Ferroptosis is a mode of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation. It is closely linked to the pathophysiological processes in many diseases. Since our publication of the first ferroptosis database in 2020 (FerrDb V1), many new findings have been published. To keep up with the rapid progress in ferroptosis research and to provide timely and high-quality data, here we present the successor, FerrDb V2. It contains 1001 ferroptosis regulators and 143 ferroptosis-disease associations manually curated from 3288 articles. Specifically, there are 621 gene regulators, of which 264 are drivers, 238 are suppressors, 9 are markers, and 110 are unclassified genes; and there are 380 substance regulators, with 201 inducers and 179 inhibitors. Compared to FerrDb V1, curated articles increase by >300%, ferroptosis regulators increase by 175%, and ferroptosis-disease associations increase by 50.5%. Circular RNA and pseudogene are novel regulators in FerrDb V2, and the percentage of non-coding RNA increases from 7.3% to 13.6%. External gene-related data were integrated, enabling thought-provoking and gene-oriented analysis in FerrDb V2. In conclusion, FerrDb V2 will help to acquire deeper insights into ferroptosis. FerrDb V2 is freely accessible at http://www.zhounan.org/ferrdb/.

Schizophrenia is a chronic disorder characterized by specific positive and negative primary symptoms, social behavior disturbances and cognitive deficits (e.g., impairment in working memory and cognitive flexibility). Mounting evidence suggests that altered excitability and inhibition at the molecular, cellular, circuit and network level might be the basis for the pathophysiology of neurodevelopmental and neuropsychiatric disorders such as schizophrenia. In the past decades, human and animal studies have identified that glutamate and gamma-aminobutyric acid (GABA) neurotransmissions are critically involved in several cognitive progresses, including learning and memory. The purpose of this review is, by analyzing emerging findings relating to the balance of excitatory and inhibitory, ranging from animal models of schizophrenia to clinical studies in patients with early onset, first-episode or chronic schizophrenia, to discuss how the excitatory-inhibitory imbalance may relate to the pathophysiology of disease phenotypes such as cognitive deficits and negative symptoms, and highlight directions for appropriate therapeutic strategies.

INTRODUCTION: With the advancement of disease‐modifying therapies for Alzheimer's disease (AD), validating plasma biomarkers against cerebrospinal fluid (CSF) and positron emission tomography (PET) standards is crucial in both research and real‐world settings. METHODS: We measured plasma phosphorylated tau (p‐tau)217, p‐tau181, amyloid beta (Aβ)1‐40, Aβ1‐42, and neurofilament light chain in research and real‐world cohorts. Participants were categorized by brain amyloid status using US Food and Drug Administration/European Medicines Agency–approved CSF or PET methods. RESULTS: Plasma p‐tau217 and p‐tau217/Aβ1‐42 demonstrated superior accuracy in detecting brain amyloid pathologies, with area under the curve from 0.94 to 0.97 in all cohorts. Specificity was lower in the real‐world cohort but improved significantly by integrating demographic and clinical factors, aligning performance with research cohorts. Additionally, plasma biomarkers exhibited strong correlations with their CSF counterparts and PET standardized uptake value ratios, with significant associations in amyloid‐positive participants. DISCUSSION: Plasma p‐tau217 and p‐tau217/Aβ1‐42 are effective diagnostic tools. However, patient demographics, apolipoprotein E ε4 status, and cognitive condition must be considered to improve specificity in the clinical practice. Highlights: Plasma phosphorylated tau (p‐tau)217 and p‐tau217/amyloid beta (Aβ)1‐42 demonstrated exceptional accuracy (area under the curve: 0.94–0.97) in detecting brain amyloid pathologies across both research (Southern China Aging Brain Initiative [SCABI]‐1, SCABI‐2) and real‐world clinical practice (RCP) cohorts. Incorporating patient‐specific factors (sex, age, apolipoprotein E ε4, cognitive status) improved diagnostic specificity in the clinical RCP cohort, aligning its performance with that of research cohorts. Plasma biomarkers, particularly p‐tau217 and their ratios, showed robust correlations with cerebrospinal fluid biomarkers and positron emission tomography amyloid standardized uptake value ratios, underscoring their value as non‐invasive diagnostic alternatives. Plasma p‐tau217 and p‐tau217/Aβ1‐42 proved highly effective in diagnosing amyloid burden, offering a practical solution to bridge research advancements with real‐world clinical practice.