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Abstract This longitudinal study in Mainland China (2021–2022) explored the impact of adverse childhood experiences (ACEs) on complex posttraumatic stress disorder (CPTSD) symptoms, with a focus on the role of self-compassion. Among 18,933 surveyed university students, 21.2% reported experiencing at least one ACE. Results revealed a clear relationship between ACEs and CPTSD symptoms. Furthermore, self-compassion, particularly the dimensions of self-judgment and isolation, moderated the association between retrospective ACEs and posttraumatic stress disorder (PTSD) and disturbance in self-organization (DSO) symptoms. These findings highlight the enduring impact of ACEs on CPTSD symptoms and emphasize the importance of early identification and targeted interventions, especially addressing self-judgment and isolation, to mitigate CPTSD risk among young Chinese adults.

Abstract Background Infant appetitive traits including eating rate, satiety responsiveness, food responsiveness, and enjoyment of food predict weight gain in infancy and early childhood. Although studies show a strong genetic influence on infant appetitive traits, the association of parent and infant appetite is understudied. Furthermore, little research examines the influence of maternal pregnancy dietary intake, weight indicators, and feeding mode on infant appetite. The present study investigated relations of maternal reward-related eating, pregnancy ultra-processed food intake and weight indicators, and feeding mode with infant appetitive traits. Methods Mothers in the Pregnancy Eating Attributes Study (458 mothers enrolled, 367 retained through delivery) completed self-report measures of reward-related eating, and principal component analysis yielded two components: (1) food preoccupation and responsiveness and (2) reinforcing value of food. Mothers completed 24-h dietary recalls across pregnancy, and the standardized NOVA (not an acronym) system categorized recalled foods based on processing level. Maternal anthropometrics were measured across pregnancy. At infant age 6 months, mothers reported on feeding mode and infant appetitive traits. Linear regressions were conducted predicting infant appetitive traits from household income-poverty ratio (step 1); maternal reward-related eating components (step 2); pregnancy ultra-processed food intake (% of energy intake), early pregnancy body mass index, and gestational weight gain (step 3); and exclusive breastfeeding duration (step 4). Results A 1-SD greater maternal food preoccupation and responsiveness was associated with 0.20-SD greater infant satiety responsiveness (p = .005). A 1-SD greater % energy intake from ultra-processed foods during pregnancy was associated with 0.16-SD lower infant satiety responsiveness (p = .031). A 1-SD longer exclusive breastfeeding duration was associated with 0.18-SD less infant food responsiveness (p = .014). Other associations of maternal reward-related eating, pregnancy ultra-processed food intake and weight indicators, and feeding mode with infant appetitive traits were non-significant. Conclusions Proximal early-life environmental factors including maternal pregnancy dietary intake and feeding mode may facilitate or protect against obesogenic infant appetitive traits, whereas infant appetite may not parallel maternal reward-related eating. Further investigation into the etiology of appetitive traits early in development, particularly during solid food introduction, may elucidate additional modifiable risk factors for child obesity. Trial registration Clinicaltrials.gov. Registration ID – NCT02217462 . Date of registration – August 13, 2014.

Abstract Background Excessive intake of ultra-processed foods, formulated from substances extracted from foods or derived from food constituents, may be a modifiable behavioral risk factor for adverse maternal and infant health outcomes. Prior work has predominately examined health correlates of maternal ultra-processed food intake in populations with substantially lower ultra-processed food intake compared to the US population. This longitudinal study investigated relations of ultra-processed food intake with maternal weight change and cardiometabolic health and infant growth in a US cohort. Methods Mothers in the Pregnancy Eating Attributes Study were enrolled at ≤12 weeks gestation and completed multiple 24-Hour Dietary Recalls within six visit windows through one-year postpartum (458 mothers enrolled, 321 retained at one-year postpartum). The NOVA (not an acronym) system categorized food and underlying ingredient codes based on processing level. Maternal anthropometrics were measured throughout pregnancy and postpartum, and infant anthropometrics were measured at birth and ages 2 months, 6 months, and 1 year. Maternal cardiometabolic markers were analyzed from blood samples obtained during the second and third trimesters. Results Holding covariates and total energy intake constant, a 1-SD greater percent energy intake from ultra-processed foods during pregnancy was associated with 31% higher odds of excessive gestational weight gain (p = .045, 95% CI [1.01, 1.70]), 0.68±0.29 mg/L higher c-reactive protein during pregnancy (p = .021, 95% CI [0.10, 1.26]), 6.7±3.4% greater gestational weight gain retained (p = .049, 95% CI [0.03, 13.30]), and 1.09±0.36 kg greater postpartum weight retention (p = .003, 95% CI [0.38, 1.80]). No other significant associations emerged. Conclusions Ultra-processed food intake during pregnancy may be a modifiable behavioral risk factor for adverse maternal weight outcomes and inflammation. Randomized controlled trials are needed to test whether targeting ultra-processed food intake during pregnancy may support optimal maternal health. Trial registration Clinicaltrials.gov. Registration ID – NCT02217462 . Date of registration – August 13, 2014.

Background: Exosomes promote tumor growth and metastasis through intercellular communication, although the mechanism remains elusive. Carboxypeptidase E (CPE) supports the progression of different cancers, including hepatocellular carcinoma (HCC). Here, we investigated whether CPE is the bioactive cargo within exosomes, and whether it contributes to tumorigenesis, using HCC cell lines as a cancer model. Methods: Exosomes were isolated from supernatant media of cancer cells, or human sera. mRNA and protein expression were analyzed using PCR and Western blot. Low-metastatic HCC97L cells were incubated with exosomes derived from high-metastatic HCC97H cells. In other experiments, HCC97H cells were incubated with CPE-shRNA-loaded exosomes. Cell proliferation and invasion were assessed using MTT, colony formation, and matrigel invasion assays. Results: Exosomes released from cancer cells contain CPE mRNA and protein. CPE mRNA levels are enriched in exosomes secreted from high- versus low-metastastic cells, across various cancer types. In a pilot study, significantly higher CPE copy numbers were found in serum exosomes from cancer patients compared to healthy subjects. HCC97L cells, treated with exosomes derived from HCC97H cells, displayed enhanced proliferation and invasion; however, exosomes from HCC97H cells pre-treated with CPE-shRNA failed to promote proliferation. When HEK293T exosomes loaded with CPE-shRNA were incubated with HCC97H cells, the expression of CPE, Cyclin D1, a cell-cycle regulatory protein and c-myc, a proto-oncogene, were suppressed, resulting in the diminished proliferation of HCC97H cells. Conclusions: We identified CPE as an exosomal bioactive molecule driving the growth and invasion of low-metastatic HCC cells. CPE-shRNA loaded exosomes can inhibit malignant tumor cell proliferation via Cyclin D1 and c-MYC suppression. Thus, CPE is a key player in the exosome transmission of tumorigenesis, and the exosome-based delivery of CPE-shRNA offers a potential treatment for tumor progression. Notably, measuring CPE transcript levels in serum exosomes from cancer patients could have potential liquid biopsy applications.

Lactation is associated with a lower risk of subsequent cardiometabolic disease among parous women; however, the underlying mechanisms are unknown. Further, the potential protective effects of lactation on cardiometabolic risk markers at mid-life among high-risk women with past gestational diabetes (GDM) are not established. Using data from the Diabetes & Women’s Health Study (2012–2014; n = 577), a longitudinal cohort of women with past GDM from the Danish National Birth Cohort (1996–2002), we assessed associations of cumulative lactation duration (none, 2 (IQR 24.6, 33.0); 28.6% of participants had T2D, 39.7% had prediabetes, and 41.2% had obesity. Relative risks (95% CI) of T2D for 0–6, 6–12, 12–24, and ≥24 months of cumulative lactation duration compared to none were 0.94 (0.62,1.44), 0.88 (0.59,1.32), 0.73 (0.46,1.17), and 0.71 (0.40,1.27), respectively. Cumulative lactation duration was not significantly associated with any other clinical outcome or continuous biomarker. In this high-risk cohort of middle-aged women with past GDM, T2D, prediabetes, and obesity were common at follow-up, but not associated with history of cumulative lactation duration 9–16 years after the index pregnancy. Further studies in diverse populations among women at mid-age are needed to understand associations of breastfeeding with T2D.

The ceroid lipofuscinosis neuronal 1 (CLN1) disease, formerly called infantile neuronal ceroid lipofuscinosis, is a fatal hereditary neurodegenerative lysosomal storage disorder. This disease is caused by loss-of-function mutations in the CLN1 gene, encoding palmitoyl-protein thioesterase-1 (PPT1). PPT1 catalyzes depalmitoylation of S-palmitoylated proteins for degradation and clearance by lysosomal hydrolases. Numerous proteins, especially in the brain, require dynamic S-palmitoylation (palmitoylation-depalmitoylation cycles) for endosomal trafficking to their destination. While 23 palmitoylacyl transferases in the mammalian genome catalyze S-palmitoylation, depalmitoylation is catalyzed by thioesterases such as PPT1. Despite these discoveries, the pathogenic mechanism of CLN1 disease has remained elusive. Here, we report that in the brain of Cln1-/- mice, which mimic CLN1 disease, the mechanistic target of rapamycin complex-1 (mTORC1) kinase is hyperactivated. The activation of mTORC1 by nutrients requires its anchorage to lysosomal limiting membrane by Rag GTPases and Ragulator complex. These proteins form the lysosomal nutrient sensing scaffold to which mTORC1 must attach to activate. We found that in Cln1-/- mice, two constituent proteins of the Ragulator complex (vacuolar (H+)- ATPase and Lamtor1) require dynamic S-palmitoylation for endosomal trafficking to the lysosomal limiting membrane. Intriguingly, Ppt1 deficiency in Cln1-/- mice misrouted these proteins to the plasma membrane disrupting the lysosomal nutrient sensing scaffold. Despite this defect, mTORC1 was hyperactivated via the IGF1/PI3K/Akt-signaling pathway, which suppressed autophagy contributing to neuropathology. Importantly, pharmacological inhibition of PI3K/Akt suppressed mTORC1 activation, restored autophagy, and ameliorated neurodegeneration in Cln1-/- mice. Our findings reveal a previously unrecognized role of Cln1/Ppt1 in regulating mTORC1 activation and suggest that IGF1/PI3K/Akt may be a targetable pathway for CLN1 disease. [ABSTRACT FROM AUTHOR]