New in JNeurosci: fMRI study from Kim et al. reveals that babies with congenital heart disease have altered sensorimotor and limbic brain networks that cardiovascular surgery improves.
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Congenital heart disease (CHD) affects approximately 1% of live births in the United States and is the most prevalent congenital disorder. Despite advances in neonatal cardiovascular surgery improving survival, neurodevelopmental impairments remain prevalent, impacting motor skills, social behavior, and executive function. Motor deficits and long-term challenges in emotional regulation and memory are particularly common. Recent research using resting-state functional MRI (rs-fMRI) has revealed disorganized brain networks in newborns with CHD. However, those few prior rs-fMRI studies examining the impact of CHD have relied on predefined brain parcellations to compare group-level connectivity, limiting the ability to capture spatial alterations in neonatal brain networks in CHD. Understanding these network-level changes is critical for elucidating mechanisms of neurodevelopmental impairment and identifying early biomarkers of risk. To address these gaps, our study introduces two conceptual advances: 1) a data-driven approach to investigate atypical brain network development in high-risk CHD and 2) the use of a population-sized, independent dataset of healthy newborns to derive a normative set of neonatal brain networks. By analyzing a large rs-fMRI of human newborns (N=448; 219 females and 229 males), we identify atypical brain activity in the sensorimotor and limbic networks of newborns with complex CHD. Notably, before cardiovascular surgery, these networks are split into left and right hemispheric subnetworks. Postoperatively, these components coalesce into a singular, symmetric pattern resembling networks observed in healthy neonates. Our study highlights the potential of rs-fMRI to detect subtle, early functional disruptions in CHD and may inform future biomarkers of neurodevelopmental risk.
Significant Statement Congenital heart disease, the most common congenital disorder, affects 1% of live births and is associated with persistent neurodevelopmental impairments despite improved surgical survival. These deficits, including motor, socio-emotional, and cognitive challenges, may stem from early brain network disruptions. Prior resting-state fMRI studies in CHD relied on predefined parcellations, limiting detection of subtle spatial alterations. In this study, we used a data-driven approach and leveraged an independent normative dataset to define resting-state networks. Comparing CHD patients and healthy controls against these independently derived networks, we reveal atypical sensorimotor and limbic network organization preoperatively, which normalizes post-surgery. These findings highlight the potential of rs-fMRI to identify early biomarkers of neurodevelopmental risk and guide targeted interventions in this high-risk population.
New from Wei-Yao Chin, Shi-Chuen Miaw et al. (國立臺灣大學 National Taiwan University): macrophage Ak4 is vital for defense against bacteria. Ak4 fuels mtDNA synthesis ➡️ boosts mtROS production ➡️ kills pathogens. Loss of Ak4 leads to severe susceptibility.
Chin et al. discovered that macrophage-specific Ak4 regulates mtDNA synthesis, through which it controls mitochondrial biogenesis and mtROS levels and, sub.
Sarcopenic obesity (SO) is characterized by the co-existence of excess adiposity and low muscle performance, with a high prevalence and poor prognosis in the geriatric population.
This systematic review and network meta-analysis (NMA) aims to assess the most effective non-pharmacological interventions for SO patients, including nutrition, exercise, and physical agent therapy.
A systematic search of six electronic databases was conducted from their inception until July 5, 2025, for randomized controlled trials. The NMA utilized a random-effects model, pooled mean difference (MD) and standardized mean difference (SMD), with 95% credible intervals (CrI), accounting for correlations within multi-arm trials. Subgroup analyses and sensitivity analyses were also performed.
Background Neurofascin 155 autoimmune nodopathy (NF155 AN) is a recently recognised immune-mediated neuropathy distinct from chronic inflammatory demyelinating polyneuropathy. While adult-onset cases have been increasingly reported, the juvenile-onset form remains poorly characterised.
Methods We retrospectively analysed 36 patients with NF155 AN, focusing on detailed characterisation of 16 juvenile-onset cases. Their clinical and laboratory data were reviewed.
Results Juvenile-onset patients presented with sensorimotor neuropathy characterised by distal predominant weakness, tremor and sensory ataxia. Motor symptoms were the presenting feature in 75% of patients, which significantly differed from the adult cases (p=0.0015). Postural tremor was more frequent in juvenile patients (94%), while cranial nerve involvement was less common (19%).
Gou Young Koh & team establish ERG and Fli1 as core transcriptional regulators of lymphatic identity, integrity, and function, using human cells and mouse models:
The figure shows stasis of mesenteric lymphatic drainage for a tracer (red) in Prox1-GFP-mice lacking Erg/Fli1 specifically in lymphatic endothelial cells compared with Prox1-GFP-WT mice; with Prox1-GFP marking lymphatic structures (green).
1Center for Vascular Research, Institute for Basic Science, Daejeon, South Korea.
2Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
Address correspondence to: Hyuek Jong Lee or Gou Young Koh, Center for Vascular Research, Institute for Basic Science, Daejeon 34,141, South Korea. Email: hyuekjong.lee@gmail.com (HJL); gykoh@kaist.ac.kr (GYK).
Reprogramming in melanocortin modulates diet-induced obesity.
Hypothalamic proopiomelanocortin (POMC) neurons promote satiety, while agouti-related peptide (AgRP) neurons drive hunger and maintain energy balance.
However, it is not clear how the system is diversified developmentally.
The researchers in this study show that transcription factor Otp act as a developmental ‘‘switch’’ in the hypothalamus and determines whether immature neurons become appetite suppressing (POMC) or appetite stimulating (AgRP).
Disrupting this switch reshapes feeding behavior and protects mice from obesity, revealing how early life programming shapes lifelong metabolic health. sciencenewshighlights ScienceMission https://sciencemission.com/melanocortin-neurons-modulates-diet-induced-obesity
Xu et al. show that a developmental “switch” in the hypothalamus determines whether immature neurons become appetite suppressing or appetite stimulating. Disrupting this switch reshapes feeding behavior and protects mice from obesity, revealing how early-life programming shapes lifelong metabolic health.
Liver regeneration in chronic disease is incompletely understood. In this issue, Jia and coworkers identify a distinct population of hepatocytes expressing Setd4 as key contributors to liver regeneration after chronic injury. Using lineage-tracing and ablation strategies in mouse models of chronic liver damage due to thioacetamide or 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet, the authors show that Setd4+ cells are a long-lasting, dormant, injury-resistant hepatocyte population that survives chronic insults and get activated to support de novo regeneration. Quiescent Setd4+ cells show suppressed metabolic activity maintained by a chromatin state that promotes cellular dormancy and survival (H4K20me3-enriched heterochromatin). After chronic injury, chromatin accessibility remodelling occurs, leading to activation of the cells and initiating regeneration. Selective ablation of Setd4+ cells markedly impaired regenerative recovery, leading to increased fibrosis, higher transaminases, and shorter survival. Interestingly, Setd4+ cells appeared to be essential to initiate de novo regeneration under chronic but not acute conditions. Given the presented data, this newly identified dormant Setd4+ hepatocyte population might hold therapeutic potential to restore regeneration in chronic liver disease.
Full text here: https://www.journal-of-hepatology.eu/article/S0168-8278(…4/fulltext.
EASL — the home of hepatology.
Chronic liver injury and its progression to disease often extend beyond exposure to toxic metabolites or xenobiotics. Recovery from chronic injury, when achieved, depends on de novo regeneration, the underlying mechanisms of which remain poorly understood. Herein, we investigate a specific cell population proposed to be fundamental for de novo regeneration and recovery following chronic injury, aiming to elucidate its regulatory mechanisms.
The kick-off signal for puberty begins in the brain. Specifically, in the hypothalamus, where specific neurons release a hormone that activates the hypophysis, at the base of the skull, which then releases other hormones to start gonad—ovaries or testicles—maturation. This mechanism leading to a fertile organism is the hypothalamic-pituitary-gonadal (HPG) axis.
A study by Spain’s National Cancer Research Center (CNIO) has discovered in animal models that two previously unsuspected elements are also involved in this hormone regulating system: microglia—defensive cells of the nervous system—and the protein RANK, which contributes to bone remodeling and is essential in the functioning of the mammary glands.
The work is published in the journal Science. It is led by Eva González-Suárez, head of the CNIO Transformation and Metastasis Group, who discovered in 2010 the key role played by RANK in the development of breast cancer. The first author is Alejandro Collado, a researcher from the same group and co-corresponding author.