The mandible is essential for facial structure and oral function. Jaw bone marrow mesenchymal stromal cells (JBMMSCs) exhibit self-renewal and multi-lineage potential for bone regeneration, but are compromised by post-injury inflammation, poor vascularization, and osteogenic microenvironment disruption. This study evaluated the effect of ultrashort wave (USW) therapy on enhancing JBMMSCs function and promoting mandibular repair. In a murine bone defect model, 3 min USW treatment significantly improved bone regeneration (35.2 ± 3.8% increase in BV/TV, P < 0.01) and induced a 42% reduction in fibrosis versus controls. In vitro, USW enhanced JBMMSCs proliferation (2.1-fold increase in Ki67 + cells) and osteogenesis (3.5-fold higher ALP activity; 4.2- and 3.8-fold upregulation of RUNX2 and OCN expression). RNA-seq identified 141 differentially expressed genes, with phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling as the most enriched pathway (FDR < 0.01). Functional annotation of these transcriptomic alterations highlighted significant enrichment in cytokine responses and GTPase activity, suggesting that USW drives JBMMSC osteogenesis through the transcriptional modulation of the PI3K/Akt and JAK-STAT signaling networks These findings demonstrate USW therapy possibly promotes mandibular repair through JBMMSCs activity increase by regulating the gene expressions involved in the PI3K/Akt signaling pathway, with 3 min exposure being optimal. This study offers both theoretical insights and clinical rationale for USW-based maxillofacial bone regeneration strategies.

Glioblastoma therapy is severely limited by poor blood-brain barrier (BBB) penetration and systemic toxicity of chemotherapeutics. Here, we engineered polyphenol-stabilized selenium nanoparticles (nGPSe NPs, <60 nm) via spatial confinement synthesis as a redox-dual nanocatalytic carrier for afatinib (AFA). These AFA@nGPSe NPs utilize their distinct physicochemical properties to facilitate efficient nose-to-brain delivery, achieving high tumor accumulation while bypassing the BBB. The platform exhibits unique tumor-selective redox duality by generating cytotoxic reactive oxygen species and depleting glutathione within the tumors, yet activating antioxidant defense pathways in normal neural tissues to prevent neurotoxicity. This dual mechanism synergizes with AFA-induced tumor cell death. In orthotopic glioblastoma models, intranasal administration achieved a 60% long-term survival rate, driven by a chemoimmunotherapeutic response involving robust CD8+ T cell and macrophage infiltration. This study presents a multifunctional nanoplatform that integrates tumor microenvironment-responsive catalysis, non-invasive delivery, and immune reprogramming for precise and safe glioblastoma therapy.

BACKGROUND:Gliomas, particularly glioblastoma, remain difficult to control because diffuse infiltration into surrounding brain tissue limits complete resection and contributes to recurrence. Cannabidiol (CBD), a nonpsychoactive cannabinoid capable of entering the central nervous system, has shown antitumor activity in glioma models, but the mechanisms underlying its anti-invasive effects remain unclear. Lysyl oxidase-like 2 (LOXL2) regulates extracellular-matrix remodeling and mesenchymal phenotypes in several cancers. We therefore tested the hypothesis that CBD limits glioma growth and invasion partly by suppressing an LOXL2-associated extracellular-matrix and EMT-like program. METHODS:Human U87 and murine GL261 glioma cells were used to examine CBD effects on tetrazolium-based cell viability, clonogenic growth, cell-cycle progression, apoptosis, migration, and invasion. The two cell lines provided complementary human and murine models, and the immunocompetent intracranial GL261 model enabled syngeneic in vivo validation. RNA sequencing and public glioma datasets were used to identify and contextualize CBD-responsive molecules. Mechanistic involvement was tested by determining whether LOXL2 knockdown phenocopied and LOXL2 overexpression attenuated the anti-invasive effects of CBD. RESULTS:CBD reduced glioma-cell viability and clonogenicity, induced G1-phase arrest and apoptosis, and suppressed migration and invasion. C CCK-8-derived IC50 values (mean ± SD, n = 3) at 24, 48, and 72 h were 36.5 ± 0.3, 26.7 ± 0.3, and 21.4 ± 0.3 μM in U87 cells and 33.3 ± 0.2, 29.3 ± 0.2, and 25.5 ± 0.4 μM in GL261 cells, respectively. CBD treatment was accompanied by reduced MMP2 and MMP9 expression and increased TIMP3 expression. Transcriptomic profiling identified LOXL2 as a prominent CBD-downregulated molecule, and public datasets associated higher LOXL2 expression with aggressive molecular features and shorter overall survival. LOXL2 silencing reproduced the antimigratory and anti-invasive phenotype, whereas LOXL2 overexpression enhanced cell motility and partially attenuated the effects of CBD. The partial rescue involved vimentin, MMP9/TIMP3, EMT-related transcription factors, and F-actin-rich protrusions. In vivo, CBD reduced intracranial tumor burden and produced tissue changes consistent with lower proliferation, enhanced apoptosis, and suppression of the LOXL2-associated mesenchymal program. CONCLUSIONS:CBD suppresses glioma growth and limits invasion, at least in part, by attenuating an LOXL2-associated EMT-like and extracellular-matrix-remodeling program. Because LOXL2 overexpression produced only a partial rescue and direct target engagement was not tested, LOXL2 should be interpreted as a functional mediator rather than the sole or direct molecular target of CBD. These findings support further validation in patient-derived and pharmacokinetically informed glioma models.

Introduction and aims: The regeneration and repair of maxillofacial bone defects remain a significant clinical challenge. Jaw marrow-derived mesenchymal stem cells (JMMSCs) have attracted considerable attention owing to their favourable biological properties; however, the low survival rate of transplanted MSCs in vivo has substantially limited their therapeutic application. In this study, we demonstrate that hypoxic preconditioning enhances both the osteogenic and angiogenic potential of JMMSCs in vitro and in vivo. Methods: In vitro, the expression levels of osteogenic and angiogenic-related genes were assessed via qRT-PCR and Western blot following hypoxic preconditioning. In vivo, the impact of hypoxic preconditioning on the bone defect repair capacity of JMMSCs was evaluated. Micro–CT scanning was employed to compare microstructural changes at the defect sites. Microarray analysis identified differentially expressed long noncoding RNAs (lncRNAs) in JMMSCs subjected to hypoxic preconditioning. Subsequent bioinformatics analysis was conducted to explore potential regulatory interactions and key signalling pathways among lncRNAs, miRNAs, and mRNAs, followed by experimental validation. Results: Microarray analysis revealed a significant upregulation of lnc-4632427E13Rik in JMMSCs following hypoxic preconditioning. Mechanistic studies demonstrated that lnc-4632427E13Rik functions as a molecular ‘sponge’ by sequestering miR-34a-5p, leading to activation of the Aldoa/ERK/Hif-1α signalling axis and subsequent promotion of both angiogenesis and osteogenesis in JMMSCs. Conclusion: Our findings reveal hypoxic preconditioning as a highly effective strategy for enhancing the differentiation potential of JMMSCs, and further highlight the therapeutic potential of targeting the lnc-4632427E13Rik/miR-34a-5p/Aldoa axis to improve the bone repair capacity of JMMSCs. Clinical relevance: The lnc-4632427E13Rik/miR-34a-5p/Aldoa axis significantly enhances the efficiency and reliability of bone regeneration, representing a promising therapeutic target for clinical applications in the repair of maxillofacial bone defects.

Initial investigations established osteocalcin (OCN) as a pivotal factor in bone formation. Fully carboxylated osteocalcin (cOCN) exhibits a high affinity for hydroxyapatite within the bone matrix, yet under specific physiological conditions, it may undergo decarboxylation, thereby acquiring endocrine regulatory capabilities. Recent findings suggest a potential protective role for undercarboxylated osteocalcin (ucOCN) beyond bone, influencing various systems, including the brain, pancreas, muscle, and gonads, where its effects are well established. Although increased intracellular OCN expression is often considered a marker of osteoarthritis (OA) and chondrocyte hypertrophy, the specific role of extracellular ucOCN in chondrocytes remains largely unexplored and has received little attention, especially regarding its potential to modulate OA-related changes. This study used OCN knockout (OCN-/-) mice and found that OCN absence increased collagen type X (COL10) and matrix metalloproteinase 13 (MMP13) expression in chondrocytes, despite a lack of severe OA phenotype. A declining trend of ucOCN in synovial fluid was observed in arthritis models and OA patients, suggesting a role in OA progression. Elevation of ucOCN levels led to the downregulation of COL10a1 and MMP13 expression, accompanied by a marked improvement in cartilage integrity in murine models of arthritis. Additionally, ucOCN regulated the G protein-coupled receptor class C group 6 member A (GPRC6 A) and Hypoxia-inducible factor 1-alpha (HIF-1α) pathways, promoting TIMP3 expression and autophagy in chondrocytes, indicating distinct molecular mechanisms behind its protective effects.

Background and purposeStudies have shown that inflammation is a key risk factor for altitude sickness in hypobaric hypoxia environments. Periodontitis, a common oral disease, is prevalent among many individuals. This study aimed to investigate the onset and progression of neuroinflammation in mice with ligature-induced periodontitis under hypobaric hypoxia and to explore the potential underlying mechanisms.MethodsC57BL/6J mice were randomly divided into four groups: control (Con), hypobaric hypoxia (HH), periodontitis (P), and periodontitis combined with hypobaric hypoxia (PHH), which were then placed in a hypobaric hypoxia chamber for 1, 3, and 5 days. The expression of inflammatory cytokines was assessed by qPCR or ELISA. Anxiety-related behavior and memory abilities were evaluated by behavioral tests. The activation of microglia and astrocytes in the hippocampus and cortex was assessed by immunofluorescence.ResultsOur results demonstrated that one day of exposure to hypobaric hypoxia in mice with periodontitis significantly exacerbated periodontal inflammation, peripheral inflammation, and neuroinflammation. Specifically, hippocampal microglia in these mice were activated following brief exposure to hypobaric hypoxia. Furthermore, the STAT3 signaling pathway was markedly activated, playing a crucial role in mediating the intensified neuroinflammation observed in periodontitis model mice subjected to one day of hypobaric hypoxia.ConclusionOur data highlight the exacerbating effect of hypobaric hypoxia on neuroinflammation in periodontitis model mice, mediated through the activation of the STAT3 signaling pathway. These findings provide important insights and considerations for individuals with periodontitis who are planning to travel to high-altitude regions.

Photobiomodulation (PBM) utilizing 1064 nm near-infrared light, renowned for its deep tissue penetration capabilities, has demonstrated significant therapeutic potential in addressing brain disorders; however, its specific effects and underlying mechanisms in traumatic brain injury (TBI) remain poorly understood. This study investigated the therapeutic efficacy of 1064 nm light-emitting diodes (LED) treatment on emotional and cognitive impairments in a murine TBI model, and elucidating potential molecular mechanisms. C57BL/6 mice were systematically allocated into Sham, TBI, and TBI + PBM intervention groups, with the latter receiving daily 1064 nm light treatment (25 mW/cm2, 12 min/day) for 14 consecutive days post-TBI induction. Comprehensive behavioral assessments were conducted to evaluate emotional and cognitive functions. Advanced molecular analyses encompassing transcriptome sequencing, immunofluorescence, quantitative RT-PCR, and Western blot were employed to examine brain tissue damage, neurogenesis, synaptic remodeling, and inflammatory responses. The 1064 nm LED treatment demonstrated remarkable therapeutic effects, significantly ameliorating anxiety, depression-like behaviors, and spatial cognitive deficits in TBI mice. Behavioral improvements were evidenced by enhanced rotarod performance, increased exploratory behavior in open field and elevated plus maze tests, and improved Y-maze alternation rates. At the molecular level, PBM intervention exhibited multifaceted neuroprotective effects, including inhibition of neuronal apoptosis, reduction of brain injury, promotion of neurogenesis and synaptic remodeling, and upregulation of neurotrophic factors. Furthermore, the treatment enhanced blood–brain barrier integrity through upregulation of tight junction proteins and modulated neuroinflammation by shifting microglia and astrocytes toward anti-inflammatory phenotypes. These findings collectively demonstrate that 1064 nm wavelength PBM treatment effectively promotes functional recovery and mitigates both emotional and cognitive impairments in TBI mice, providing novel mechanistic insights and a promising wavelength option for PBM-based therapeutic strategies in TBI management.

Circadian rhythm abnormalities due to sleep deprivation (SD) may promote the development of emotional and cognitive disorders. Though light therapies have been employed to treat circadian disorders, the exact treatments and their underlying biology are still unclear. Our study aimed to investigate the effects of intrinsically photosensitive retinal ganglion cells (ipRGCs) sensitive 480 nm blue light on circadian rhythms affecting emotional and cognitive behaviors and the expression of neural stem cells (NSCs) stemness genes. In this study, we demonstrate that for mice with acute SD for 24 h, exposure to ipRGCs sensitive 480 nm blue light at ~ 1300 lux for 30 min at 8:00 a.m. and 8:00 p.m. improves the stability of disrupted clock genes, increases nocturnal activity, reduces anxiety-like behaviors, and enhances cognitive abilities. Furthermore, 480 nm blue light exposure reduces fluctuations in NSCs stemness gene expression induced by SD, potentially through its effect on enhancing the amplitude of suprachiasmatic nucleus (SCN) circadian oscillations. These findings may provide novel strategy for alleviating rotating circadian rhythm-related anxiety and learning and cognitive obstruction.

Depression involves abnormal neural oscillations. Photobiomodulation (PBM) modulates such oscillations but lacks behavioral electrophysiological mechanistic studies. We explored PBM’s effects on hippocampal CA1 oscillations and phase-amplitude coupling (PAC) in a depression model. Male C57BL/6J mice were randomly divided into saline, LPS (2 mg/kg i.p.), and LPS + PBM groups (n = 10/group for behavioral tests, n = 8/group for electrophysiology). LPS groups received lipopolysaccharide to induce neuroinflammation. The LPS + PBM group underwent 810 nm PBM (20 mW/cm², 12 min/day × 4 days) starting day 4 post-injection. Anxiety- and depression-like behaviors were assessed via open field, elevated plus-maze, and tail suspension tests. Wireless electrophysiology recorded CA1 local field potentials (LFP) during rest and behaviors. Oscillations and PAC were analyzed. Data are presented as mean ± SD; group differences were evaluated by one-way ANOVA with Bonferroni post-hoc correction and ɳ² effect sizes, with two-tailed p < 0.05 taken as statistically significant. PBM (20 mW/cm2) alleviated LPS-induced anxiety and depressive behaviors. Electrophysiologically, PBM restored resting-state δ power (LPS + PBM: 0.0499 ± 0.0282, LPS: 0.1491 ± 0.0887; p < 0.01) and enhanced δ-γ coupling (LPS + PBM: 2.049 ± 0.447, LPS: 0.230 ± 0.298; p < 0.05). During anxiety tasks, PBM suppressed γ power (LPS + PBM: 0.3709 ± 0.1569, LPS: 0.5165 ± 0.06896; p < 0.05) and strengthened δ-γ PAC (LPS + PBM: 0.741 ± 0.508 vs. LPS: 0.217 ± 0.218, p < 0.05). In depression tests, PBM normalized δ power (LPS + PBM: 0.0261 ± 0.0182, LPS: 0.1315 ± 0.0619; p < 0.001) and reduced γ power (LPS + PBM: 0.2848 ± 0.0921, LPS: 0.4067 ± 0.0892; p < 0.05). No significant PAC changes was observed during depression tasks. PBM therapy ameliorates LPS-induced depression and anxiety behaviors while normalizing hippocampal CA1 oscillations and cross-frequency coupling. Its effects are state-dependent, modulating distinct frequency bands and PAC across rest and behavioral contexts, revealing potential electrophysiological therapeutic mechanisms.

The 3D human pituitary organoid represents a promising laboratory model for investigating human pituitary diseases. Nonetheless, this technology is still in its nascent stage, with uncertainties regarding the cellular composition, intercellular interactions, and spatial distribution of the human pituitary organoids. To address these gaps, the culture conditions are systematically adjusted and the efficiency of induced pluripotent stem cells' (iPSCs') differentiation into pituitary organoids is successfully improved, achieving results comparable to or exceeding those of previous studies. Additionally, single-cell RNA-sequencing (scRNA-seq) and stereomics sequencing (Stereo-seq) are performed on the pituitary organoids for the first time, and unveil the diverse cell clusters, intricate intercellular interactions, and spatial information within the organoids. Furthermore, the SOX3 gene interference impedes the iPSCs' differentiation into pituitary organoids, thereby highlighting the potential of pituitary organoids as an ideal experimental model. Altogether, the research provides an optimized protocol for the human pituitary organoid culture and a valuable transcriptomic dataset for future explorations, laying the foundation for subsequent research in the field of pituitary organoids or pituitary diseases.

Major depressive disorder (MDD) is a major global mental concern that severely affects quality of life, yet current pharmacological treatments remain limited in their effectiveness. Long-term chronic stress has been shown to increase the incidence of depression and anxiety. Micro RNAs (miRNAs) have been revealed to participate in the pathological process of depression and represent promising therapeutic targets. In this study, we found that microRNA-129-5p (miR-129-5p) was significantly decreased in the brains of depressive mice. Overexpression of miR-129-5p in the hippocampus effectively alleviated depressive-like behaviors and reduced the activation of microglial cells and astrocytes. In addition, ATP levels in depressive mice were significantly increased following miR-129-5p overexpression. The antidepressant effects of miR-129-5p were reversed when ATP function was blocked with the non-specific P2 receptor antagonist suramin. In vitro experiments revealed that miR-129-5p overexpression enhanced ATP production in astrocytes. Furthermore, using a dual-luciferase reporter assay, we found that miR-129-5p directly targeted Mysm1. When overexpressed in astrocytes, miR-129-5p significantly suppressed Mysm1 expression, promoted phosphorylation of p53 and AMPK, and enhanced the expression of PGC1α, factors previously associated with ATP production. Our findings highlight the crucial role of miR-129-5p in regulating depression, suggesting that miR-129-5p overexpression may serve as an effective strategy for antidepressant treatment.

BACKGROUND:Hypobaric hypoxia exposure (HHE) often causes neuropsychiatric disorders. Due to its complex mechanism, efficient strategies for alleviating HHE-induced anxiety- and depression-like behaviors remain limited. AIM:To characterize alterations in the oral and gut microbiota following HHE and to explore a potential microbiota-based intervention to mitigate associated psychiatric symptoms. METHODS:C57BL/6J mice were exposed to simulated high-altitude hypoxia (5000 m) for 1, 3, 5, or 7 days. Behavioral assessments, including the open field test, elevated plus maze, and forced swim test, were conducted to evaluate anxiety- and depression-like behaviors. Oral and fecal microbiota were analyzed using 16S rRNA sequencing to assess changes in microbial composition and diversity. Immunofluorescence staining was performed to examine c-Fos expression in brain nuclei. A probiotic formulation containing Lactobacillus rhamnosus (L. rhamnosus) DSM17648, Lactobacillus acidophilus DDS-1, and L. rhamnosus UALR-06 was administered to mice subjected to one day of HHE (HH1) to evaluate its therapeutic efficacy. RESULTS:Behavioral tests revealed that HHE caused anxiety- and depression-like behaviors, which were most pronounced after 1 day of exposure. The IF data revealed significantly increased expression of c-Fos in various brain nuclei after HHE, including the anterior cingulate cortex, paraventricular thalamic nucleus, lateral habenula nucleus, paraventricular hypothalamic nucleus, lateral hypothalamus, and periaqueductal gray. The 16S rRNA sequencing results demonstrated a sharp decline in the abundance of Lactobacillus in the oral microbiota of mice exposed to HH1 and a marked decrease in the abundance of Lactobacillus and Bifidobacterium in the fecal microbiota of mice exposed to three days of HHE. Finally, oral administration and gavage of Lactobacillus significantly alleviated anxiety- and depression-like behaviors in HH1 mice. CONCLUSION:HHE caused significant variations in the oral and fecal microbiota of mice. Lactobacillus supplementation alleviated anxiety- and depression-like behaviors in mice. Improving oral flora may relieve HHE-induced psychiatric disorders.

Background Subjective tinnitus is an auditory perception occurring without an external sound source. The medial geniculate body (MGB) plays a critical role in tinnitus pathology. The order of this study is to investigate whether mid-infrared (MIR) modulation of the MGB can mitigate tinnitus-like behavior in mice.Methods RNA sequencing was employed to analyze and compare gene expression levels in the MGB of mice with tinnitus to those of control mice. Golgi staining and transmission electron microscopy were used to confirm alterations in the structural plasticity of neurons. The whole-cell patch-clamp technique was applied to assess changes in neuronal functional plasticity. MIR optical fibers were employed to modulate MGB neuronal activity. Molecular dynamics simulations were performed to investigate the regulatory effect of MIR on hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channel function.Results The results of this study illustrates that MIR modulation reversed the abnormal electrophysiological properties of neurons associated with tinnitus-like behavior. Furthermore, molecular dynamics simulations revealed that MIR regulates HCN channel function, reducing the increased firing frequency of MGB neurons in tinnitus mice.Conclusions MIR intervention may alleviate the abnormal increase in neuronal firing frequency in the MGB of tinnitus mice by modulating HCN channel function. This regulatory mechanism involves influencing the secondary structure of HCN channels, enhancing hyperpolarization-activated current amplitude, and restoring reduced amplitudes observed in tinnitus mice.

Diabetes-associated periodontitis and cognitive dysfunction form a vicious cycle that impairs tissue repair. Polyphenol-engineered artificial nanoprobiotics using ultrasound-responsive dihydrocaffeic acid (DA)-mediated Fe/Zn bimetallic porphyrin MOFs (Fe-TCPP-DA-Zn), integrated into adaptive hydrogels, is developed. This design enables microenvironment-responsive antibacterial action through enhanced sonodynamic performance via bandgap reduction, while DA simultaneously restores oral microbiota balance. Zinc ions coordinate dual-function bone regulation by inhibiting osteoclasts and activating osteoblasts. Single-cell analysis reveals macrophage-fibroblast crosstalk as the regeneration driver in diabetic periodontitis. The hydrogel system demonstrates bidirectional therapeutic effects, promoting periodontal soft/hard tissue reconstruction while alleviating anxiety-like behaviors through oral-brain axis modulation. The findings propose an antioxidant nanoprobiotic strategy to break the oral-systemic disease cycle, providing new insights into microbiome-brain interactions.

Despite growing treatments for traumatic brain injury, there is still no ideal strategy for efficiently mitigating these processes. Ultrashort wave therapy, a type of physical factor therapy, has been widely used in various clinical treatments. However, its effects on traumatic brain injury and the underlying mechanisms are not well understood. In this study, we demonstrate that ultrashort wave treatment can significantly promote injury repair and alleviate emotional and cognitive disorders. Our data showed that ultrashort wave reduced the levels of pro-inflammatory factors and inhibited neuroinflammation. In vitro experiments showed that ultrashort wave inhibited activation of C8-D1A astrocytes and BV2 microglia. Furthermore, traumatic brain injury induced the expression of Piezo1, while ultrashort wave effectively suppressed this high expression. Administration of Yoda1, a Piezo1 agonist, to traumatic brain injury mice reversed the beneficial effects of ultrashort wave. Consistently, Yoda1 also reversed the inhibitory effect of ultrashort wave on activation of C8-D1A astrocytes. These findings indicate that ultrashort wave is an ideal therapeutic strategy for traumatic brain injury, which works by inhibiting Piezo1, reducing neuroinflammation, and promoting nerve repair after traumatic brain injury.

BackgroundPrimary central nervous system germ cell tumors (CNS GCTs) are rare intracranial malignancies, and their tumor microenvironment plays a crucial role in tumor initiation and progression. However, the specific characteristics of the immune microenvironment and their clinical significance remain poorly understood.MethodsThis study included 93 paraffin-embedded tissue samples from 90 patients diagnosed with CNS GCTs. Immunohistochemistry and immunofluorescence staining were used to assess the infiltration patterns of T cell subsets (CD3+, CD4+, CD8+, Foxp3+) and the expression levels of immune checkpoints (CTLA-4, PD-1, PD-L1). Additionally, the study explored the relationship between these immune features and the patient’s clinical characteristics and prognosis.ResultsThe study revealed that germinomas exhibited significantly higher infiltration of CD4+ and Foxp3+ T cells compared to non-germinomatous GCTs (NGGCTs). Additionally, CTLA-4 expression was detected in 58.06% of cases, while PD-1 and PD-L1 were expressed in over 90%, with higher CTLA-4 levels in germinomas and elevated PD-L1 levels in NGGCTs. T cell infiltration was positively correlated with immune checkpoint expression, particularly in germinomas. The results also highlighted the strong immunosuppressive nature of the CNS GCTs’ tumor microenvironment. Furthermore, T cell infiltration and immune checkpoint expression were closely associated with clinical characteristics and prognosis. Notably, PD-1 expression was identified as an independent prognostic factor for progression-free survival (PFS) and recurrence-free survival (RFS).ConclusionOur study highlighted the distinct characteristics of T cell infiltration and the significant expression of immune checkpoints in CNS GCTs, revealing the highly heterogeneous and immunosuppressive nature of the tumor microenvironment. PD-1 expression was identified as an independent prognostic predictor, offering a foundation for enhancing risk stratification in CNS GCT patients. These findings also support the potential for future clinical applications of immune checkpoint inhibitors, such as PD-1 monoclonal antibodies.

BackgroundPituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations across multiple systems. These include lifelong infertility, short stature, mental retardation, and potentially life-threatening pituitary crises if not promptly diagnosed and treated. Despite extensive research, the precise pathogenesis of PSIS remains unclear. Currently, there are two proposed theories regarding the pathogenic mechanisms: the genetic defect theory and the perinatal injury theory.MethodsWe systematically searched English databases (PubMed, Web of Science, Embase) and Chinese databases (CNKI, WanFang Med Online, Sinomed) up to February 24, 2023, to summarize studies on gene sequencing in PSIS patients. Enrichment analyses of reported mutated genes were subsequently performed using the Metascape platform.ResultsOur study included 37 articles. KEGG enrichment analysis revealed mutated genes were enriched in the Notch signaling pathway, Wnt signaling pathway, and Hedgehog signaling pathway. GO enrichment analysis demonstrated mutated genes were enriched in biological processes such as embryonic development, brain development, axon development and guidance, and development of other organs.ConclusionBased on our summary and analyses, we propose a new hypothesis: disruptions in normal embryonic development, partially stemming from the genetic background and/or specific gene mutations in individuals, may increase the likelihood of abnormal fetal deliveries, where different degrees of traction during delivery may lead to different levels of pituitary stalk interruption and posterior lobe ectopia. The clinical diversity observed in PSIS patients may result from a combination of genetic background, specific mutations, and variable degrees of traction during delivery.

Depression is a mental disease that involves a variety of complex physiological mechanisms. A wide range of methods have therefore been used to establish mouse models of depression, and there are currently many ways to develop such mouse models. The present study aimed to compare the effects of various model induction methods and assesses their different effects. To this end, C57BL/6J mice were divided into three experimental groups: the chronic restraint stress (CRS) group received 6 hours of daily confinement within restraint tubes over a 3-week period; the chronic lipopolysaccharide (C-LPS) administration group received daily intraperitoneal injections of 0.5 mg/kg LPS for 1 week; and the acute LPS (A-LPS) administration group received a singular intraperitoneal injection of 0.83 mg/kg LPS. A corresponding control group was established for each experimental condition. Following mouse model establishment, depression-like behaviors were assessed through the forced swimming and tail suspension tests; anxiety-related behaviors were evaluated using the open field test and elevated plus maze. Furthermore, the expression of the immediate early gene c-Fos, ionized calcium-binding adapter molecule 1 (IBA1), and glial fibrillary acidic protein (GFAP) was examined via immunofluorescence. Longer immobility durations during the forced swimming and tail suspension tests were observed across all model groups (p < 0.05), indicating depression-like behaviors. Furthermore, the CRS and C-LPS group, but not the A-LPS group, showed significant anxiety-like behaviors in the elevated plus maze (p < 0.05). All model groups also exhibited significant increases in both time and distance explored within the central area of the open field test (p < 0.05). The activation of GFAP- and IBA1-positive cells in the cerebral cortex and hippocampus was also markedly pronounced in all experimental groups, suggesting the association of neuroinflammatory responses with induced depressive states. The present findings contribute to our understanding of the pathophysiology of stress-induced and neuroinflammatory-associated depression, and will help researchers to choose suitable depression models for their investigations.