible associations, mostly positive, between prenatal exposure to some PFASs and childhood BMI/WC; and relatively stronger evidence for negative associations between childhood exposure to PFASs and childhood BMI.