BACKGROUND: Obesity is characterized by excessive fat accumulation, which is related with abnormal pluripotency of mesenchymal stem cells (MSCs). Recently, there is growing evidence that the disorder of maternal vitamin D (VD) intake is a well-known risk factor for long-term adverse health outcomes to their offspring. Otherwise, less is known of its repercussion and underlying mechanisms on the different differentiation potential of MSCs.
METHODS: Four-week-old female C57BL/6J mice were fed with different VD reproductive diets throughout the whole pregnancy and lactation. The characteristics of BMSCs from their seven-day male offspring, VDR knockdown establishment of HuMSCs and HuMSCs under the different VD interventions in vitro were confirmed by flow cytometry, RT-PCR, and immunofluorescence. The roles of VD on their mitochondrial dysfunction and differentiation potential were also investigated. Then their remaining weaned male pups were induced by administrating high-fat-diet (HFD) for 16 weeks and normal fat diet was simultaneously as controls. Their lipid accumulation and adipocytes hypertrophy were determined by histological staining and related gene expressions.
RESULTS: Herein, it was proved that imbalance of early-life VD intake could significantly aggravate the occurrence of obesity by inducing the adipogenesis through affecting the VD metabolism and related metabolites (P < 0.05). Moreover, abnormally maternal VD intake might be involved on the disorders of differentiation potential to inhibit the maintenance of MSCs stemness through increasing the productions of ROS, which was accompanied by impairing the expression of related genes on the adipo-osteogenic differentiation (P < 0.05). Moreover, it was along with increasing potential of adipogenic differentiation of MSCs as higher ROS in the state of VD deficiency, while excessive maternal VD status could conversely enhance the osteogenic differentiation with slightly lower ROS (P < 0.05). Furthermore, the underlying mechanisms might be involved on the mitochondria dysfunctional, especially the mitophagy, by activating the LC3b, P62 and etc. using in vivo and in vitro studies (P < 0.05).
CONCLUSIONS: These findings demonstrated that imbalance of early-life VD intake could target ROS-mediated crosstalk between mitochondrial dysfunction and differentiation potential of MSCs, which was significantly associated with the later obesity. Obviously, our results could open up an attractive modality for the benefits of suitable VD intake during the pregnancy and lactation.

BACKGROUND: Limited research has explored the impact of mosquito repellents exposure during early life on ADHD symptoms. This study aimed to explore the associations of exposure to mosquito repellents from pregnancy to 3 years old and the prevalence of ADHD-like behaviours among children aged 3-9 years, and further identify the sensitive exposure period.
METHODS: A cross-sectional study was conducted, including 12 275 children in Hefei City, China. Exposure was self-reported via primary caregivers. ADHD-like behaviours were measured by the Swanson, Nolan and Pelham, version IV scale (SNAP-IV), and Conners\' Parent Rating Scale (CPRS). Cross-over analysis, binary logistic regression and linear regression were employed.
RESULTS: After adjusting for confounding variables, early-life exposure to mosquito repellents was associated with a higher risk of ADHD-like behaviours (OR = 1.81, 95% CI = 1.49-2.19). By comparing the strength of the association for each subgroup, we found exposure during 1-3 years old was a sensitive period (OR = 1.89, 95% CI = 1.25-2.87) by the cross-over analysis. Furthermore, we found a dose-response relationship in which the likelihood of ADHD-like behaviours increased with children\'s early-life mosquito repellents exposure dose.
CONCLUSIONS: Early-life exposure to mosquito repellents is linked with an elevated risk of ADHD-like behaviours in children, with a sensitive period identified during 1-3 years old.

BACKGROUND: Stroke is a life-threatening condition that causes a major medical burden globally. The currently used methods for the prevention or prediction of stroke have certain limitations. Exposure to tobacco in early life, including smoking during adolescence and maternal smoking during pregnancy, can affect adolescent development and lead to several negative outcomes. However, the association between early-life tobacco exposure and stroke is not known.
METHODS: In this prospective cohort study, for the analyses involving exposure to maternal smoking during pregnancy and age of smoking initiation, we included 304,984 and 342,893 participants, respectively., respectively from the UK Biobank. Cox proportional hazard regression model and subgroup analyses were performed to investigate the association between early-life tobacco exposure and stroke. Mediation analyses were performed to identify the mediating role of biological aging in the association between early tobacco exposure and stroke.
RESULTS: Compared with participants whose mothers did not smoke during pregnancy, participants whose mothers smoked during pregnancy showed an 11% increased risk of stroke (HR: 1.11, 95% CI: 1.05-1.18, P < 0.001). Compared with participants who never smoked, participants who smoked during adulthood, adolescence and childhood showed a 22%, 24%, and 38% increased risk of stroke during their adulthood, respectively. Mediation analysis indicated that early-life tobacco exposure can cause stroke by increasing biological aging.
CONCLUSIONS: This study reveals that exposure to tobacco during early life is associated with an increased risk of experiencing a stroke, and increased biological aging can be the underlying mechanism.

Early-life exposure to environmental neurotoxicants is known to have lasting effects on organisms. In this study, we aim to investigate the impacts of PQ exposure during early developmental stages and adult re-challenge in aged mice on non-motor neurobehavior. Two mouse models, which were exposed once during early life stage and re-exposure at adulthood, were created to explore the long-term effects of PQ on non-motor neurobehavior. As the results showed, early-life exposure to PQ caused impairment in working memory and cognitive ability in aged male mice, but not in female mice, exhibiting a sex-specific impairment. Moreover, male mice that were re-challenged with PQ at adulthood following early-life exposure also exhibited non-motor neurobehavioral disorders. Notably, re-exposure to PQ exacerbated neurobehavioral disorders and anxiety levels compared to single exposure during different life stages. Collectively, early-life exposure to PQ can result in irreversible impairments in non-motor neurobehavior and increase susceptibility to subsequent insults in male mice, but not in female mice, suggesting greater sensitivity in male rodents to PQ-induced non-motor neurobehavioral deficits.

Epidemiological investigations show that noise exposure in early life is associated with health and cognitive impairment. The gut microbiome established in early life plays a crucial role in modulating developmental processes that subsequently affect brain function and behavior. Here, we examined the impact of early-life exposure to noise on cognitive function in adolescent rats by analyzing the gut microbiome and metabolome to elucidate the underlying mechanisms. Chronic noise exposure during early life led to cognitive deficits, hippocampal injury, and neuroinflammation. Early-life noise exposure showed significant difference on the composition and function of the gut microbiome throughout adolescence, subsequently causing axis-series changes in fecal short-chain fatty acid (SCFA) metabolism and serum metabolome profiles, as well as dysregulation of endothelial tight junction proteins, in both intestine and brain. We also observed sex-dependent effects of microbiota depletion on SCFA-related beneficial bacteria in adolescence. Experiments on microbiota transplantation and SCFA supplementation further confirmed the role of intestinal bacteria and related SCFAs in early-life noise-exposure-induced impairments in cognition, epithelial integrity, and neuroinflammation. Overall, these results highlight the homeostatic imbalance of microbiota-gut-brain axis as an important physiological response toward environmental noise during early life and reveals subtle differences in molecular signaling processes between male and female rats.

Di (2-ethyl-hexyl) phthalate (DEHP), one of endocrine-disrupting chemicals (EDCs), has widespread concern due to its serious health hazards. Exposure to DEHP in the early stage of life affects fetal metabolic and endocrine function, which even would cause genetic lesions. To date, it is widely believed that the increasing incidence of childhood obesity and diabetes in adolescents is related to the impact of DEHP on glucose and lipid homeostasis in children. However, there remains a knowledge gap to recognize these adverse effects. Thus, in this review, besides the exposure routes and levels of DEHP, we further outline the effects of early-life exposure to DEHP on children and potential mechanisms, focusing on the aspect of metabolic and endocrine homeostasis.

The potential health risks associated with simultaneous presence of residues of heavy metals and antibiotics in the environment and food have been of wide concern. However, the adverse health effects of combined heavy metal and antibiotic exposure at low doses remain unclear. In this study, the effects of combined exposure to florfenicol and copper at low doses during early life on toxicity, gut microbiota, drug resistance genes, and the fecal metabolome were investigated in Sprague-Dawley (SD) rats. The results showed that combined exposure induced inflammatory responses and visceral injury as well as faster weight gain compared with florfenicol or copper exposure alone. Alpha and beta diversity indices indicated that the composition of the gut microbiota and the abundance of bacteria related to energy intake and disease in the combined exposure group were significantly altered. The increase in resistance genes (floR, fexA) induced by florfenicol exposure was suppressed under combined exposure to florfenicol and copper. The fecal metabolome also demonstrated that metabolic pathways related to energy intake and liver injury were significantly affected in the combined exposure group. In conclusion, this study shows that combined exposure to florfenicol and copper during early life can pose a nonnegligible health risk even if the exposure concentration of florfenicol or copper is below the safe limit.

BACKGROUND: Galacto-oligosaccharides (GOS) are non-digestible food ingredients that promote the growth of beneficial bacteria in the gut. This study investigated the protective effect of the early-life GOS supplement on the piglets\' gut function against the oxidative stress induced by lipopolysaccharide (LPS)-challenge.
METHODS: Eighteen neonatal piglets were assigned to three groups including CON, LPS and LPS + GOS groups. The piglets in CON group and LPS group received physiological saline, while those in LPS + GOS group received GOS solution for 13 d after birth. On d 14, the piglets in LPS group and LPS + GOS group were injected with LPS solutions, while the piglets in CON group were injected with the same volume of physiological saline.
RESULTS: The results showed that the early-life GOS supplement blocked the LPS-induced reactive oxygen species (ROS) secretion, malondialdehyde (MDA) production and the increase of pro-apoptotic factor expression. Meanwhile, the early-life GOS supplement improved the activities of antioxidant enzymes, disaccharidase enzymes activities, and digestive enzymes activities, and increased the mRNA abundance of the gene related to nutrient digestion and absorption and the relative protein expression of tight junction. The study also showed that the early-life GOS supplement improved the expression of Hemeoxygenase-1 (HO-1) and NAD(P)H/quinone acceptor oxidoreductase-1 (NQO-1), and activated the AMP-activated protein kinase (AMPK).
CONCLUSIONS: These results suggested that GOS enhanced the gut function, reduced the ROS production and pro-apoptotic factors gene expression, and activated the AMPK signaling pathway in LPS-challenged piglets.

The Taicang and Wuqiang cohort study (TAWS) was established to examine the association between early-life nutrition and children\'s health, and to explore the potential roles of maternal health, metabolites and microbiota in children\'s health in two different regions of China.
A total of 7041 mother-child pairs were recruited during early pregnancy (n=4035, 57.3%) or delivery phase (n=3006, 42.7%) from health centres or hospitals in Taicang and Wuqiang. Mother-child pairs were followed up three times during pregnancy, once during delivery, and 7-10 times in the 3 years after delivery. Questionnaires were used to collect data on diet, supplementary intake, physical activity, depression scale, disease occurrence, feeding practice and development quotient of children. Anthropometric measurements of mothers and their children were assessed at each visit. Pregnancy outcomes were extracted from medical records. Biospecimens were collected and stored, including venous blood, cord blood, urine, stool, breast milk, cord and placenta.
Data from the TAWS cohort showed different baseline characteristics of participants at the two sites of TAWS. Abnormal metabolism occurred among newborns whose mothers were diagnosed with gestational diabetes mellitus. Maternal serum folic acid above 14.5 ng/mL at early pregnancy was associated with a reduced risk of delivering small-for-gestational-age newborns.
The association between maternal nutrition and the health of offspring will be examined at various follow-up visits. Biomarkers will be analysed to assess the associations between early-life nutrition and child development, immunity and health. Strategic recommendations for optimal infant feeding practices, obesity prevention and routine healthcare items will be developed and proposed based on the findings from the study. Children in this prospective cohort study will be followed up once a year until age 12 years to further examine the relationships between early-life nutrition and children\'s long-term development and health.

This study examines the effect of CEOs\' early-life traumatic experience on firm-specific stock price crash risk. Drawing on the idea of natural experiments, we take the Great Famine in China as an external traumatic event which cannot be selected or controlled by human. The analysis points out that compensation psychology and irrational defense psychology after the trauma of Great Famine are important factors that cause CEOs to hoard bad news. Based on a large sample of Chinese companies from 2007 to 2017, we find evidence that CEOs who experienced the Great Famine during early-life tend to hoard bad news, which result in higher stock price crash risk. The more severe and prolonged the Great Famine that the CEOs experienced, the greater the effect of this traumatic experience. CEOs decision-making power enhances the adverse effect of CEOs\' early-life traumatic experiences on crash risk. Findings of this study contributes to the literature by providing a new explanation for the stock price crash risk, which is of great significance for the sustained and healthy development of capital markets.