Neurosyphilis is an infectious disease of the nervous system caused by Treponema pallidum. With the resurgence of syphilis worldwide, neurosyphilis has become prevalent again, but research on its pathogenesis remains challenging. T. pallidum exhibits remarkable invasive potential and immune evasion properties, which enable it to rapidly penetrate the blood-brain barrier (BBB) and infiltrate the central nervous system. Meanwhile, the immune response induced by this pathogen may cause tissue damage and accelerate disease progression. Additionally, host factors and the genotypes of T. pallidum strains are associated with susceptibility to neurosyphilis. This review systematically summarizes the latest literature on neurosyphilis, outlines recent advances in research on the effects of T. pallidum on the BBB, its immune interactions with the host, and omics-related studies, and aims to provide directions for future research on the pathogenesis of neurosyphilis.

Introduction and importance: While cefepime-induced neurotoxicity is a known complication of beta-lactam therapy in renal impairment, its diagnosis is uniquely challenging in patients with complex neurosurgical baselines. This case illustrates the risk of diagnostic anchoring where the presence of a ventriculoperitoneal shunt diverts clinical suspicion toward mechanical failure and obscures a reversible toxic etiology. Case presentation: A 63-year-old female with subarachnoid hemorrhage, slit ventricle syndrome, and a ventriculoperitoneal shunt presented with septic shock and acute kidney injury. Following renal adjustment of cefepime for Pseudomonas bacteremia, she developed profound altered mental status. Initial evaluation prioritized shunt malfunction, yet computed tomography was confounded by chronic slit ventricle physiology. Electroencephalography revealed generalized triphasic waves characteristic of metabolic encephalopathy rather than structural dysfunction. Clinical discussion: Cefepime-induced neurotoxicity (CIN) pathophysiology involves gamma-aminobutyric acid-A receptor inhibition amplified by reduced renal clearance and sepsis-induced blood–brain barrier disruption. Here, the clinical picture was masked by the overlap between toxic encephalopathy and insidious shunt failure symptoms. This necessitated distinguishing toxicity from nonconvulsive status epilepticus or hydrocephalus using electroencephalogram (EEG), defying the heuristic that neurological decline in shunted patients is mechanical until proven otherwise. Conclusion: This case underscores that CIN can mimic mechanical shunt failure, which necessitates a high index of suspicion in patients with indwelling neurosurgical hardware. Early EEG utilization is critical to overcome diagnostic bias and ensure prompt antibiotic discontinuation rather than unnecessary neurosurgical intervention.

Objective: This study compares the brain protective effects of L-borneolum and its main components (a combined application of L-borneol and L-camphor) on the rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). It also makes clear the intrinsic regulatory mechanisms that link the neuroprotective effects of these compounds on IS to the blood-brain barrier (BBB), based on network pharmacology predictions. Furthermore, the study investigates the relationship between these compounds and the Major Facilitator Superfamily Domain-containing Protein 2A (MFSD2A)/Caveolin-1 (Cav-1) signaling axis. Methods: The MCAO/R model in rats was established to evaluate the therapeutic effect of L-borneolum (200 mg/kg) and its main components combination of L-borneol and L-camphor (6:4 ratio, 200 mg/kg). Neurological scores, 2,3,5-triphenyl tetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and Nissl staining were performed to evaluate the neurological damage in the rats. Cerebral blood flow Doppler was applied to monitor the cerebral blood flow changes. Immunofluorescence analysis of albumin leakage and transmission electron microscopy (TEM) were conducted to evaluate blood-brain barrier (BBB) integrity. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the optimal drug concentration. Trans-epithelial electrical resistance (TEER) and horseradish peroxidase (HRP) assays were employed to confirm the successful establishment of an in vitro BBB co-culture model. Network pharmacology was utilized to predict the biological processes, molecular functions, and cellular components involved in the treatment of ischemic stroke (IS) by the main components of L-borneolum (L-borneol and L-camphor). Finally, immunofluorescence, real-time fluorescent quantitative PCR (RT-qPCR) and western blot analyses were performed to detect the expression of Major Facilitator Superfamily Domain Containing 2A (MFSD2A), caveolin-1 (CAV-1), sterol regulatory element-binding protein 1 (SREBP1) in brain tissue and hCMEC/D3 cells. Results: Network pharmacology prediction indicated that L-borneolum and its main components (L-borneol and L-camphor) in the treatment of IS are likely associated with vesicle transport and neuroprotection. Treatment of IS with L-borneolum and its main components significantly decreased neurological function scores and cerebral infarction area, while alleviating pathological morphological changes and increasing the number of Nissl bodies in the hippocampus. Additionally, it improved cerebral blood flow, reduced albumin leakage, and decreased vesicle counts in the brain. The trans-epithelial electrical resistance (TEER) of the co-culture model stabilized on the fifth day after co-culture, and the permeability to horseradish peroxidase (HRP) in the co-culture model was significantly lower than that of the blank chamber at this time. RT-qPCR and Western blot results demonstrated that, compared to the model group, the expression of SREBP1 and MFSD2A significantly increased, while the expression of Cav-1 decreased. Conclusions: L-borneolum and its main components combination (L-borneol/L-camphor, 6:4 ratio) may exert a protective effect in rats with IS by improving BBB transport function through modulation of the MFSD2A/Cav-1 signaling pathway.

Blood-brain barrier (BBB) disruption is a recognized contributor to neurodegenerative diseases. However, its specific role in cognitive decline in diabetes has not been sufficiently explored. This study aimed to evaluate the association between BBB integrity and cognitive function and to investigate the discriminative ability of BBB-related biomarkers for cognitive impairment in individuals with type 2 diabetes mellitus (T2DM). In this case-control study, participants were recruited from the Second Affiliated Hospital of Nanchang University. All subjects underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We compared quantitative brain imaging (Ktrans and Ve) and serum platelet-derived growth factor receptor β (PDGFRβ) between diabetic individuals with and without cognitive impairment. The relationships between these biomarkers and cognitive performance were assessed using linear regression analyses. The discriminative capacity of each biomarker for distinguishing groups was evaluated using receiver operating characteristic (ROC) curve analysis. T2DM individuals with cognitive impairment exhibited significantly elevated Ktrans and Ve levels compared to those without, which correlated inversely with MoCA scores in key brain regions. Serum PDGFRβ was also independently associated with impaired cognition. Every biomarker individually demonstrated high discriminative power for evaluating cognitive status, with AUC values of 0.908 (95% CI: 0.842 to 0.973) for Ktrans, 0.923 (95% CI: 0.86 to 0.986) for Ve, and 0.839 (95% CI: 0.751 to 0.928) for PDGFRβ. Our results confirm the critical role of BBB dysfunction in diabetic cognitive impairment. The biomarkers serum PDGFRβ, Ktrans, and Ve showed potential associations with this condition, suggesting their clinical value for future clinical application in risk stratification and therapeutic monitoring in T2DM population. TRN: ChiCTR2400085417, 2024.06.06, retrospectively registered.

Enhancing antibody exposure within the central nervous system (CNS) is critical for developing therapeutic monoclonal antibodies (Mabs) to treat CNS disorders. However, limited antibody penetration across the blood-brain barrier (BBB) and rapid efflux from the cerebrospinal fluid hinder effective CNS delivery. While most research efforts focus on enhancing the permeation of antibodies across the BBB, here we present an alternative strategy to enhance antibody retention by directly binding hyaluronic acid (HA) in the brain's extracellular space. To accomplish this, we fused the G1 domain of versican (VG1), a proteoglycan known for HA binding, with nontargeting Fab and Mab (IgG) antibodies. Using single-photon emission computed tomography/X-ray computed tomography imaging, we tracked the biodistribution of 125I-labeled Fab- and Mab-(VG1)2 fusion constructs, as well as their parent antibodies, after direct infusion into the lateral ventricles of cannulated mice. Over 96 h, both VG1 constructs significantly enhanced antibody exposure in the brain and spine compared to the parent antibodies. Fab-VG1 exhibited a more widespread brain distribution, while Mab-(VG1)2 was localized around the administration site. Fluorescence microscopy demonstrated periventricular distribution of antibody with a greater depth of infiltration for Fab-VG1 across all ventricles at 1 and 96 h time points compared to Mab-(VG1)2. Escalating the dose of Fab-VG1 enhanced tissue penetration distance. These findings demonstrate the feasibility of using HA-binding technology to enhance antibody exposure in the CNS, offering potential for the development of more effective antibody-based therapies for CNS disorders.

Brain pericytes play essential roles in vascular homeostasis, including capillary stabilization and maintenance of the blood–brain barrier. Lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, is known to trigger inflammatory responses not only systemically but also within the central nervous system. In this study, we investigated the effects of LPS on the phenotype and transcriptome of brain vascular pericytes. LPS promoted bromodeoxyuridine incorporation in the primary culture of human brain pericytes as well as increased the number of Ki67-positive cells, indicating enhanced pericyte proliferation. Morphological analysis revealed that LPS decreased the cellular aspect ratio, suggesting altered cellular elongation. Transcriptomic profiling showed that LPS-induced differentially expressed genes were enriched for terms related to cell proliferation, angiogenesis, and blood–brain barrier function. Because pericytes critically regulate neurovascular coupling and metabolic support for active neurons, these LPS-induced alterations may ultimately perturb the microvascular control of neural circuits. These results suggest that LPS has the potential to regulate brain vascular function by inducing morphological and functional changes in pericytes.

Abstract Glioblastoma multiforme (GBM) is a highly aggressive type of brain cancer known for its rapid progression and treatment resistance, presenting significant challenges for effective management. This article examines the promising potential of mesoporous silica nanoparticles (MSNs) as a groundbreaking platform for both the treatment and diagnosis of this formidable disease. MSNs boast several advantageous properties, including a large surface area, customizable pore sizes, and excellent biocompatibility. These characteristics enable efficient encapsulation of therapeutic agents, controlled release, and targeted delivery directly to GBM cells. One of the key advantages of MSNs is their ability to be functionalized with specific targeting ligands, which enhances their specificity toward tumor cells, facilitates navigation through the blood–brain barrier (BBB), and helps address the issues of tumor heterogeneity and drug resistance. When integrated with multimodal therapies, such as chemotherapy, immunotherapy, and photodynamic therapy, MSNs can create synergistic effects that improve therapeutic outcomes while reducing adverse off-target effects. Additionally, MSNs are poised to enhance diagnostic capabilities, improving imaging techniques for the accurate detection and monitoring of GBM. This review consolidates recent advancements in MSN-based approaches, emphasizing their therapeutic and diagnostic potential while also discussing toxicity concerns and outlining future pathways for clinical application to ultimately enhance patient outcomes.

Stainless Steel-Synthesized gold Nanoparticles: Insights into Blood-Brain barrier permeability and microglial interaction.

Long COVID (LC) is a multisystem, post-infectious conditions diagnosed ≥3 months after acute SARS-CoV-2 infection and marked by relapsing, persistent, or progressive symptoms, especially fatigue, post-exertional symptom exacerbation and neuropsychiatric syndromes. We synthesized evidence suggesting that LC arises from intersecting pathways including viral persistence, intestinal dysbiosis and barrier compromise with microbial translocation, innate immune activation with neutrophil extracellular traps (NET) and thromboinflammation, and immune dysregulation with features of exhaustion and autoimmunity. These processes adversely impact blood-brain barrier (BBB) function and lead to neuroinflammation. We propose a mechanistic model in which viral antigens and translocated microbial products amplify pro-inflammatory networks promoting immunothrombosis and tissue hypoperfusion. Hematogenous and gut-brain pathways may then deliver inflammatory mediators to the central nervous system (CNS), resulting in BBB disruption and glial activation that underpin nervous system disorders in LC. Treatment regimens aimed at lowering antigen load, restoring mucosal barrier integrity and modulating myeloid/coagulation pathways may warrant investigation as novel therapeutic strategies to treat LC.

The gut microbiome produces thousands of metabolites with potential to modulate central nervous system function through peripheral or direct neural mechanisms. Tourette syndrome, attention-deficit/hyperactivity disorder, and autism spectrum disorder exhibit shared neurotransmitter dysregulation and microbiome alterations, yet mechanistic links between microbial metabolites and receptor-mediated neuromodulation remain unclear. We screened 27,642 microbiome SMILES metabolites for blood–brain barrier permeability using rule-based SwissADME classification and a PyTorch 2.0 neural network trained on 7807 experimental compounds (test accuracy 86.2%, AUC 0.912). SwissADME identified 1696 BBB-crossing metabolites following Lipinski’s criteria, while PyTorch classified 2484 metabolites with expanded physicochemical diversity. Following 3D conformational optimization (from SMILES) and curation based on ≤32 rotatable bonds, molecular docking was performed against five neurotransmitter receptors representing ionotropic (GABRA2, GRIA2, GRIN2B) and metabotropic (DRD4, HTR1A) receptor classes. The top 50 ligands across five receptors demonstrated method-specific BBB classification (44% SwissADME-only, 44% PyTorch-only, 12% overlap), validating complementary prediction approaches. Fungal metabolites from Ascomycota dominated high-affinity top ligands (66%) and menaquinone MK-7 showed broad phylogenetic conservation (71.4% of phylum). Our results establish detailed receptor–metabolite interaction maps, with fungal metabolites dominating high-affinity ligands, challenging the prevailing bacterial focus of the microbiome and providing a foundation for precision medicine and a framework for developing microbiome-targeted therapeutics to address clinical needs in neurodevelopmental disorders.

Epilepsy is a chronic neurological disorder characterized by abnormal, excessive, and synchronous firing of neurons in the brain. Numerous biological studies have shown that the seizure and progression of epilepsy can directly activate the ferroptosis pathway, leading to dysregulation of physiological signaling and the induction of oxidative stress. As a key member of the reactive oxygen species (ROS) family, O2•- plays an important regulatory and signaling role in the nervous system. Investigating the dynamic regulation of O2•- between epilepsy and the ferroptosis pathway is crucial. Thus, high-resolution specific imaging of O2•- in the brain is urgently needed. Regarding the issue of being susceptible to interference from other reactive oxygen species, we innovatively introduced a series of push-pull electron groups (-F, -Cl, -Br, -I, -OCH3, -CF3, -H) to adjust the activity of the trifluorosulfonic acid group. LYC-CF3 was founded to be specific for O2•-. Meanwhile, due to the isophorone fluorophore, the probe exhibits enhanced lipophilicity, red-shifted emission wavelengths, and the ability to cross the blood-brain barrier. Using LYC-CF3, we constructed a brain imaging epilepsy model under ferroptosis inducers and inhibitors as a marker for O2•-. For the first time, we revealed ferroptosis pathways mediating epilepsy. These findings provide a new theoretical basis and potential intervention strategy for the early diagnosis and treatment of epilepsy.

Objective . This study aimed to systematize and analyze contemporary data on the evolution of cephalosporin antibiotics from the first to the fifth generation, with a focus on changes in their antimicrobial spectrum, pharmacokinetic properties, and safety profile in the context of rising antibiotic resistance. Materials and methods . A review of the scientific literature was conducted, sourcing data from PubMed, Google Scholar, CyberLeninka, elibrary.ru, and library resources using keywords such as "cephalosporins", "antibiotic resistance", "MRSA", "Gram-negative bacteria", and "cefiderocol". The analysis included systematic reviews, randomized clinical trials, cohort studies, and meta-analyses published over the last two decades, as well as foundational historical works. Results . The review demonstrates a clear evolutionary trajectory in the development of cephalosporin. First- and second- generation agents remain relevant for treating infections caused by Gram-positive cocci and some communities of Gram-negative microorganisms. Third- and fourth-generation cephalosporins have become the cornerstone of empirical therapy for nosocomial infections because of their expanded spectrum of activity against Gram-negative flora, including Pseudomonas aeruginosa. Fifth-generation drugs (ceftobiprole and ceftaroline) were developed to overcome MRSA resistance. A separate analysis was dedicated to the innovative agent, cefiderocol — the first siderophore cephalosporin, which possesses a unique transport mechanism into the bacterial cell and demonstrates activity against carbapenem-resistant strains of Enterobacterales, P. aeruginosa, and A. baumannii. Despite its unique properties, cefiderocol resistance is already emerging. The specific pharmacokinetic profiles (administration routes, half-life, and blood-brain barrier penetration) and spectrum of adverse reactions (allergic, hematological, and neurological) of different generations were analyzed. Conclusion . Cephalosporins remain a cornerstone of modern antimicrobial therapy because of their favorable efficacy and safety profile. The introduction of new generations, particularly cefiderocol, represents a direct response to the global challenge of antibiotic resistance. However, the rapid emergence of resistance mechanisms even to the most advanced agents underscores the critical importance of antimicrobial stewardship programs and strict adherence to the principles of rational antibiotic therapy to preserve the future clinical value of this drug class.

Malignant tumors pose a public health challenge due to escalating incidence and mortality. Traditional treatments suffer from poor target specificity between healthy and tumor tissues, resulting in severe side effects. Immunotherapy is a pivotal advancement, but it faces poor tumor penetration, low targeting efficiency, inadequate drug delivery, immune evasion, and drug resistance. To overcome these challenges, ultrasound-mediated targeted micro/nanobubbles (UMT-MNBs) emerge, which is a noninvasive, highly targeted, and nonviral vector novel therapeutic method for malignant tumors. This approach overcomes drug resistance and facilitates the targeted release of therapeutic molecules. Concurrently, MNBs activate the immune system, enhance immune cell filtration, suppress tumor angiogenesis, and induce immunogenic cell death (ICD). UMT-MNBs demonstrate synergistic potential with conventional therapies, showcasing substantial clinical promise. This review presents recent advances in UMT-MNBs for drug/gene delivery, hypoxia modulation, resistance mitigation, immune activation/regulation, and penetration of blood-brain barrier. It also introduces UMT-MNBs in combinatorial regimens, including chemo, radio, photothermal, photodynamic, and sonodynamic therapies, to reduce dosage, improve efficacy, and minimize toxicity, thereby advancing precision medicine in oncology. Finally, future research on UMT-MNBs is discussed. It is necessary to focus on optimizing ultrasound parameters, emphasizing surface functionalization of MNBs, elucidating the mechanisms of immune activation and regulation, and exploring multimodal combined treatment strategies. Our findings provide new insights into the visualization and real-time regulation capabilities of UMT-MNBs, driving the application of immunotherapy and combination therapies, opening new directions for targeted therapy, and facilitating breakthrough progress in cancer therapy.

Medications known to cross the blood-brain barrier (psychotropic medications) are commonly prescribed to women during pregnancy, often for the management of mental illness. Although there is little evidence of gross neurological teratogenicity of any medication in current widespread use, a growing body of evidence from animal models, human magnetic resonance imaging and behavioural studies suggests that more subtle adverse effects on early life neurodevelopment may result from in utero psychotropic exposure. Understanding these consequences is of crucial importance as prescribing rates of psychotropic medication during pregnancy have increased rapidly in recent years. We review current studies directly quantifying early life brain correlates of exposure, discuss plausible mechanistic pathways and make suggestions for future research.

The hybrid marbled goby (Oxyeleotris marmoratus ♀ × Oxyeleotris lineolatus ♂) is a high-value aquaculture species in China, with rapidly increasing production in recent years. While Streptococcus agalactiae is a well-known pathogen in various fish species, its association with marbled goby has not been previously reported. Here, we present the first confirmed case of S. agalactiae infection in farmed hybrid marbled goby. Infected fish exhibited typical signs of streptococcosis, including erratic swimming, hemorrhages at fin bases, skin ulcers, and cloudy or hemorrhagic eyes. A Gram-positive bacterial strain, designated ZH2208, was isolated from diseased fish. Morphological, biochemical, 16S rRNA sequencing, and phylogenetic analyses identified the isolate as S. agalactiae, serotype Ia-a dominant serotype previously associated with tilapia infections in Guangdong, China. Challenge experiments using doses of 1 × 10⁴ and 1 × 10⁷ CFU/fish confirmed the high virulence of ZH2208, resulting in 50% and 100% mortality, respectively. Eleven virulence genes involved in host invasion, hemolysis, immune evasion, and blood-brain barrier penetration were detected by PCR. Histopathology revealed typical lesions in gills, liver, spleen, kidney, and brain, including acute inflammation, hemorrhage, and neuronal degeneration. Notably, pronounced swim bladder swelling with distinct hemorrhagic spots was observed. Antibiotic susceptibility testing showed that ZH2208 was sensitive to enrofloxacin and doxycycline but resistant to several common aquaculture antibiotics, highlighting its multidrug-resistant profile. In conclusion, this study provides the first comprehensive characterization of S. agalactiae infection in hybrid marbled goby. These findings support the development of effective prevention and control strategies, including vaccination and rational antibiotic use, to manage streptococcal disease in goby aquaculture.

Achieving systemic nonviral delivery of large nucleic acids such as mRNA to the brain is challenging due to high off-target delivery and the blood-brain barrier (BBB), a cellular barrier which prevents most nucleic acids in circulation from entering the brain. Ionizable lipid nanoparticles (LNPs) are a promising class of nanocarriers to facilitate the delivery of mRNA, as their highly modular nature enables fine-tuning of the LNP formulation for targeted delivery applications. In this work, we explore the role of ionizable lipid chemical structure and lipid molar ratios within the LNP formulation on mRNA delivery to and transfection of the brain. We utilize a high-throughput in vivo screening approach based on mRNA barcoding to study a large library of LNPs made with systematically varied ionizable lipid structures, amounts of ionizable lipid, and amounts of lipid-polyethylene glycol (PEG). We find that ionizable lipids with longer tail structures and linear amine cores can facilitate mRNA delivery to the mouse brain, and ultimately identify a specific ionizable lipid, C14-306, that facilitates brain transfection coupled with reduced liver transfection compared to an FDA-approved benchmark formulation. Furthermore, the lead LNP formulated with C14-306 is able to increase neuronal transfection and facilitate Cre-mediated recombination in the brain. Finally, safety analyses demonstrate that the lead LNP does not induce BBB leakage, increases in serum inflammatory cytokine levels, or increases in serum liver enzyme levels. Overall, our work highlights the utility of molecular barcoding for high-throughput screening of LNPs for delivery to the brain and suggests several design principles to guide the engineering of next-generation brain-tropic LNPs.

Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a systemic disorder associated with heightened risk of cognitive impairment, including mild cognitive impairment (MCI) and dementia. Epidemiological studies indicate COPD patients face a 1.74-fold higher risk of cognitive decline, with deficits predominantly affecting attention, memory, and executive functions, impairing daily living and increasing mortality risk. This review synthesizes factors linking COPD to cognitive impairment, including systemic inflammation (via proinflammatory cytokines and blood-brain barrier disruption), hypoxemia/hypercapnia (inducing oxidative stress and neuronal damage), acute exacerbations (exacerbating inflammation and persisting deficits), and comorbidities like obstructive sleep apnoea (OSA), cerebral microbleeds, and depression. Smoking’s role remains paradoxical, with neurotoxicants potentially counteracted by nicotine’s neuroprotective effects. Assessment relies on neuropsychological tools (e.g., MoCA, MMSE), neurophysiological measures (P300 ERP), and neuroimaging, though limitations persist. Interventions focus on non-pharmacological strategies: pulmonary rehabilitation (improving cognition via enhanced cerebral perfusion), cognitive training (targeting memory/attention), and long-term oxygen therapy (LTOT, reducing decline in hypoxemic patients). Critical gaps include unclear mechanisms and the need for personalized interventions. Addressing these may improve clinical outcomes and quality of life in COPD patients.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition shaped by both genetic and environmental factors. While genetic studies have identified monogenic and polygenic contributions to ASD, growing evidence suggests that environmental exposures can modulate genetic susceptibility. Among these, bisphenol A (BPA), a widely studied endocrine-disrupting chemical, has drawn attention due to its ability to cross the blood-brain barrier and placenta. BPA can influence neurodevelopment through epigenetic modifications, mitochondrial dysfunction, and oxidative stress. Elevated BPA levels have been detected in serum and urine of individuals with ASD, correlating with altered gene expression in brain regions critical for cognition and behavior. Experimental models indicate that BPA exposure disrupts neuronal viability, synaptic connectivity, and neurotransmitter regulation, potentially exacerbating ASD-like phenotypes in genetically predisposed individuals. This review explores the interaction between genetic risk factors and environmental toxins, particularly BPA, in ASD pathogenesis. By integrating findings from epidemiological studies, molecular analyses, and animal models, we highlight the need for further research into gene-environment interactions to refine ASD risk assessment and therapeutic strategies.

A series of substituted indole derivatives have been synthesized and evaluated for their atypical antipsychotic activity Compared to traditional neuroleptics, second-generation or "atypical" antipsychotics offer a more favorable therapeutic profile against both positive and negative symptoms of schizophrenia. The compounds were designed based on their physicochemical similarity studies to standard drugs and in silico (docking studies) with 5-HT2A and D2 receptors. The prepared compounds were evaluated for atypical antipsychotic activity in animal models of dopaminergic (apomorphine-induced mesh climbing behavior and stereotypy) and serotonergic antagonism (1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI) induced head twitch assay). All the test compounds showed. The potential of these compounds to penetrate the blood-brain barrier (log BB) was computed through an online software program, and the values obtained for the compounds suggest good potential for brain permeation. In-silico (docking studies) suggested good binding of the test compounds to the 5-HT2A and D2 receptors and a hypothetical binding model for the target compounds was postulated. The prepared test compounds, designated as 8 to 15, exhibited an atypical antipsychotic profile in the pharmacological assays with a mechanistic profile of combined 5-HT2A and D2 antagonism. The study has afforded novel indole-based lead molecules with potential atypical antipsychotic effect.

L17E cell-penetrating peptide enhances intranasal delivery of IgG to the cerebrospinal fluid in mice.