05). The relative abundance of Escherichia coli, Peptostreptococcus stomatis, and Bacteroides uniformis showed the most significant association with L3 SMI. There were compositional alterations in intestinal microbiota in patients with liver cirrhosis and muscle wasting. L3 SMI is closely related to E. coli, P. stomatis, and B. uniformis in liver cirrhosis. selleck kinase inhibitor Further interventional studies are needed to confirm whether improving intestinal microbiota can improve the nutritional status of patients with liver cirrhosis.There were compositional alterations in intestinal microbiota in patients with liver cirrhosis and muscle wasting. L3 SMI is closely related to E. coli, P. stomatis, and B. uniformis in liver cirrhosis. Further interventional studies are needed to confirm whether improving intestinal microbiota can improve the nutritional status of patients with liver cirrhosis. Neuronal Ceroid Lipofuscinosis type 2 (CLN2) is a neurodegenerative lysosomal disease which leads to early dementia and death without treatment. The recently available therapy consists of intracerebroventricular enzyme substitution cerliponase alfa. In this report, we describe the evolution of the first French children treated with cerliponase alfa. CLN2 Clinical Rating Scale Motor-Language (CLN2 ML) assesses the motor and language evolution of CLN2 patients. We retrospectively studied patients' medical records clinical symptoms, MRI conclusions, gene mutation, side effects of infusions, patient's age and CLN2 ML scores at diagnosis, at the beginning of enzyme replacement therapy (ERT) and at the last evaluation. Seven patients were included. Average age at diagnosis was 50 months ( ±10) with CLN2 ML score equal to 3.6 [1.5-5]. Average age at the beginning of ERT was 56 months ( ±13) with CLN2 ML score equal to 3.1 [1-5]. At the last available evaluation, average age was 82 months ( ±20) with CLN2 ML score equal to 2.8 [0-5]. Thus, in 26 months, the mean CLN2 ML score only decreased by 0.3 points. However, patients with a CLN2 ML score greater than three at the onset of ERT experienced a stabilisation or improvement of clinical signs, whereas patients with a CLN2 ML score less than three at baseline continue to deteriorate. For patients starting ERT at an early stage of the disease, cerliponase alfa changes the natural history of the disease with a halt in disease progression or even a slight improvement in clinical symptoms.For patients starting ERT at an early stage of the disease, cerliponase alfa changes the natural history of the disease with a halt in disease progression or even a slight improvement in clinical symptoms.The insulin-like growth factor (IGF) system is a critical regulator of growth, especially during fetal development, while also playing a central role in metabolic homeostasis. Endocrine disruptors (EDs) are ubiquitous compounds able to interfere with hormone action and impact human health. For example, exposure to EDs is associated with decreased birthweight and increased incidence of metabolic disorders. Therefore, the IGF system is a potential target for endocrine disruption. This review summarises the state of the science regarding effects of exposure to major classes of endocrine disruptors (dioxins and dioxin-like compounds, polycyclic aromatic hydrocarbons, polybrominated diphenyl ethers, phthalates, perfluoroalkyl substances and bisphenol A) on the IGF system. Evidence from both experimental models (in vitro and in vivo) and epidemiological studies is presented. In addition, possible molecular mechanisms of action and effects on methylation are discussed. There is a large body of evidence supporting the link between dioxins and dioxin-like compounds and IGF disruption, but mixed findings have been reported in human studies. On the other hand, although only a few animal studies have investigated the effects of phthalates on the IGF system, their negative association with IGF levels and methylation status has been more consistently reported in humans. For polybrominated diphenyl ethers, perfluoroalkyl substances and bisphenol A the evidence is still limited. Despite a lack of studies for some ED classes linking ED exposure to changes in IGF levels, and the need for further research to improve reproducibility and determine the degree of risk posed by EDs to the IGF system, this is clearly an area of concern.Cadmium (Cd), an environmental toxicant, is positively associated with fetal growth restriction (FGR). However, the mechanism by which gestational exposure to Cd induces FGR remains unclear. This study designed in vitro and in vivo experiments to explore the role of placental mitophagy in Cd-impaired fetal growth. Based on our case-control study, we also investigated the association of placental mitophagy with reduced progesterone (P4) level and all-cause FGR. We firstly found environmental Cd exposure lowered the P4 content in maternal sera, placentae and amnioticfluids of mice. The level of three mitochondrial P4 synthases, including StAR, CYP11A1 and 3β-HSD, was also reduced in Cd-treated placentae. Furthermore, Cd triggered mitophagy, as determined by the degradation of two mitochondrial proteins HSP60 and COX IV, and the accumulation of co-localizations of TOM20 with LC3B or Parkin in placental trophoblasts. Correspondingly, Cd elevated mitochondrial Parkin level in placental trophoblasts. Mdivi-1, a mitophagy inhibitor, obviously attenuated Cd-induced reduction of placental P4 and FGR in mice. Moreover, mdivi-1 and Parkin siRNA (siR) markedly reversed Cd-caused P4 synthesis inhibition in human placental trophoblasts. Interestedly, the PERK/ATF4 signaling was activated in Cd-stimulated placental trophoblasts. PERK siR inhibited mitochondrial proteins degradation in Cd-stimulated placental trophoblasts. In particularly, mitophagy activation and P4 synthesis suppression occurred in small-for-gestational-age placentae based on our case-control study. Environmental Cd exposure induced FGR via activating PERK-regulated mitophagy and inhibiting P4 synthesis in placentaltrophoblasts. Furthermore, placental mitophagy was related to the reduced progesterone level and all-cause fetal growth restriction based on our case-control study. As above, placental mitophagy maybe the common mechanism of environmental toxicants-impaired fetal growth.