Projectome-based characterization of hypothalamic peptidergic neurons in male mice.

The hypothalamus coordinately regulates physiological homeostasis and innate behaviors, yet the detailed arrangement of hypothalamic axons remains unclear. Here we mapped the whole-brain projections of over 7,000 hypothalamic neurons expressing distinct neuropeptides in male mice, identifying 2 main classes and 31 types using single-neuron projectome analysis. These classes/types exhibited regionally biased soma distribution and specific neuropeptide enrichment.

Single-cell spatial transcriptomic atlas of the whole mouse brain.

A comprehensive atlas of genes, cell types, and their spatial distribution across a whole mammalian brain is fundamental for understanding the function of the brain. Here, using single-nucleus RNA sequencing (snRNA-seq) and Stereo-seq techniques, we generated a mouse brain atlas with spatial information for 308 cell clusters at single-cell resolution, involving over 4 million cells, as well as for 29,655 genes. We have identified cell clusters exhibiting preference for cortical subregions and explored their associations with brain-related diseases.

TMEM63B functions as a mammalian hyperosmolar sensor for thirst.

Thirst drives animals to reinstate water homeostasis by fluid intake. An increase in blood osmolality is thought to induce thirst by activating a hyperosmolar sensor expressed in the subfornical organ (SFO), but the molecular identity of this sensor remains elusive. Here, we provide behavioral and functional evidence to show that TMEM63B functions as a mammalian hyperosmolar sensor for thirst in SFO neurons.

A comprehensive study of AAV tropism across C57BL/6 mice, BALB/c mice, and crab-eating macaques.

Recombinant adeno-associated viruses (AAVs) have been widely used for gene delivery and gene therapy. However, certain AAV serotypes exhibited distinct transduction patterns among different mouse strains or between mice and non-human primates (NHPs). These variations prompted us to investigate the AAV tropism of 21 capsid variants using barcoded AAV libraries among different tissues in C57BL/6 and BALB/c mice, as well as in crab-eating macaques.

Oscillatory control over representational geometry of sequence working memory in macaque frontal cortex.

To process sequential streams of information, e.g., language, the brain must encode multiple items in sequence working memory (SWM) according to their ordinal relationship.

S-ketamine exposure in early postnatal period induces social deficit mediated by excessive microglial synaptic pruning.

The impact of general anesthetics on neurodevelopment is highly controversial in terms of clinical and preclinical studies. Evidence mounted in recent years indicated development of social cognitions was more susceptible to general anesthesia in early life. However, the behavioral characterization during adolescence and underlying mechanisms remains unclear.

Genetically encoded tension heterogeneity sculpts cardiac trabeculation.

The myocardial wall arises from a single layer of cardiomyocytes, some delaminate to create trabeculae while others remain in the compact layer. However, the mechanisms governing cardiomyocyte fate decisions remain unclear. Using single-cell RNA sequencing, genetically encoded biosensors, and in toto live imaging, we observe intrinsic variations in expression and its association with trabecular fate.

Metabolic engineering of Lactobacilli spp. for disease treatment.

Background: A variety of probiotics have been utilized as chassis strains and engineered to develop the synthetic probiotics for disease treatment. Among these probiotics, Lactobacilli, which are generally viewed as safe and capable of colonizing the gastrointestinal tract effectively, are widely used. We review recent advancements in the engineering of Lactobacilli for disease treatment.

Dynamic alterations in bacterial and fungal microbiome and inflammatory cytokines following SRV-8 infection in cynomolgus monkeys.

While viral infections can disturb the host gut microbiome, the dynamic alterations in microbial composition following infection remain poorly characterized. This study identified SRV-8-infected monkeys and classified them into five groups based on infection progression. 16S rRNA amplicon sequencing revealed significant alterations in the relative and inferred absolute abundance of bacterial genera , , , and during the early stage of SRV-8 infection, coinciding with provirus formation.

An antidepressant mechanism underlying the allosteric inhibition of GluN2D-incorporated NMDA receptors at GABAergic interneurons.

-methyl-d-aspartate receptors (NMDARs), key excitatory ion channels, have gained attention as anti-depression targets. NMDARs consist of two GluN1 and two GluN2 subunits (2A-2D), which determine their pharmacological properties. Few compounds selectively targeting GluN2 subunits with antidepressant effects have been identified.

A Novel Mouse Model Unveils Protein Deficiency in Truncated CDKL5 Mutations.

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5 mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits.

Comparative molecular landscapes of immature neurons in the mammalian dentate gyrus across species reveal special features in humans.

Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity, learning and memory, but their evolutionary changes across species and specialized features in humans remain poorly understood. Here we performed machine learning-augmented analysis of published single-cell RNA-sequencing datasets and identified macaque imGCs with transcriptome-wide immature neuronal characteristics. Our cross-species comparisons among humans, monkeys, pigs, and mice showed few shared (such as DPYSL5), but mostly species-specific gene expression in imGCs that converged onto common biological processes regulating neuronal development.

Structural insights into the diverse actions of magnesium on NMDA receptors.

Magnesium (Mg) is a key regulatory ion of N-methyl-ᴅ-aspartate (NMDA) receptors, including conferring them to function as coincidence detectors for excitatory synaptic transmission. However, the structural basis underlying the Mg action on NMDA receptors remains unclear. Here, we report the cryo-EM structures of GluN1-N2B receptors and identify three distinct Mg-binding pockets.

Distinct effects of early-stage and late-stage socioeconomic factors on brain and behavioral traits.

Socioeconomic status (SES) is a time-varying multidimensional construct with ill-defined dimension-specific and age-specific effects on brain and behavior. We investigated these effects in 4,228 young adults. From 16 socioeconomic indicators, assessed for early (0-10 years) and late (>10 years) stages, we constructed family, provincial, family adverse and neighborhood adverse socioeconomic dimensions.

Harnessing omics data for drug discovery and development in ovarian aging.

Background: Ovarian aging occurs earlier than the aging of many other organs and has a lasting impact on women's overall health and well-being. However, effective interventions to slow ovarian aging remain limited, primarily due to an incomplete understanding of the underlying molecular mechanisms and drug targets. Recent advances in omics data resources, combined with innovative computational tools, are offering deeper insight into the molecular complexities of ovarian aging, paving the way for new opportunities in drug discovery and development.

Aberrant functional gradient of thalamo-cortical circuitry in major depressive disorder and generalized anxiety disorder.

Background: Functional gradient analysis provides insights into the brain's macroscale organization; however, the differences in thalamo-cortical gradients between major depressive disorder (MDD) and generalized anxiety disorder (GAD) remain unclear. Investigating these heterogeneities may uncover disorder-specific neural mechanisms and enhance diagnostic precision, addressing the distinct yet overlapping features of these affective disorders.

Methods: Resting-state functional MRI data were acquired from 88 healthy controls, 53 patients with MDD, and 28 patients with GAD.

Murine gut microbial interactions exert antihyperglycemic effects.

The correlations between gut microbiota and host metabolism have been studied extensively, whereas little relevant work has been done to investigate the impact of gut microbial interactions on host metabolism. With the use of a bacteriocin-targeting strategy, we aimed to identify the gut microbes associated with glucose and lipid metabolism by adjusting the gut microbial composition of mice fed a high-fat diet. To fulfill this goal, a Listeria monocytogenes (Lmo)-derived bacteriocin Lmo2776 secretion module was constructed and integrated into the genome of Escherichia coli Nissle 1917 (EcN), yielding the Lmo2776-secreting strain EcN-2776.

The interaction between central and peripheral immune systems in methamphetamine use disorder: current status and future directions.

Methamphetamine (METH) use disorder (MUD) is characterized by compulsive drug-seeking behavior and substantial neurotoxicity, posing a considerable burden on individuals and society. Traditionally perceived as a localized central nervous system disorder, recent preclinical and clinical studies have elucidated that MUD is a multifaceted disorder influenced by various biological systems, particularly the immune system. Emerging evidence suggests that both central and peripheral immune responses play a crucial role in the initiation and persistence of MUD.

Single-Cell Transcriptomes of Immune Cells from Multiple Compartments Redefine the Ontology of Myeloid Subtypes Post-Stroke.

The activation and infiltration of immune cells are hallmarks of ischemic stroke. However, the precise origins and the molecular alterations of these infiltrating cells post-stroke remain poorly characterized. Here, a murine model of stroke (permanent middle cerebral artery occlusion [p-MCAO]) is utilized to profile single-cell transcriptomes of immune cells in the brain and their potential origins, including the calvarial bone marrow (CBM), femur bone marrow (FBM), and peripheral blood mononuclear cells (PBMCs).

Alterations in temporal-spatial brain entropy in treatment-resistant depression treated with nitrous oxide: Evidence from resting-state EEG.

Objective: Entropy analysis can quantify the dynamic states of the brain and reflect its information processing capacity. Nitrous oxide has shown rapid antidepressant effects in treatment-resistant depression (TRD) patients, but its biomarkers are not yet established.

Methods: We recruited 44 TRD patients and randomly assigned them to two groups: one received a 1-hour nitrous oxide inhalation treatment, while the other received a placebo.

Machine learning-based algorithm of drug-resistant prediction in newly diagnosed patients with temporal lobe epilepsy.

Objectives: To develop a predicted algorithm for drug-resistant epilepsy (DRE) in newly diagnosed temporal lobe epilepsy (TLE) patients.

Methods: A total of 139 newly diagnosed TLE patients were prospectively enrolled, and long-term video EEG monitoring was recorded. Clinical evaluations, including seizure frequency and antiseizure medications (ASMs) usage, were collected and prospectively followed up for 24 months.

Transformer-based fusion model for mild depression recognition with EEG and pupil area signals.

Early detection and treatment are crucial for the prevention and treatment of depression; compared with major depression, current researches pay less attention to mild depression. Meanwhile, analysis of multimodal biosignals such as EEG, eye movement data, and magnetic resonance imaging provides reliable technical means for the quantitative analysis of depression. However, how to effectively capture relevant and complementary information between multimodal data so as to achieve efficient and accurate depression recognition remains a challenge.

Effects of housing conditions on health and gut microbiome of female cynomolgus monkeys and improvement of welfare by checking menstruation under socially housed condition.

Laboratory non-human primates (NHPs) are commonly subjected to social deprivation in various scientific researches. However, the impact of social deprivation on gut microbiome remains largely unknown. We examined the health status and gut microbiota of female cynomolgus monkeys housed in isolation or social conditions and found that social deprivation brought adverse effects to monkeys by inhibiting their growth, remodeling the immune status, and decreasing the level of beneficial biochemical parameters.

Dynamic changes of excitatory and inhibitory synapses in layer II/III of the primary motor cortex after peripheral nerve repair.

Peripheral nerve injury disrupts communication between the primary motor cortex (M1) and the target muscle, leading to alterations in synaptic plasticity within the lesion projection zone (LPZ). While nerve repair holds the potential to restore this pathway and further modulate synaptic plasticity within the LPZ, the underlying mechanisms remain incompletely understood. In this study, 42 adult male Sprague Dawley rats underwent immediate repair following unilateral median nerve transection and categorized the functional recovery of the affected limb into three phases: the injury phase, recovery phase, and rehabilitation phase, corresponding to stages of muscle non-reinnervation, gradual reinnervation, and completed reinnervation, respectively.