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PubMed2026

The association between normalized creatinine-to-cystatin C ratio and incident circadian syndrome in middle-aged and older adults: a national cohort study.

BACKGROUND: Evidence on the association between the normalized creatinine-to-cystatin C ratio (NCCR) and Circadian Syndrome (CircS) in the general population remains scarce. This study aimed to investigate this relationship using data from middle-aged and elderly participants in the China Health and Retirement Longitudinal Study (CHARLS). METHODS: We conducted a cross-sectional analysis of 5,981 participants (2011 wave) and a prospective cohort analysis of 2,053 participants (2015 wave, median follow-up 4.0 years). CircS was defined as a cluster including elevated blood pressure, dyslipidemia, hyperglycemia, abdominal obesity, depression, and abnormal sleep duration. RESULTS: During follow-up, 552 participants developed incident CircS. A significant inverse association was observed: the risk of new-onset CircS progressively decreased with higher baseline NCCR levels. After adjusting for multiple confounders, each standard deviation increase in NCCR was associated with a 40% reduced odds of CircS (adjusted odds ratio = 0.60, 95% confidence interval: 0.48 to 0.75). Subgroup and dose-response analyses confirmed the robustness of this inverse relationship. CONCLUSIONS: In conclusion, a lower NCCR is independently associated with an elevated risk of developing CircS. These findings support NCCR's role as a practical serum indicator of sarcopenia and implicate muscle loss as a potentially key underlying pathway in the pathogenesis of Circadian Syndrome.

Humans↗

PubMed2026

A status update on the unkept promise of high-frequency spinal cord stimulation for treatment-refractory chronic migraine.

INTRODUCTION: Chronic migraine (CM) refractory to conventional pharmacotherapy (r-CM) remains a debilitating neurological condition with limited therapeutic options. High-frequency spinal cord stimulation at 10 kilohertz (HF-SCS) has recently emerged as a distinct neuromodulatory paradigm for this patient population. Unlike traditional spinal cord stimulation, HF-SCS operates above the frequency range that generates paresthesia, thereby eliminating stimulation-induced sensation while potentially engaging unique analgesic mechanisms. AREAS COVERED: This focused narrative review synthesizes the available clinical evidence, technical considerations, and mechanistic hypotheses specifically pertaining to cervical HF-SCS for refractory chronic migraine (r-CM). The authors further provide their expert perspectives on the future of this technology as a treatment option for refractory chronic migraine. EXPERT OPINION: Current data from prospective open-label studies and retrospective case series suggest that cervical HF-SCS may reduce monthly migraine days, facilitate conversion from chronic to episodic migraine patterns in some implanted patients, and may improve headache-related disability and quality of life over at least 52 weeks of follow-up. The paresthesia-free nature of HF-SCS confers a distinct advantage for both patient tolerability and future trial design, as it permits sham-controlled methodologies that have historically been impossible with conventional neurostimulation. However, these findings remain preliminary and should be considered hypothesis-generating pending confirmation in adequately powered randomized sham-controlled trials.

Humans↗

PubMed2026

Continuous Intraperitoneal Insulin Infusion for People With Type 1 Diabetes: A Literature Review and International Position Statement.

Achieving glucose targets without hypoglycaemia is the treatment goal in type 1 diabetes. Structured education, intensified insulin injection regimens, continuous glucose monitoring, automated insulin delivery, and ongoing support from a multidisciplinary team all support people with type 1 diabetes to achieve this goal. Despite these advances, significant barriers to achieving optimal management remain. Continuous intraperitoneal insulin infusion has comparable or better glucose outcomes to continuous subcutaneous insulin infusion and may reduce the frequency of hypoglycaemia, including severe episodes. Intraperitoneal insulin may be considered as a treatment modality for children and adults with type 1 diabetes using optimised intensive insulin therapy for whom subcutaneous insulin has failed due to lipoatrophy, -dystrophy or -hypertrophy, local allergy, subcutaneous insulin resistance or co-existing skin conditions. Failure of subcutaneous insulin may result in recurrent or unexplained severe hypoglycaemia or hyperglycaemia. Intraperitoneal insulin may also be considered as a treatment modality for people with type 1 diabetes with severe needle-phobia, and for those being considered for islet cell or pancreatic transplantation, or where transplantation is not available. This paper summarises current intraperitoneal insulin delivery technology, its potential risks and benefits, and an expert position statement. It is intended for use by diabetes specialist healthcare professionals, and as a reference for other healthcare professionals, commissioners, payors, people with diabetes, their carers, and advocates.

Humans↗

PubMed2026

Influence of nicotine on protein expression around hydrophilic osseointegrated implants: A proteomic study in male rats.

OBJECTIVE: To ensure the success of dental implant treatment, various factors must be considered, including osseointegration and systemic conditions. There is evidence in the literature that smokers may exhibit alterations in tissue healing, which can compromise the success of implant rehabilitation. Therefore, this study aimed to investigate the influence of nicotine on the protein profile of bone tissue around hydrophilic implants during the osseointegration process in rats. DESIGN: Bone tissue samples from the control and nicotine groups (n = 3 per group) were subjected to protein extraction, mass spectrometry, and bioinformatic analyses. Protein identification was performed using Proteome Discoverer 2.1 software and the SEQUEST algorithm, and the protein data were compared with those of a protein database of Rattus norvegicus obtained from UniProt. RESULTS: A total of 740 proteins were detected in both the control group and the nicotine-exposed group. Among them, the proteins biglycan, periostin and histone H4 were highlighted because of their higher abundance in the healthy implant group, while they were reduced in the nicotine-exposed group. CONCLUSIONS: Nicotine has the potential to alter the protein profile of bone tissue around hydrophilic implants during osseointegration, which may impair tissue remodeling and healing.

Animals↗

PubMed2026

Identification of CD55 as a downstream factor of EP4 receptor signaling in colorectal cancer cells.

Prostaglandin E2 (PGE2) signaling through the E-type prostanoid 4 (EP4) receptor has been implicated in the pathophysiology of colorectal cancer (CRC). We herein identified decay-accelerating factor, also known as CD55, as a novel CRC-associated downstream factor of the EP4 receptor. The integration of transcriptomic profiling of PGE2-stimulated HCA-7 human colon cancer cells with analyses of cancer genomic databases predicted CD55 as a potential EP4 receptor-regulated target. Inhibitor-based experiments showed the induction of CD55 after a PGE2 stimulation required the EP4 receptor and Gi protein in HCA-7 cells, whereas protein kinase A signaling was dispensable. In combination with a toxicogenomic database analysis, p38 mitogen-activated protein kinase (MAPK) was identified as the predominant effector connecting the EP4 receptor to CD55 upregulation. A single-cell RNA-seq re-analysis of human CRC tissues revealed CD55 upregulation and p38 MAPK-related gene set enrichment in epithelial cells expressing the EP4 receptor, suggesting that this induction mechanism may operate in a subset of epithelial cells in clinical specimens. Collectively, these results delineate a PGE2/EP4 receptor/Gi protein/p38 MAPK signaling axis that induces CD55 expression in HCA-7 cells and epithelial tumor cells, provide new mechanistic clues for understanding the regulation of complement regulatory molecule CD55 expression by prostaglandin signaling.

Humans↗

PubMed2026

Genetic Diversity Analysis of Red Fox Populations (Vulpes vulpes L., 1758) in Natural and Anthropogenic Isolation.

This study presents a comparative analysis of the genetic structure and diversity of three red fox (Vulpes vulpes L.) populations representing different microevolutionary scenarios: panmixia (free-ranging Belarusian foxes), geographic isolation (free-ranging Scottish foxes), and anthropogenic selection (farm-bred foxes). Using a validated set of STR markers, multivariate statistical analysis was conducted to assess the genetic structure and the degree of genetic erosion across the studied groups. The wild red fox population in Belarus has been shown to maintain a state close to panmixia (PHWE = 0.090), characterized by a high effective population size (Ne = 694) and high allelic diversity. The island population from Scotland exhibits moderate gene pool depletion (Ne = 75.9) and a pronounced heterozygote deficiency (FIS = 0.18). Critical genetic erosion, which was characterized by a minimal effective population size (Ne = 60.2) and allelic fixation, was detected in the farm-bred group. The genetic distance between farm-bred and wild foxes (FST = 0.279; p = 0.001) reflects both the phylogeographic divergence between the Nearctic ancestors of farmed lineages and Palearctic wild populations, and the consequences of prolonged anthropogenic isolation, genetic drift, and selective breeding. These data indicate that artificial isolation and the impacts of genetic drift and targeted selection lead to a substantial depletion of the species' adaptive potential.

Animals↗

PubMed2026

Artificial Intelligence Technologies in Nursing Clinical Decision-Making: An Umbrella Review.

AIM: To describe contemporary peer-reviewed literature on artificial intelligence in nurses' clinical decision-making. METHODS: An umbrella review of literature reviews. DATA SOURCES: Four major databases were searched for reviews published between 2019 and 2024. RESULTS: Sixteen literature reviews reported on 965 nursing artificial intelligence primary studies. The studies focused on technology development and emerging performance evaluations, whilst real-world testing or implementation in nursing clinical settings was rare. Rigorous comparative analyses were lacking. While artificial intelligence demonstrates promise in decision-making, challenges such as a lack of controlled studies, algorithmic bias, limited reproducibility and insufficient clinical trials hinder its practical impact. Ethical concerns, transparency and patient data privacy issues pose barriers to AI integration in nursing practice. Ethical and legal guidelines for patient privacy are needed and should be taught along with AI literacy training for nurses. CONCLUSIONS: Artificial intelligence has the potential to enhance clinical nursing decision-making, although evidence is limited by too few examples of nurse participation during development. Underutilisation in administrative nursing functions hinders implementation. Nurses should assume a central role in the design and development of AI applications to ensure that these technologies address the realities of nursing practice. With such improvements, artificial intelligence can transform nursing practice, improve nurses' clinical decision-making and ultimately enhance consumer healthcare outcomes. PATIENT OR PUBLIC INVOLVEMENT: No Patient or Public Involvement. REPORTING METHOD: While there is no reporting checklist for umbrella reviews, the PRISMA guide for systematic reviews was followed.

Artificial Intelligence↗

PubMed2026

The combination of morphogenic regulators BABY BOOM and GRF-GIF improves maize transformation efficiency and promotes leaf regeneration.

Transformation is an indispensable tool for plant genetics and functional genomics. Although stable transformation in maize is no longer a major obstacle, there remains a need for accessible and efficient methods for academic laboratories. Here, we present the GGB system, a rapid and efficient approach optimized for immature embryo transformation in B104 and other maize lines. This system combines two distinct morphogenetic regulators, the wheat GRF4-GIF1 chimera and the maize BABY BOOM (BBM) transcription factor (hence the name "GGB") with a modified QuickCorn protocol, enabling regeneration of transformed maize plantlets in c. 2 months with an efficiency 7-fold higher than when compared to either morphogenic factor used in isolation. Expression of both regulators did not significantly affect development, eliminating the need to excise them after regeneration. However, transmission of the transgenic GGB construct through pollen was significantly reduced, potentially aiding transgenic line containment. We show that the GGB system is adaptable for CRISPR-Cas9 editing and reporter line generation. Furthermore, stable GGB transformants exhibited high leaf regeneration capacity via somatic embryogenesis. RNA-seq time-course profiling of GGB leaf cultures identified additional factors that could promote regeneration and led to the discovery of asparagine and trehalose as additional media components that significantly enhanced leaf regeneration.

Zea mays↗

PubMed2026

Implementation of Mobile Health Intervention Targeting Belongingness and Burdensomeness: An Ecological Momentary Assessment Study of Self-Injurious Thoughts and Behaviors in LGBTQ+ Individuals.

OBJECTIVE: The goal of this paper was to test a mobile health intervention designed to reduce self-injurious thoughts and behaviors in LGBTQ+ individuals. The intervention consisted of brief messages aimed at increasing feelings of belongingness and meaning. METHOD: We recruited LGBTQ+ individuals (N = 55) with past-month self-injurious thoughts and/or behaviors. Participants completed 14 days of ecological momentary assessment (EMA) of minority stress, thwarted belongingness, perceived burdensomeness, and self-injurious thoughts and behaviors. Then, participants were randomly assigned to receive brief messages designed to instill belongingness and meaning/purpose, or no intervention for 14 days. Then, participants completed an additional 14 days of EMA. RESULTS: Our results showed that participants in the control condition had significant increases in self-injurious thoughts and planning over time, whereas those in the intervention condition showed no significant change. For self-injurious behavior, thwarted belongingness, and perceived burdensomeness, there were significant decreases in the intervention condition, but no changes in the control condition. CONCLUSIONS: These results provide support for the interpersonal theory of suicide and indicate a potentially scalable mobile health intervention. PUBLIC HEALTH SIGNIFICANCE: This paper found evidence that a brief mobile health intervention reduced suicidal and non-suicidal self-injurious thoughts and behaviors among LGBTQ+ individuals.

Humans↗

PubMed2026

Characterization of ZIC5 expression in esophageal squamous cell carcinoma and its association with patient survival.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy known for its aggressive nature and poor prognosis. The present study aimed to investigate the expression levels and clinical importance of the Zic family member 5 (ZIC5) gene in ESCC. Gene expression data and survival information obtained from The Cancer Genome Atlas and Gene Expression Omnibus were utilized. In 176 patients with surgically resected ESCC, immunohistochemical analysis was conducted to validate the expression of ZIC5 protein in cancerous and adjacent tissues. The findings of the present study revealed a significant upregulation of ZIC5 in ESCC compared with normal tissues (P<0.05), which was further corroborated by immunohistochemistry exhibiting a notable association between ZIC5 expression and clinical parameters such as tumor size, invasion depth, lymph node metastasis and TNM staging (P<0.05). Survival analysis further indicated that high ZIC5 expression was an independent prognostic factor for poor outcomes in patients with ESCC (hazard ratio=1.519; 95% CI: 1.017-2.269; P<0.05). In addition, bioinformatic analyses predicted that hsa-microRNA-212-5p may regulate ZIC5 mRNA and gene enrichment analysis suggested that ZIC5 may facilitate ESCC progression through involvement in the cell cycle and DNA repair pathways. In conclusion, ZIC5 is highly expressed in ESCC and associated with a poor prognosis, indicating its potential as a therapeutic target and biomarker for ESCC management. Further studies are warranted to elucidate the precise mechanisms underlying the role of ZIC5 in ESCC progression.

ESCC↗

PubMed2026

Metagenome-scale modeling to assess microbiome metabolic complementarity for precision microbiota transplantation therapies.

Fecal microbiota transplantation (FMT) holds therapeutic promise beyond recurrent Clostridioides difficile infection, but clinical outcomes remain unpredictable and donor-selection strategies remain limited, in part because the role of donor‒recipient metabolic interactions in shaping the post-FMT community remains poorly understood. Here, we leverage metagenome-scale metabolic modeling to quantify metabolic niche complementarity between donor and recipient microbiomes and predict post-FMT community composition. Using MICOM-derived metabolic models, we show that donor genomes whose metabolic flux profiles are more dissimilar from the recipient community colonize at significantly higher rates in a murine FMT model. In a human IBS trial, the same metric predicted post-FMT community composition via leave-one-out cross-validation and captured known disease-associated alterations in short-chain fatty acid, sulfur, and gas metabolism. We then performed 2,548 in silico FMT simulations between IBS-D/M patients and donors from the OpenBiome biobank to evaluate personalized donor screening, identifying super-donors characterized by high taxonomic diversity, broad metabolic niche coverage, and community interaction networks dominated by cross-feeding rather than competition. Together, these results support metabolic niche complementarity as a potential determinant of post-FMT community composition and provide a mechanistic basis for evaluating donor-recipient metabolic compatibility. This framework offers a scalable approach for generating testable hypotheses for personalized donor selection.

Fecal Microbiota Transplantation↗

PubMed2026

Sutimlimab for cold agglutinin disease: an updated perspective from approval to real-world clinical treatment.

INTRODUCTION: Sutimlimab, a classical complement pathway (CP) inhibitor, was approved in 2022 in the US, EU, and Japan for the treatment of cold agglutinin disease (CAD), a rare form of autoimmune hemolytic anemia (AIHA) characterized by CP‑mediated extravascular hemolysis and circulatory symptoms related to IgM‑mediated red blood cell (RBC) agglutination. This review reexamines the clinical trial data and compares those findings with published real‑world experience (RWE), providing clinicians with efficacy and safety data that extend beyond the clinical trial experience in this rare AIHA. AREAS COVERED: The first-in-human trials, the two seminal clinical trials (CARDINAL and CADENZA), and the published post‑marketing RWE are presented. Literature searches for CAD and sutimlimab were conducted in PubMed and in abstracts from ASH and EHA from 2016 to present. All articles and abstracts regarding sutimlimab and CAD were included. EXPERT OPINION: Long-term data from clinical trials and published RWE support the safety and efficacy of sutimlimab. Targeting the CP as primary therapy for CAD offers a unique, targeted management strategy that minimizes exposure to immunosuppressive regimens. The rapid onset of sutimlimab's activity provides a potentially lifesaving treatment option in situations where immediate control of hemolysis is critical. Opportunities remain to increase our understanding of the role of complement inhibition combined with immunosuppressive therapy in CAD. The impact of complement inhibition on morbidity and mortality in CAD remains to be determined.

Humans↗

PubMed2026

Pangenome-wide identification and expression analysis of the chalcone synthase (CHS) gene family in five yellowhorn spp.

Chalcone synthase (CHS) is a pivotal enzyme in flavonoid biosynthesis involved in plant development, defense, and secondary metabolism. Xanthoceras sorbifolium (yellowhorn) is a medicinal and ornamental species with high resistance to environmental stresses, but its CHS gene family remains uncharacterized. We performed a pangenome-wide identification of CHS genes across five yellowhorn genomes (Xzs4, Xwf8, Xjg, Xg11, and Xzg2). Across the five yellowhorn genomes, 27 CHS genes were identified and classified into four core pangenes, present in all five genomes, and two dispensable genes, present only in a subset of genomes. Phylogenetic analysis grouped these genes into three major clades, and chromosomal mapping and duplication analyses identified four tandemly duplicated gene pairs under purifying selection. The analyses of conserved structural features, including protein motifs and exon-intron organization, together with promoter cis-regulatory elements and gene ontology annotation, further indicated the potential involvement of CHS genes in flavonoid biosynthesis and stress-responsive mechanisms. Gene expression profiling identified significant upregulation of Xg11_CHS1 and Xg11_CHS3 under cold and drought stress, with tissue-specific expression patterns. These findings provide valuable insights into the evolution, functional diversification, and stress-responsive roles of the CHS gene family, identifying candidate genes for future studies targeting stress tolerance and flavonoid biosynthesis in yellowhorn.

Acyltransferases↗

PubMed2025

The molecular mechanism of cuproptosis and research progress in pancreatic diseases.

PURPOSE: Cuproptosis has been proven to be a novel mode of cell death, distinct from other types of cell death such as necrosis, ferroptosis, pyroptosis, and apoptosis. This study aims to systematically review the molecular mechanisms of cuproptosis in recent years and its research progress in pancreatic diseases. METHODS: By searching PubMed and Web of Science databases, 113 key literatures were included for thematic analysis, covering the molecular mechanism of cuproptosis and its role in the occurrence and development of pancreatic cancer, acute and chronic pancreatitis, diabetes, pancreatic cyst, pancreatic injury and pancreatic neuroendocrine tumor. RESULTS: Cuproptosis refers to the accumulation of copper ions in cells, which leads to instability of ferritin and aggregation of acylated proteins, resulting in oxidative stress-related cell death. Recent studies have shown that cuproptosis plays an important role in the occurrence and development of various pancreatic diseases, such as pancreatic cancer, acute and chronic pancreatitis, diabetes, pancreatic cysts, pancreatic injuries and pancreatic neuroendocrine tumor. The inducers of cuproptosis, such as disulfiram, chloroquinolones, and perilla phenols, alleviate pancreatic cancer by promoting cell cuproptosis. Copper chelators such as tetraethylenepentamine and tetrathiomolybdate promote the recovery of pancreatic injury by inhibiting cell cuproptosis. CONCLUSIONS: Cuproptosis plays a crucial role in the pathogenesis of pancreatic diseases. Further research on the cuproptosis pathway may become a potential target for the treatment of pancreatic diseases.

Animals↗

PubMed2026

Transcriptomic analysis provides molecular insights into the innate immune defense of Mactra veneriformis against Vibrio alginolyticus infection.

Mactra veneriformis is an economically important bivalve mollusc in China, but its aquaculture is frequently threatened by Vibrio infections, particularly Vibrio alginolyticus. To investigate the molecular immune response of M. veneriformis to V. alginolyticus, we performed RNA-seq analysis of hepatopancreatic tissues collected at 48 h post-infection, the peak mortality time point, with PBS-injected individuals used as controls. Infection with V. alginolyticus caused severe histopathological damage in the hepatopancreas and resulted in a cumulative mortality of 53.3% over 14 d, compared with 3.3% in the control group. Transcriptomic analysis identified 2623 differentially expressed genes (DEGs), including 1585 significantly up-regulated genes and 1038 down-regulated genes. KEGG enrichment analysis demonstrated that DEGs were significantly enriched in immune related and metabolism pathways, including the JAK-STAT signaling pathway, RIG-I-like receptor (RLR) signaling pathway, and cytochrome P450 (CYP450) signaling pathway. Collectively, these findings revealed candidate immune related genes (tlr3, tlr5, myd88, nfkb1, il-17d, and ifi44l), a putative TLR-MyD88-NF-κB signaling axis, and KEGG signaling pathways, including JAK-STAT, RLR and CYP450, that may be involved in the innate immune response of M. veneriformis to V. alginolyticus infection. These results provide a transcriptomic basis for understanding host-pathogen interactions in this species and highlight candidate genes and pathways for future functional validation and potential application in disease-resistance breeding.

Animals↗

PubMed2026

Analysis of the Relationship between Early Clinical Factors and Glasgow Outcome Scale in Patients With Traumatic Brain Injury.

OBJECTIVE: This study aimed to evaluate the association between early clinical factors and the Glasgow outcome scale (GOS) in patients with traumatic brain injury (TBI). METHODS: We conducted a retrospective analysis of 98 TBI patients who underwent emergency surgery between January 2021 and January 2024. Based on GOS scores at 6 months post-surgery, patients were classified into a favorable outcome group (GOS ≥ 4, defined as moderate disability or good recovery, n = 58) and an unfavorable outcome group (GOS < 4, i.e., death, persistent vegetative state, or severe disability, n = 40). Baseline and early clinical parameters were compared between groups. Statistically significant variables from univariate analysis were entered into a multivariate logistic regression model to identify independent prognostic factors. RESULTS: Significant intergroup differences were observed in age, time from injury to surgery, bleeding site, midline shift, Glasgow coma scale (GCS) score at admission, blood glucose level, and D-dimer level (all p < 0.05). Multivariate analysis confirmed that age, time from injury to surgery, GCS score, blood glucose, and D-dimer level were independent predictors of GOS (all p < 0.05). CONCLUSION: Early clinical factors, including age, time to surgery, GCS score, blood glucose, and D-dimer level, independently influence GOS in TBI patients. Time from injury to surgery emerged as a potentially modifiable factor in this cohort, suggesting that minimizing delays may improve outcomes.

Humans↗

PubMed2026

Venomous Lepidoptera: defensive toxin systems, venom composition, and clinical significance.

Venomous Lepidoptera constitute an underrecognized yet medically significant group of toxin-producing arthropods that employ contact-mediated defensive envenomation through specialized integumentary structures such as setae, spines, and scoli. Unlike actively stinging arthropods, these insects deliver venom passively upon contact, eliciting a diverse spectrum of clinical manifestations collectively termed lepidopterism. Clinical outcomes range from localized pain and dermatitis to severe systemic effects, including hemorrhagic syndromes, complement activation, and chronic inflammatory disorders. Recent advances in proteomic and transcriptomic technologies have transformed our understanding of lepidopteran venoms, revealing unexpectedly complex toxin repertoires comprising serine proteases, phospholipases, pore-forming proteins, disulfide-rich peptides, neuroactive RF-amide peptides, and immune-modulating components. These findings have provided new insights into the molecular basis of toxicity, host-pathogen interactions, and the evolutionary diversification of venom systems within Lepidoptera. This review synthesizes current knowledge on the morphology of venom-delivery structures, venom composition, mechanisms of action, and associated clinical manifestations, while highlighting medically important taxa, particularly species of the genus Lonomia. The successful development of antivenom against Lonomia envenomation underscores the translational relevance of lepidopteran toxin research and its potential for therapeutic innovation. By integrating molecular, clinical, and evolutionary perspectives, this review repositions venomous Lepidoptera as a legitimate and important component of arthropod toxinology. Furthermore, it identifies critical methodological limitations and key knowledge gaps, providing a framework for future investigations aimed at advancing our understanding of toxin biology, immunopathology, and the development of novel biomedical applications.

Animals↗

PubMed2026

Hippocampal teneurin-4 knockdown promotes depression-like behavioral phenotypes by disrupting oligodendrocyte differentiation in mice.

Depression is one of the most prevalent mental disorders worldwide. The limited clinical efficacy of current antidepressants highlights identifying new therapeutic targets. Emerging evidence suggests that dysfunction of oligodendrocyte lineage cells contributes to the pathophysiology of depression. Teneurin-4 (Tenm4), a transmembrane protein that promotes oligodendrocyte differentiation and myelination, has been implicated in psychiatric disorders in genome-wide association studies; however, its causal role remains unclear. To determine whether Tenm4 contributes to depressive-like behavioral phenotypes, we examined Tenm4 protein expression in mice exposed to repeated forced swimming stress and generated hippocampal Tenm4 knockdown (Tenm4KD) mice. Chronic stress reduced Tenm4 expression levels in the hippocampus. Mice with hippocampus-specific Tenm4KD exhibited depressive-like behaviors, accompanied by reduced hippocampal myelin basic protein. Importantly, administration of clemastine, a myelin formation promoter, inhibited the reduction of myelin and attenuated depression-like behavioral phenotypes. Immunohistochemical analysis showed that Tenm4KD significantly decreased the number of mature oligodendrocyte cells and increased in the number of oligodendrocyte precursor cells, without changes in the total number of oligodendrocyte lineage cells. This study provides the first evidence that hippocampal Tenm4 deficiency induces depression-like behavior phenotypes through impaired oligodendrocyte differentiation and promoting demyelination. Our results identify Tenm4 as a molecular regulator of stress-induced behavioral phenotypes and suggest that it might represent a potential therapeutic target for mood disorders associated with demyelination.

Animals↗