Journal of Advanced Research

The most prevalent RNA alteration in the mammalian genome is N-6-methylenediosine (m6A). There is mounting evidence linking dysregulation of m6A regulatory factors and alterations in m6A levels to the development, course, or prognosis of ovarian cancer. Genes having prognostic value were screened using the univariate, multifactorial, and Least Absolute Shrinkage Selection Operator (LASSO) Cox regression analyses. Important genes' m6A expression in clinical material was verified by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). In present study, all 23 regulators were significantly differentially expressed in ovarian cancer tissues. LASSO regression analysis screened for 10 key genes associ-ated with both autophagy and m6A. A risk score was constructed and nomogram was developed to forecast the prognosis of ovarian cancer patients. Additionally, individuals with ovarian cancer were classified as high-risk or low-risk; and the low-risk group might be more likely to benefit from im-munotherapy. RT-qPCR was used for the bioinformatics study of human ovarian cancer and normal tissues. Lastly, PLK2 and LEPR were confirmed to be associated with tumorigenesis in scRNA-seq. The risk score established by m6A and autophagy can be used to predict prognosis and susceptibility to anticancer drugs in patients with ovarian cancer.

Neuropsychiatric symptoms are considered the most common feature of long COVID disease. Recent studies have demonstrated structural brain changes and highlighted the importance of neuroinflammation in the development of cognitive deficits as seen in long COVID patients. In addition, peripheral studies have demonstrated heterogeneous molecular subtypes of long COVID pathology. However, it is unknown which peripheral metabolomic alterations occur in patients with neuropsychiatric long COVID syndrome and how these relate to symptom severity. In the present study, we investigated differences in the peripheral serum metabolome profiles of healthy controls and patients with long COVID syndrome with neuropsychiatric symptoms. We found that patients with long COVID showed peripheral alterations in lipid species such as triacylglycerides and acylcarnitines. Furthermore, metabolites altered in patients with long COVID syndrome were also associated with depressive and fatigue symptom burden as well as with differences in cortical thickness in multiple brain regions. Our results demonstrate a metabolic phenotype of long COVID patients that may reflect a dysregulation of lipid metabolism and deficits in mitochondrial energy production as potential contributors to symptom burden and brain structural alterations. These data may serve as a resource and basis for further studies aimed at investigating peripheral molecular alterations in patients with neuropsychiatric long COVID syndrome.

BackgroundMetabolic reprogramming is a common occurrence in tumor cells, where enhanced glycolysis promotes cell growth, invasion and migration. NF1 is tumor suppressor gene that downregulates the encoded neurofibromin protein. However, the effects of NF1 on energy metabolism and epithelial-mesenchymal transition (EMT) in glioblastoma multiforme (GBM), as well as the underlying molecular mechanisms, remain unclear. MethodsCRISPR/Cas9 gene editing technology was employed to construct GBM cell lines with NF1 gene mutations. Metabolomics was utilized to examine the impact of NF1 on metabolic remodeling in GBM. The Seahorse XF24 extracellular flux analyzer was used to detect the effect of NF1 knockdown on glycolysis and mitochondrial oxidative phosphorylation in GBM cells. Wound healing assay and Transwell chamber assay were utilized to detect the effect of NF1 on GBM cell invasion. Orthotopic tumor model in nude mice was established to explore the role of NF1 in vivo. In addition, Co-IP, western blotting, and immunofluorescence were used to explore the changes of key enzymes in glycolysis and mitochondrial oxidative phosphorylation and the relationship between NF1 and MFN1. ResultsThe expression of NF1 is decreased in glioma tissues and is significantly correlated with patient prognosis. NF1 knockdown may promote the invasion, migration, and EMT of GBM cells. At the same time, the activation of the AKT/mTOR signaling pathway promotes aerobic glycolysis in GBM cells, promotes mitochondrial division through targeted regulation of MFN1, and inhibits mitochondrial oxidative phosphorylation. NF1 deficiency promotes EMT in GBM cells by enhancing aerobic glycolysis and mitochondrial division. ConclusionNF1 deficiency promotes GBM glycolysis by activating the AKT/mTOR signaling pathway and inhibits the mitochondrial oxidative phosphorylation by regulating MFN1; NF1 deletion promotes GBM EMT by remodeling the pattern of energy metabolism.

Melittin, a potent amphipathic cationic peptide derived from bee venom, exhibits broad-spectrum antineoplastic efficacy, notably against cervical carcinoma. Despite its established therapeutic potential, the global transcriptional reprogramming orchestrating its acute multi-pathway cytotoxicity remains incompletely understood. To bridge this knowledge gap, we generated the first comprehensive, untargeted RNA-seq dataset profiling the acute phase of melittin-induced cell death in murine cervical carcinoma U14 cells (exposed to 4 g/mL melittin for 20 minutes) alongside untreated controls. Utilizing deep sequencing and rigorous bioinformatics workflows, we quantified genome-wide mRNA abundances and mapped a distinct transcriptomic shift, identifying 254 significantly differentially expressed genes, comprising 158 up- and 96 down-regulated transcripts. Validated by stringent quality control metrics, exceptional genomic mapping rates, and comprehensive functional annotations via the GO and KEGG databases, this high-resolution transcriptomic resource provides a systems-level map of early molecular alterations. All raw and processed sequencing data are publicly available. This transcriptomic resource provides a valuable foundation for elucidating the acute regulatory networks underlying melittin-induced anti-cervical cancer effects. DatasetThe dataset can be accessed through the NGDC website by searching with the BioProject accession number PRJCA068439. Reviewers may use this link for anonymous access during the review process. Direct URL to data: Genome Sequence Archive-CNCB-NGDC

Nasal fluid collected at the brain-nose interface (BNI) may provide a minimally invasive window into central nervous system (CNS) biology, but its suitability for deep, reproducible proteomics remains unclear. Here, we establish and benchmark a standardized liquid chromatography-tandem mass spectrometry workflow for BNI proximal nasal fluid and compare its proteome to matched cerebrospinal fluid (CSF) from 40 individuals with cognitive impairment. Using pooled nasal fluid, we identified single pot, solid phase sample preparation combined with data independent acquisition (DIA) as the optimal strategy, with low coefficients of variation. In cognitively impaired cohort, DIA based proteomics on a timsTOF pro quantified on average 5,210 proteins in nasal fluid and 1,800 in CSF, with 4,901 nasal fluid proteins detected in at least 75% of samples. Nasal fluid contained nearly 50% of the CSF proteome (876 shared proteins), including numerous CNS and neurodegeneration associated species. The result of this exploratory study position BNI derived nasal fluid as a robust, proteome rich biofluid for proteomics driven CNS biomarker research.

Preeclampsia (PE) is a severe pregnancy-associated hypertensive disorder and a major contributor to maternal and perinatal morbidity and mortality. The mechanisms of PE pathogenesis are not yet understood. This paper aims to explore candidate PE-associated biomarkers and regulatory mechanisms using bioinformatics analysis of placental transcriptomic datasets. We downloaded placental transcriptomic datasetsGSE203507 and GSE148241 from GEO and investigated differentially expressed genes(DEGs) between PE and control samples. We performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO), and protein-protein interaction (PPI) analyses to characterize the potential role, disease associations, and interaction networks of the DEGs. We validated the mRNA expression patterns of candidate hub genes using two independent placental transcriptomic datasets, GSE143966 and GSE114691.We identified 263 DEGs in the discovery analysis and further obtained 150 overlapping DEGs including80 upregulated genes and 70 downregulated genes, for downstream analysis. We then identified eight candidate hub genes: OPRK1, OXGR1, HCAR3, CCR5, HCAR2, CXCL1, FPR3, and SSTR1using Meta scape software(v3.5.20260201). In the validation phase, most candidate hub genes showed broadly consistent mRNA expression trends across GSE114691 and GSE143966, while FPR3 showed weaker cross-dataset consistency. These findings provide candidate PE-associated genes and regulatory pathways for further experimental and clinical validation..

Background: Major depressive disorder (MDD) is a severe mental illness associated with severe clinical consequences and substantial societal burden. It's characterized by immune-inflammatory dysregulation and immune sensitization. Objective: To determine whether in vitro ketamine attenuates phytohemagglutinin (PHA)/lipopolysaccharide (LPS)-induced immune sensitization in patients with MDD and healthy controls (HCs). Methods: Whole blood from 18 patients with MDD and 18 HCs was stimulated with PHA/LPS and exposed to ketamine (0.3 M, 0.6 M, and 6 M) for 72 hours. Cytokines, chemokines, growth factors, and composite immune profiles, including M1/M2 macrophages, T helper (Th)1/2/17, the immune-inflammatory response system (IRS), and compensatory immunoregulatory system (CIRS), were synthesized and determined. Results: Under PHA and LPS stimulation in vitro, the MDD group exhibited markedly elevated immune profiles, including M1, M2, Th1, Th2, Th17, IRS, CIRS, chemokines, and growth factors, consistent with immune sensitization. Significant group-by-treatment interactions were observed for Th1-Th2, M2, growth factors, IL-12(p70), M1, and chemokines. Ketamine produced minimal changes in HCs but broader suppression in MDD, particularly at the highest concentration, without normalizing the sensitized immune phenotype. Among the immune markers with no notable group-by-treatment interactions, ketamine exerted diagnosis-independent effects, decreasing MIP-1{beta}, IL-1&{beta}, Th1, TNF-{beta} IRS, IFN-{gamma}, and IL-2 compared to the control condition. Conclusions: Ketamine exhibited two distinct immunoregulatory patterns: selective, disease-dependent attenuation of sensitized immune pathways and broader, diagnosis-independent suppression of the stimulated immune response, predominantly at higher concentrations. However, these effects were insufficient to normalize the immune-sensitized phenotype of MDD.

Background: Detecting higher order relationships in datasets of complex traits, such as multiple sclerosis (MS), has been challenging. Conventional statistics largely rely on comparing averages across groups and thereby discard important information on the underlying distribution of datapoints. The Genomic Information Field Theory (GIFT) overcomes this limitation by ranking individuals based on linear measures, for example immunoglobulin titres. The exact role of humoral immune responses against several human herpes viruses in a sex-dependent manner in MS is currently unknown. Materials and methods: We compared the performance of GIFT with conventional statistical frameworks to detect differences in the humoral immune response against 4 highly prevalent herpes viruses linked to an individuals susceptibility to develop MS in 200 MS patients and 137 healthy controls. Results: GIFT validated the well-known association that the Epstein Barr Virus (EBV) protein EBNA1 is strongly linked to MS susceptibility in both sexes. In contrast to conventional statistics, GIFT also identified association between herpes simplex virus, varicella zoster virus and the EBV VCA protein and female susceptibility to develop MS, whereas male MS susceptibility was only linked to CMV immunoglobulin levels. None of these associations was observed using conventional statistical tools. Conclusion and discussion: We here show for the first time that GIFT is able to detect novel associations in human immunoglobulin data linked to MS susceptibility, which remained undetected by conventional statistical frameworks. This shows the power of GIFT to detect complex phenotype-trait associations and underlying subgroups within populations.

Objective: To identify the latent profiles of stigma among breast cancer patients following modified radical mastectomy and to analyze their influencing factors, thereby providing an empirical foundation for tailored psychological nursing interventions.Methods: A convenience sampling strategy was employed to recruit 276 post-mastectomy breast cancer patients from the breast surgery department of a tertiary care hospital in Sichuan Province between January 2026 and May 2026. Data were collected using a general demographic questionnaire, the Social Impact Scale (SIS), the Self-Compassion Scale (SCS), and the Multidimensional Scale of Perceived Social Support (PSSS). Item scores of the SIS served as explicit indicators for latent profile analysis (LPA). Univariate analysis and multinomial logistic regression were conducted to identify independent predictors associated with stigma profile membership.Results: The total SIS score among post-mastectomy breast cancer patients was 53.88{+/-}7.90, indicating a moderate level of stigma. LPA yielded three distinct latent profiles: the low-stigma profile (22.1%), moderate-stigma profile (57.2%), and high-stigma profile (20.7%). Multinomial logistic regression analysis demonstrated that age, educational level, employment status, monthly per capita income, affected upper-limb paresthesia, clinical TNM stage, self-compassion, and perceived social support were independent predictors of stigma profile membership (all P<0.05).Conclusion: Stigma among post-mastectomy breast cancer patients exhibits substantial latent heterogeneity, categorizable into three distinct psychological profiles. Healthcare professionals should pay particular attention to patients who are younger, more highly educated, face heavier economic burdens, present with affected upper-limb paresthesia, or are diagnosed with advanced TNM stages. Implementing stratified and individual-tailored interventions focused on cultivating self-compassion and bolstering social support is essential to attenuate stigma and foster postoperative psychological recovery.

Endophytic fungi associated with the Himalayan yew (Taxus wallichiana) represent an underexplored source of bioactive secondary metabolites. This study investigated the extracellular metabolites of Annulohypoxylon purpureonitens isolated from Nepalese T. wallichiana using bioactivity screening combined with LCMS/MS-based metabolomics. The fungal extract exhibited broad-spectrum antibacterial activity, showing the strongest inhibition against Staphylococcus aureusand Enterococcus faecalis (MIC = 500 ug/mL). It also displayed notable antioxidant capacity(DPPH, ABTS, TPC &TFC) and cytotoxicity against HeLa and MCF-7 cancer cell lines. Metabolite profiling via GNPS molecular networking, manual MS/MS validation, and MASST reverse metabolomics putatively identified diverse compounds, including hydroquinidine, chlorogenic acid, muramic acid, and cordycepin conjugates widely distributed across public microbial datasets. Overall, A. purpureonitens is a promising source of multifunctional metabolites, laying a foundation for future compound isolation and functional characterization.

A protein whose removal or deletion causes significant disruption or collapse of a protein-protein interaction (PPI) network is referred to as a vulnerable protein. Such proteins may serve as valuable therapeutic or diagnostic targets in disease-associated networks. In this study, two PPI networks were constructed, one for HPV-positive and the other for HPV-negative head and neck squamous cell carcinoma (HNSCC), and the vulnerable proteins of these networks were identified by the node deletion approach. After analyzing the networks, 27 unique vulnerable proteins in HPV-positive and 72 unique vulnerable proteins in HPV-negative HNSCC were identified. Among them, one HPV-positive and seven HPV-negative HNSCC vulnerable proteins were further chosen by integrating multi-omics data. To exploit the vulnerabilities of these proteins, candidate synthetic lethal (SL) partners were predicted whose inhibition may selectively impair tumor survival. Subsequently, drug-gene interaction analysis was performed to identify inhibitors targeting the SL partners of these vulnerable proteins. Notably, in HPV-positive HNSCC, TOP2A, CHEK1, and CHEK2 genes were identified as SL partners of TTN, and their inhibitors were already clinically approved. While in HPV-negative HNSCC, ADA and MMP19 were identified as an SL partner of LMO7; TMEM45B, CDH3, and ELF3 genes were identified as an SL partner of CGN; and ZNF433 was identified as an SL partner of FLNC. However, MMP19, ZNF433, and TMEM45B inhibitors were not reported. Thus, these vulnerable proteins, including their SL partners, provide novel avenues to explore and develop more efficient and precise therapeutic and diagnostic strategies.

Introduction: Congenital cytomegalovirus (cCMV) is the most common congenital viral infection and a leading non-genetic cause of neurodevelopmental impairment. Current diagnostic methods using fetal biofluids provide limited insight into fetal pathophysiology. Extracellular vesicles (EVs) in amniotic fluid (AF) are a promising source of stable biomolecules that reflect real-time fetal physiology. This proof-of-concept study compared amniotic fluid EV (AF-EV) characteristics in fetuses with severe CMV infection with those of uninfected fetuses and aimed to develop hypotheses about fetal response to cCMV in utero. Methods: AF samples were collected from pregnancies with symptomatic CMV infection and gestational-age-matched uninfected controls (4 pairs, n=8 total). EVs were isolated and characterised by Western blotting, cryo-electron microscopy, and nanoparticle tracking analysis. Label-free quantitative proteomics identified CMV-associated changes in the AF-EV proteome. Results: CMV-infected AF showed higher vesicle levels (Hedges' g = 1.55), indicating inflammation and virus-induced changes in EV biogenesis. Proteomic analysis found 8.6% of proteins dysregulated. Upregulated proteins included haemoglobin subunits, immunoglobulin heavy chain mu, and myeloperoxidase (Hedges' g = 1.51 to 1.88), indicating haemolysis and immune activation. Eleven host proteins related to neurodevelopment, mitochondrial function, lipid metabolism, and Golgi trafficking were absent in infected cases, indicating viral disruption of host pathways. Protein enrichment analysis revealed differences in neurological, haematological, and immune pathways, aligning with severe cCMV pathology. Conclusion: This study acts as a proof-of-principle investigation of the AF-EV proteome in cCMV. Although the results highlight key protein signatures associated with severe fetal outcomes, they primarily serve to generate hypotheses and inform larger prospective studies.

Introduction: Advanced biomaterials for regenerative medicine are increasingly expected to combine multifunctionality and compatibility with tissue-specific cellular processes. In this context, hydroxyapatite-based platforms modified through ionic substitution represent promising candidates, as they may integrate structural similarity to bone mineral with additional biological functionality and luminescent properties, enabling diagnostic applications and real-time monitoring. In this study, we evaluated whether silicate-phosphate substituted calcium hydroxyapatite Ca10(PO4)6-x(SiO4)x(OH)2 (where x = 1.5) co-doped with lithium(I), europium(III), and gadolinium(III) ions (Si-HAp-LEG) affects the osteogenic, chondrogenic, and adipogenic differentiation potential of human bone marrow stromal/stem cells (BMSCs). Methods: Human BMSCs were cultured under lineage-specific differentiation conditions in the presence of undoped silicate-substituted phosphate hydroxyapatite (abbr. as Si-HAp), which served as a control, and two distinct Si-HAp-LEG formulations differing in gadolinium(III) (Gd3+) as well as lithium (Li+) and europium(III) (Eu3+) ion concentrations: Si-HAp-LEG-221 (1 mol% Gd3+ ion) and Si-HAp-LEG-222 (2 mol% Gd3+ ion). Differentiation-associated phenotypic outcomes, including extracellular matrix formation and lipid accumulation, were evaluated using Safranin O, Alizarin Red, and Oil Red O staining. In parallel, biomaterial-induced molecular responses were characterized at the transcriptomic and protein levels using RT-qPCR for selected coding and non-coding RNAs and Western blot analysis for representative lineage-associated proteins. Results: Histochemical evaluation confirmed that, across all tested biomaterial groups, BMSCs retained the ability to form mineralized calcium deposits, proteoglycan-rich extracellular matrix, and intracellular lipid accumulation under osteogenic, chondrogenic, and adipogenic conditions, respectively. Quantitative staining analysis revealed no significant Si-HAp-LEG-dependent enhancement of terminal differentiation outcomes compared with undoped Si-HAp. In turn, the molecular response differed between biomaterials modifications. Si-HAp-LEG-222 induced the most prominent changes in transcriptional and post-transcriptional regulators, particularly within BMP/SMAD-associated pathways under osteogenic and chondrogenic conditions, underlying a potential link between gadolinium concentration and osteogenic lineage commitment. However, these transcriptomic responses were not mirrored by consistent changes at the protein level. The results suggest that silicate-phosphate substituted hydroxyapatite co-doped with Li+, Eu3+, and Gd3+ ions primarily affects the early regulatory pathways associated with BMSCs differentiation rather than enhancing their terminal maturation. Discussion: In conclusion, the collective data indicate that Li+, Eu3+, and Gd3+ ions LEG co-doping broadens the multifunctional potential of Si-HAp by introducing imaging-related properties while preserving its underlying pro-regenerative character. Li+, Eu3+, and Gd3+ ions co-doped LEG-substituted Si-HAp may therefore be considered a compatible biomaterial platform that maintains BMSC cellular plasticity and supports balanced, differentiation-dependent modulation of lineage-associated molecular responses.

The intrauterine environment has traditionally been viewed as a privileged site protected by the placental barrier. However, emerging evidence suggests that early in utero microbial exposure may prime the developing fetal immune system. Here, using target-enriched metagenomics and high-dimensional proteomics, we characterized the intra-amniotic viral landscape and immune networks in 114 healthy pregnancies including both normal and anomalous fetuses. We identify a sparse yet heterogeneous human viral signature in 26% of samples, predominantly composed of Herpesviridae, Polyomaviridae, and Picornaviridae. Although viral reads abundance was associated with fetal abnormalities, viral detection generally did not induce overt inflammatory activation, supporting a state of immune homeostasis within the amniotic cavity. Instead, viral presence was associated with subtle and selective immune modulation, including altered inducible antimicrobial peptide expression (HBD-2 and HBD-3), coupled with an attenuation of regulatory cytokines. Our results further reveal that the amniotic immune environment is primarily governed by gestational age, transitioning from a Th1-predominant "alert" phase to innate-readiness preceding parturition. These findings suggest that fragments of viral genetic material within the amniotic cavity may contribute to fetal immune instruction without triggering overt inflammation, providing a foundational framework for understanding how "silent" viral-exposure during gestation influences the developmental origins of neonatal immunity.

Vocal fold (VF) fibrosis is a major cause of persistent dysphonia due to excessive extracellular matrix deposition and tissue stiffening that disrupt normal vocal fold vibration. Current treatment approaches are limited by the need for repeated local injections and inadequate long-term therapeutic control. Pirfenidone (PFD), an FDA-approved antifibrotic agent, has demonstrated potential for reducing fibrosis; however, its short half-life and systemic adverse effects limit conventional administration strategies. In this study, we developed a sustained and near-infrared (NIR)-responsive local delivery platform by integrating PFD-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles into biodegradable PLGA implants for dose-controllable antifibrotic delivery. PFD-loaded PLGA nanoparticles were fabricated using an oil-in-water emulsion solvent evaporation method and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Nanoparticles with small, medium, and large hydrodynamic diameters were generated to evaluate the effect of particle size on release behavior. Gold nanorods (AuNRs) were incorporated to enable photothermal NIR-triggered release enhancement. The nanoparticles were subsequently loaded into non-porous PLGA (90:10) implants and evaluated for long-term in vitro release under physiological conditions with and without pulsed 1064 nm laser irradiation. The nanoparticle-loaded implants demonstrated sustained PFD release for over 190 days with minimal initial burst release (<2.5%). NIR irradiation enhanced PFD release compared with non-irradiated controls across all nanoparticle sizes. Smaller nanoparticles produced greater cumulative release than medium and large nanoparticles due to shorter diffusion pathways and larger surface-area-to-volume ratios. Prior to implant fracture, cumulative PFD release reached approximately 20.2%, 14.8%, and 12.3% of total loading for small, medium, and large nanoparticle groups under 2-min irradiation conditions, respectively. Dialysis membrane studies further demonstrated that the PLGA capsule acted as an additional diffusion barrier that substantially prolonged release compared with nanoparticles alone. Overall, this study demonstrates a hybrid nanoparticle-in-implant strategy capable of providing sustained and irradiation-enhanced local PFD delivery with tunable release characteristics. These findings support the potential of biodegradable, dose-controllable implant systems for long-term management of vocal fold fibrosis while reducing the need for repeated interventions.

Human hair is a common contaminant in GMP-controlled manufacturing environments, and its identification is important for contamination source investigation and corrective action. Because human hair can originate from multiple body sites, it is often necessary to determine not only the species of origin but also the anatomical source of the hair. Conventional forensic approaches distinguish scalp hair from body hair by microscopic examination of cuticle patterns, medullary structure, cross-sectional morphology, and pigment distribution. However, these methods depend on examiner expertise, are difficult to apply to damaged specimens, and provide limited quantitative information. In this study, we developed a proteomics-based approach for distinguishing scalp hair from pubic hair using identical sample preparation and analytical workflows. Comparative proteomic analysis identified keratin-associated proteins KAP 4-3 and KAP 9-6 as enriched in scalp hair, whereas cuticular keratins Ha7 and Ha8 were strongly enriched in pubic hair. Amino acid composition analysis further revealed that scalp hair-enriched proteins were highly cysteine-rich, consistent with sulfur-rich cross-linking matrix proteins, whereas pubic hair-enriched proteins exhibited characteristics of structural keratin filaments. These results demonstrate that proteomic signatures can provide a quantitative and objective means of determining the anatomical origin of human hair and may contribute to contamination source tracing in GMP manufacturing and forensic investigations.

Background: Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system marked by demyelination and neurodegeneration. Beyond physical symptoms, MS is often linked to clinically relevant sleep disturbances. The variability and unpredictability of symptoms and disease progression can also fuel fear of relapse (FoR), undermining well-being and potentially increasing morbidity through inflammatory processes. Understanding biopsychosocial risk factors, including childhood maltreatment (CM) and sleep, in relation to FoR remains an important gap in MS management and research. Methods: Data from N = 48 participants were collected via an online survey. We used the Pittsburgh Sleep Quality Index (PSQI), the Fear-of-Relapse Scale (FoR), and the Childhood Trauma Questionnaire (CTQ) to assess the variables of interest. In addition, time points of exposure to different CM subtypes were assessed. Linear regression analyses were conducted to examine associations within the proposed negative triad. Results: A significant negative association between overall sleep quality and FoR was observed. In the total cohort, the interaction between CM and sleep was not a significant predictor of FoR. However, exploratory analysis revealed a significant interaction between CM and sleep among male participants, whereas the same interaction was not significant among female participants. Conclusion: A history of CM and impaired sleep quality introduce new stressors in managing one's own illness that have received little attention to date. However, the present study found that these factors were at least partly influential on the FoR. The results underscore the translational need for additional support services to enhance prevention and personalized care.

Background: Real-world evidence evaluating the long-term effectiveness and safety of dimethyl fumarate (DMF) in relapsing-remitting multiple sclerosis (RRMS) remains limited, particularly in Middle Eastern populations. Furthermore, whether previous exposure to disease-modifying therapies influences longitudinal treatment response has not been adequately characterized. We evaluated the real-world effectiveness, safety, and temporal treatment dynamics of DMF in RRMS and compared outcomes between treatment-naive and previously treated patients. Methods: This longitudinal observational cohort study enrolled 120 adults with RRMS initiating DMF (TECRA (R)) at two multiple sclerosis centers in Iran. Clinical outcomes, magnetic resonance imaging (MRI) activity, disability progression, and adverse events were assessed over 18 months at 6-month intervals. Repeated Expanded Disability Status Scale (EDSS) measurements were analyzed using linear mixed-effects models, while relapse counts and MRI lesion activity were evaluated using generalized estimating equations. Prespecified subgroup analyses examined differences according to prior treatment status. Results: Ninety-five patients completed the study. DMF produced a marked suppression of disease activity, reducing the annualized relapse rate by 95% (1.56 {+/-} 0.93 to 0.08 {+/-} 0.24; P < 0.001). EDSS improved during the first year and remained near baseline after 18 months despite a modest increase during the final follow-up interval. MRI inflammatory activity declined significantly throughout follow-up, although a mild increase in gadolinium-enhancing lesions after 12 months suggested possible attenuation of treatment effect over time. Overall, 88.4% of patients remained relapse-free, 70.5% demonstrated no MRI disease activity, and 64.2% achieved no evidence of disease activity (NEDA-3). While overall clinical outcomes were comparable between treatment-naive and previously treated patients, longitudinal analyses revealed distinct temporal patterns of MRI activity between groups. DMF was well tolerated, with predominantly mild cutaneous and gastrointestinal adverse events and infrequent treatment discontinuation. Conclusions: In conclusion, DMF was well tolerated and effective in reducing clinical and radiological disease activity. These findings support the long-term effectiveness of DMF in routine clinical practice while highlighting the importance of continued clinical and radiological monitoring to optimize individualized treatment strategies.

Introduction: Bipolar disorder (BD) has been associated with increased medical burden and accelerated biological aging. Long non-coding RNAs (lncRNAs) regulate molecular pathways related to cellular senescence, inflammation, and telomere maintenance, which are implicated in both BD and aging. This study examined whether aging-related lncRNA expression reflects familial vulnerability or illness-specific effects, and whether childhood trauma and lifestyle factors modulate these signatures within a gene-environment framework. Methods: In this cross-sectional study, expression levels of aging-related lncRNAs, including Antisense Non-coding RNA in the INK4 Locus (ANRIL), HOX Transcript Antisense Intergenic RNA (HOTAIR), Nuclear Enriched Abundant Transcript 1 (NEAT1), Taurine Upregulated Gene 1 (TUG1), Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), Growth Arrest-Specific 5 (GAS5), and Telomerase RNA Component (TERC), were measured in peripheral blood mononuclear cells (PBMCs) from individuals with bipolar disorder (BD) (n=68), siblings without BD diagnosis (SIB) (n=54), and healthy controls (HC) (n=70) using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Childhood trauma and lifestyle were assessed using the Childhood Trauma Questionnaire (CTQ) and the Healthy Lifestyle Profile II (HPLP-II). Principal component analysis generated a composite aging-related lncRNA factor. Results: At the individual transcript level, NEAT1 and TERC were elevated, whereas GAS5 was reduced, in both BD and SIB relative to HC. The aging-related lncRNA composite score was higher in BD and SIB than in HC (F = 7.315, p = 0.001). Familial liability to BD (presence vs. absence of familial liability) showed a significant main effect on the composite score (F(1,182)=8.18, p=0.005) and interacted with childhood trauma (F(1,182)=10.14, p=0.002). In multivariable models, total CTQ and physical neglect were independently associated with lower composite scores, while familial liability remained a positive predictor (all p<0.001). Conclusions: Aging-related lncRNA alterations mark familial vulnerability to BD and are shaped by childhood trauma within a gene-environment interaction framework.

Background The global prevalence of autism spectrum disorder (ASD) has significantly increased over the past two decades. Despite substantial research advances, critical aspects, including etiology, diagnostic biomarkers, and pharmacological interventions, remain incompletely elucidated. This persistent knowledge gap warrants systematic mapping of the field's evolution to inform future research priorities. Methods A bibliometric analysis of ASD-related publications indexed in Web of Science was conducted from January 2020 to May 2025. Following a systematic deduplication process, original articles, reviews, case reports, and clinical trials were included in the analysis. The analytical framework comprised co-authorship networks, institutional collaboration patterns, national research contributions, and keyword co-occurrence structures, all of which were examined using CiteSpace (version 5.8.R3) and VOSviewer. Results After deduplication, 8,162 publications (January 2020-May 2025) were analyzed. The annual output grew steadily, confirming ASD as a sustained priority in neuroscience. Research remains academia-driven, led by the United States, with China as the second-largest contributor. Chinese institutions place greater emphasis on mechanistic and developmental phenotyping, which aligns with national priorities. These studies maintain strong methodological rigor, and their growing volume underscores the central role of ASD in translational neuroscience. Conclusion Future research on ASD should focus on strengthening case identification, refining clinical phenotyping, and expanding large-scale cohort studies to advance our understanding of its etiology and identify reliable diagnostic biomarkers. It is equally important to develop and evaluate targeted interventions for core symptoms and integrate telemedicine into service delivery models. A critical yet understudied priority is improving the quality of life for autistic individuals and their families, an area in which research globally, including in China, requires greater depth and consistency. With China's growing investment in autism research, it is well-positioned to contribute to these pressing international challenges.