CD2AP deficiency aggravates Alzheimer's disease phenotypes and pathology through p38 MAPK activation.

Background: Alzheimer's disease (AD) is the most common form of neurodegenerative disorder, which is characterized by a decline in cognitive abilities. Genome-wide association and clinicopathological studies have demonstrated that the CD2-associated protein (CD2AP) gene is one of the most important genetic risk factors for AD. However, the precise mechanisms by which CD2AP is linked to AD pathogenesis remain unclear.

The efficacy and safety of dual-target rTMS over dorsolateral prefrontal cortex (DLPFC) and cerebellum in the treatment of negative symptoms in first-episode schizophrenia: Protocol for a multicenter, randomized, double-blind, sham-controlled study.

Background And Objective: The dorsolateral prefrontal cortex (DLPFC) - cerebellum circuit has been implicated in the pathogenesis of negative symptoms of schizophrenia (SZ). Both areas are considered separate targets for repetitive transcranial magnetic stimulation (rTMS) treatment, showing potential for improving negative symptoms. However, there is still a lack of research that targets both DLPFC and cerebellum simultaneously.

Perspectives on Enhanced Measurement-Based Care Among Healthcare Providers, Adults, Adolescent Patients with Major Depressive Disorder and Pediatric Family Members: A Multicenter Online Investigation.

Objective: Measurement-based care (MBC) is an emerging, objective, and systematic evidence-based practice for monitoring symptom severity and treatment efficacy to assist clinicians in developing individualized treatment strategies for patients with major depressive disorder (MDD). This study aimed to identify the barriers and facilitators of enhanced MBC (eMBC) in the outpatient setting to clarify the eMBC utilization dilemma.

Methods: Between September 2022 and June 2023, we collected the opinions of healthcare providers, adult and adolescent patients, and family members of adolescent patients via online surveys.

Protocol for generating a pericyte reporter zebrafish line Ki(pdgfrb-P2A-GAL4-VP16) using a CRISPR-Cas9-mediated knockin technique.

Pericytes, the mural cells that envelop small blood vessels, play crucial roles in the formation of the blood-brain barrier (BBB). Here, we present a protocol for generating a pericyte reporter zebrafish line Ki(pdgfrb-P2A-GAL4-VP16) using a CRISPR-Cas9-mediated knockin technique. We describe steps for identifying efficient single guide RNA (sgRNA), constructing donor plasmid, and generating and maintaining the knockin line.

Self-amplifying mRNA vaccines protect elderly BALB/c mice against a lethal respiratory syncytial virus infection.

Respiratory Syncytial Virus (RSV) represents a significant threat, being a primary cause of critical lower respiratory tract infections and fatalities among infants and the elderly worldwide, and poses a challenge to global public health. This urgent public health challenge necessitates the swift development of safe and effective vaccines capable of eliciting robust immune responses at low doses. Addressing this need, our study investigated five self-amplifying RNA (sa-mRNA) candidate vaccines that encode the various pre-fusion conformations of the RSV fusion protein.

An RNA editing strategy rescues gene duplication in a mouse model of MECP2 duplication syndrome and nonhuman primates.

Duplication of methyl-CpG-binding protein 2 (MECP2) gene causes MECP2 duplication syndrome (MDS). To normalize the duplicated MECP2 in MDS, we developed a high-fidelity Cas13Y (hfCas13Y) system capable of targeting the MECP2 (hfCas13Y-gMECP2) messenger RNA for degradation and reducing protein levels in the brain of humanized MECP2 transgenic mice. Moreover, the intracerebroventricular adeno-associated virus (AAV) delivery of hfCas13Y-gMECP2 in newborn or adult MDS mice restored dysregulated gene expression and improved behavior deficits.

Thinning of central foveal thickness in the retina of patients with schizophrenia.

The neural retina shares a common embryonic origin with the brain and yields pathological changes like that in the brain in various neuropsychiatric disorders, including schizophrenia. Non-invasive examination by optical coherence tomography (OCT) revealed retinal structure abnormalities in patients with schizophrenia. This study investigated retina structures in 29 patients with schizophrenia and 25 healthy controls in a Chinese Han ethnic population with spectral domain OCT.

Hypo-osmolarity promotes naive pluripotency by reshaping cytoskeleton and increasing chromatin accessibility.

Introduction: Cell fate determination and transition are of paramount importance in biology and medicine. Naive pluripotency could be achieved by reprogramming differentiated cells. However, the mechanism is less clear.

Super-resolution imaging of fast morphological dynamics of neurons in behaving animals.

Neurons are best studied in their native states in which their functional and morphological dynamics support animals' natural behaviors. Super-resolution microscopy can potentially reveal these dynamics in higher details but has been challenging in behaving animals due to severe motion artifacts. Here we report multiplexed, line-scanning, structured illumination microscopy, which can tolerate motion of up to 50 μm s while achieving 150-nm and 100-nm lateral resolutions in its linear and nonlinear forms, respectively.

A small-molecule screen identifies novel aging modulators by targeting 5-HT/DA signaling pathway.

The risk of many human diseases including cardiovascular diseases, cancer, neurodegenerative diseases, and musculoskeletal disorders rises significantly in the elderly. With the increase in the aging population, it is becoming increasingly important to understand the biology of healthy aging and develop interventions that slow down the aging process or prevent age-related diseases. In this study, by a high-throughput screen in Caenorhabditis elegans (C.

Adenine base editors induce off-target structure variations in mouse embryos and primary human T cells.

Background: The safety of CRISPR-based gene editing methods is of the utmost priority in clinical applications. Previous studies have reported that Cas9 cleavage induced frequent aneuploidy in primary human T cells, but whether cleavage-mediated editing of base editors would generate off-target structure variations remains unknown. Here, we investigate the potential off-target structural variations associated with CRISPR/Cas9, ABE, and CBE editing in mouse embryos and primary human T cells by whole-genome sequencing and single-cell RNA-seq analyses.

Peripheral molecular and brain structural profile implicated stress activation and hyperoxidation in methamphetamine use disorder.

Aim: Methamphetamine use disorders (MUDs) cause widespread disruptions in metabolomic and immunologic processes, highlighting the need for new therapeutic approaches. The purpose of this study was to find molecular and neuroimaging biomarkers for methamphetamine addiction.

Methods: In this study, we recruited 231 patients with MUD at varying stages of withdrawal and 40 healthy controls to quantify the blood levels of 52 molecules using enzyme-linked immunosorbent assay.

Glutamatergic Circuits in the Pedunculopontine Nucleus Modulate Multiple Motor Functions.

The functional role of glutamatergic (vGluT2) neurons in the pedunculopontine nucleus (PPN) in modulating motor activity remains controversial. Here, we demonstrated that the activity of vGluT2 neurons in the rostral PPN is correlated with locomotion and ipsilateral head-turning. Beyond these motor functions, we found that these rostral PPN-vGluT2 neurons remarkably respond to salient stimuli.

Age-related differences of the time-varying features in the brain functional connectivity and cognitive aging.

Brain functional modular organization changes with age. Considering the brain as a dynamic system, recent studies have suggested that time-varying connectivity provides more information on brain functions. However, the spontaneous reconfiguration of modular brain structures over time during aging remains poorly understood.

Evolutionary neural architecture search for automated MDD diagnosis using multimodal MRI imaging.

Major depressive disorder (MDD) is a prevalent mental disorder with serious impacts on life and health. Neuroimaging offers valuable diagnostic insights. However, traditional computer-aided diagnosis methods are limited by reliance on researchers' experience.

Mediator MED23 controls oligodendrogenesis and myelination by modulating Sp1/P300-directed gene programs.

Gaining the molecular understanding for myelination development and regeneration has been a long-standing goal in neurological research. Mutations in the transcription cofactor Mediator Med23 subunit are often associated with intellectual disability and white matter defects, although the precise functions and mechanisms of Mediator in myelination remain unclear. In this study, we generated a mouse model carrying an Med23 mutation that has been identified in a patient with hypomyelination features.

Improving the growth and intestinal colonization of Escherichia coli Nissle 1917 by strengthening its oligopeptides importation ability.

Escherichia coli Nissle 1917 (EcN), the probiotic featured with well-established safety in different host, is emerging as a favored chassis for the construction of engineered probiotics for disease treatment. However, limited by the low intestinal colonization ability of EcN, repeated administration is required to maximize the health benefits of the EcN-derived engineered probiotics. Here, using fecal metabolites as "metabolites pool", we developed a metabolomic strategy to characterize the comprehensive metabolic profile of EcN.