Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammatory demyelination in the central nervous system, predominantly presenting in young adults, with a steadily increasing global incidence. In China, MS is classified as a rare disease and imposes a considerable medical and socioeconomic burden. Current clinical management mainly relies on immunomodulatory and immunosuppressive therapies; however, limitations in long-term efficacy, safety, and economic cost highlight the need for a more comprehensive understanding of disease mechanisms. Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for investigating the immunopathological basis of MS. Although EAE does not fully replicate the heterogeneity and long-term progression of human MS, it provides an important experimental framework for elucidating specific molecular and cellular pathways involved in disease development. This review synthesizes mechanistic evidence derived from EAE studies, focusing on immune regulation, autophagy modulation, gut microbiota-brain axis interactions, maintenance of blood-brain barrier integrity, and inhibition of NLRP3 inflammasome-mediated pyroptosis. By integrating findings within these defined pathological domains, this work aims to clarify how modulation of these interconnected pathways contributes to the present understanding of MS pathogenesis and to discuss their potential clinical relevance. These findings not only enhance our understanding of MS pathogenesis but also provide a foundation for developing multi-target, synergistic therapeutic strategies.
Serum cystatin C levels are independently correlated with cognitive impairment in individuals with cerebral small vessel disease
Background and purposePrevious studies have shown that serum cystatin C (CysC) is associated with cerebral small vessel disease (CSVD) and that elevated CysC levels are linked to an increased risk of cognitive impairment in the elderly. However, whether CysC is specifically associated with cognitive impairment in patients with CSVD remains unclear.MethodA total of 334 CSVD patients with available demographic, blood biomarker, and brain imaging data were included. Patients were divided into vascular cognitive impairment and normal cognition groups. Univariate analysis was used to compare baseline data, blood biomarkers, imaging features, and behavioral scores between the two groups. Binary logistic regression was used to evaluate the diagnostic value of cystatin C for CSVD-related cognitive impairment.ResultsCompared with the normal cognition group, the VCI group exhibited significantly elevated serum levels of CysC, homocysteine, urea nitrogen, creatinine, uric acid, fibrinogen, and D-dimer, along with a lower red blood cell count. The VCI group also showed a higher prevalence of severe periventricular white matter hyperintensity, severe deep white matter hyperintensity, severe total white matter hyperintensity, and brain atrophy. The combination of these eight blood biomarkers markedly improved the diagnostic performance for VCI (AUC = 0.672, 95% CI: 0.615–0.730, p < 0.001). Multivariate analysis revealed that elevated CysC levels (OR = 2.677, p = 0.041), age (OR = 1.067, p < 0.001), and severe total WMH (OR = 2.713, p < 0.001) were associated with CSVD-related cognitive impairment. After adjusting for confounding variables, serum CysC levels remained independently correlated with cognitive impairment (OR = 3.257, 95% CI: 1.192–8.899, p = 0.021).ConclusionSerum CysC levels are independently associated with cognitive impairment in CSVD patients.
Effects of bifrontal-transcranial direct current stimulation combined with music listening on sleep quality, cortical activation and functional connectivity in patients with insomnia: a randomised controlled trial by fNIRS
BackgroundAlthough music listening and transcranial direct current stimulation (tDCS) alone have certain effects in the treatment of insomnia, the sleep regulatory effects and neural mechanisms of the combined treatment in patients with insomnia disorder (ID) are unclear. This study aimed to investigate the efficacy of combined bifrontal-tDCS (F3: anode, F4: cathode) with music listening in patients with ID using functional near-infrared spectroscopy (fNIRS).Methods76 ID patients were randomly divided into an intervention group (n=38) and a control group (n=38), and received 4 weeks of a total of 20 sessions of music + tDCS therapy and music + sham tDCS therapy (30-second stimulation with fade-in/fade-out to mimic somatic sensations), respectively. The Pittsburgh Sleep Quality Index Scale (PSQI), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and Perceived Stress Scale (PSS-14) were compared between the two groups before and after treatment. Oxy-haemoglobin (HbO2) concentration and functional connectivity (FC) were assessed during the verbal fluency task using fNIRS.ResultsCompared with the control group, the PSQI total score (mean difference: -2.57 points, 95% CI: -4.43 to -0.71, p = 0.001), PSQI sub-scores except “sleep disturbance and daytime dysfunction”, SDS and SAS scores of the intervention group improved significantly after treatment. It was observed by fNIRS that the HbO2 concentration in the medial prefrontal cortex (mPFC), left dorsolateral prefrontal cortex (DLPFC), right ventrolateral prefrontal cortex, and right superior frontal cortex (SFC) increased significantly after treatment in the intervention group but was not superior to the control group. In addition, the FC enhancement of left SFC-left DLPFC and left SFC-mPFC after treatment was significantly better in the intervention group than in the control group, and the PSQI improvement was positively correlated with the FC enhancement of channel-averaged and left SFC-right DLPFC.ConclusionsCombining bifrontal-tDCS with music listening is more helpful in improving sleep quality and prefrontal functional connectivity in ID patients compared with music listening alone. For ID patients, music electrical stimulation headphones may be a safe, effective, and convenient new treatment strategy.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2400086233.
The long-term psychological processing of an autism spectrum disorder diagnosis in parents
IntroductionA child’s ASD diagnosis represents a critical event for parents, often requiring them to face the loss of their child’s ideal image and reevaluate the family life projects. The aim of this study is to explore how parents retrospectively reconstruct and integrate their child’s ASD diagnosis through autobiographical memories.Methods21 parents, 16 mothers and 5 fathers, that received the ASD diagnosis within five years, were administered the Reaction to Diagnosis Interview (RDI). Interviews were audio-recorded, transcribed verbatim and analyzed using a two levels approach. The first one to explore the patterns of meanings that emerged in the whole parents’ autobiographical memories through the Reflexive Thematic Analysis. The second one is to identify patterns of resolution or non-resolution of the impact of the diagnosis.ResultsFindings show suffering and struggling as main themes and subthemes and a prevalence of unresolved diagnoses; gender differences in the way of managing the child-related care tasks, efforts, and coping strategies emerged.DiscussionIn line with literature, our findings suggest that the availability of supportive resources plays a crucial role in facilitating parents’ adjustment and integration of the ASD experience and harmonizing gender differences. They also emphasize that the impact of ASD diagnosis is not a single event but an ongoing process of meaning-making which changes with the child’s developmental path. Our findings highlight the need for cognitive and emotional reconstruction and reframing of parents’ autobiographical memories. These processes play a kay role in shaping how the diagnosis experience is integrated into one’s narrative identity, creating opportunities for transforming the meaning of the remembered experience.
Acupoint temperature as a biomarker: infrared thermography in the diagnosis of adolescents with major depressive disorder
BackgroundThe prevalence of adolescent major depressive disorder (MDD) is rising; however, diagnosis relies on subjective measures due to a lack of objective biomarkers. This study explored infrared thermography (IRT) as a non-invasive tool to quantify thermal radiation characteristics of acupoints in adolescents with MDD. The objective was to establish diagnostic models based on acupoint temperature-derived biomarkers.MethodsA prospective, multi-center observational study enrolled 108 participants (65 adolescents with MDD and 43 healthy controls [HCs]). We first examined correlations between acupoint temperatures and depression severity using Pearson analysis. Multiple linear and binary logistic regression models were developed to diagnose MDD and assess severity. The diagnostic model for MDD was visualized as a nomogram and validated using Receiver Operating Characteristic (ROC) curves, Hosmer-Lemeshow tests, calibration plots, and decision curve analysis (DCA). Internal validation was performed using the bootstrap method.ResultsAmong 27 acupoints analyzed, adolescents with MDD exhibited altered acupoint temperatures at Taiyang (EX-HN5), Quchi (LI11), Yanggu (SI5), and Waiqiu (GB36). Subsequent Pearson correlation analysis revealed negative correlations between the infrared relative temperatures of Taiyang (EX-HN5), Quchi (LI11), and Waiqiu (GB36) and depression severity (P = 0.001, r = -0.319; P = 0.022, r = -0.229; P = 0.001, r = -0.325) and a weak positive correlation between the infrared relative temperature of Yanggu (SI5) and depression severity (P = 0.043, r = 0.202). Building on these findings, two diagnostic models were developed: a linear regression model for depression severity of adolescents (Y = 52.25-9.52*TEX-HN5-13.07*TGB36) and a logistic regression model for adolescents with MDD diagnosis (P = ex/(1+ex), x = 0.22-1.14*TEX-HN5+0.45*TSI5-2.19*TGB36). The nomogram-based model demonstrated good calibration (Hosmer-Lemeshow P = 0.855), discrimination (AUC = 0.785, 95%CI: 0.693 – 0.876), and clinical utility. Internal validation using the bootstrap method produced a C-index of 0.752 (95% CI: 0.617 – 0.877), further confirming the model’s robustness.ConclusionsIn conclusion, acupoint temperature-based models show promising efficacy for the objective and non-invasive diagnosis and severity quantification of adolescents with MDD, offering valuable tools for early clinical intervention. Future studies should validate these findings across diverse populations and integrate multi-modal biomarkers to enhance diagnostic precision.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT06750640.
Stigma in adults with ADHD: a systematic review of types, experiences, and potential implications for quality of life
BackgroundAttention deficit hyperactivity disorder (ADHD) is a disorder characterized by hyperactive, impulsive, and/or inattentive symptoms. Adults with ADHD often report reduced quality of life (QoL) across social, educational, and occupational functioning. Part of these deficits may be attributed to stigma, which includes stereotypes, prejudices, discrimination, and negative labelling. While stigma’s effects on QoL have been extensively documented in other mental health conditions, the specific types and impacts of stigma experienced by adults with ADHD remain underexplored in recent reviews.AimsTo identify and describe the different types of stigmas experienced by adults with ADHD, while exploring how stigma may impact QoL’s key domains as defined by WHO (physical domain, psychological domain, level of independence, social relationships, environment, and spirituality/religion/personal beliefs).MethodsA literature search was conducted across APA PsycArticles, Embase, and Ovid MEDLINE(R) for ADHD AND stigma-related keywords. Eligible studies were English, peer-reviewed articles from the past decade involving adults (≥18) and describing or specifying at least one type of stigma.ResultsA total of 17 papers met the inclusion criteria. Stigma types included self-stigma and/or internalized stigma, perceived stigma, public stigma, and structural stigma. QoL domains affected included the psychological domain, social relationships, environment, and level of independence. Greater ADHD symptomatology was positively correlated with more internalized stigma, which in turn was linked to functional impairment, worse self-esteem, and poorer QoL. Self-stigma manifested as self-deprecating labels and ADHD devaluation. Perceived stigma hindered treatment seeking, medication compliance, and diagnostic disclosure, although associations with QoL were insignificant. Public stigma was the most investigated and related to negative societal attitudes, notably in academic contexts. Few studies looked at structural stigma; those that did identified structural barriers to care, though none directly assessed QoL outcomes.ConclusionStigma remains pervasive, though direct effects on QoL domains are less widely investigated. Future studies should investigate structural stigma in more depth and explore causal relationships between stigma and QoL.Systematic Review Registrationhttps://doi.org/10.17605/OSF.IO/Y52HK
PAD-S/CSA as a candidate shared representation layer for computational psychotherapy: minimal architecture and a staged validation roadmap
Psychotherapy schools often describe overlapping process phenomena in non-interoperable vocabularies. This pluralism is clinically valuable but computationally costly: datasets become difficult to compare, clinically load-bearing distinctions are collapsed into convenience labels, and artificial intelligence (AI) systems inherit annotation schemes rather than a clinically interpretable intermediate representation. Building on the Perceive–Assess–Dose–Safeguard (PAD-S) framework and the Conflict-Square Algorithm (CSA), this theory article asks a narrower question than the prior PAD-S and CSA papers: can the same variables be formulated as a candidate shared representation layer between heterogeneous observation models and school-specific intervention policies? The proposed layer projects a high-dimensional biopsychosocial state into four clinically observable process coordinates—defensive/avoidant organization (DEF), anxiety/arousal and tolerance (ANX), progression toward direct experience and action (PRO), and self-attack/shame processes (SUP)—plus a safety threshold that constrains admissible intervention intensity. The contribution is architectural rather than empirical: it isolates the representational role from earlier decision-grammar and transcript-coding roles; clarifies the distinction between observations, representation, and policy; specifies a minimal falsifiable family of state-transition models; illustrates translation across four pragmatic therapy families; and defines a staged validation order from reliability and function linkage to transcript-level predictive operationalization and only then sparse equation discovery. The framework should therefore be read as a candidate shared representation layer for computational psychotherapy and computational psychiatry rather than as a therapy protocol, a fitted predictive model, a complete generative theory, or an autonomous decision system. No new dataset, fitted classifier, transcript-level predictive result, or discovered equation is reported here. The article aims instead to state what would count for or against PAD-S/CSA as a clinically interpretable interface for later empirical modeling.
Tuning the immune response to mRNA vaccines
Nature Biotechnology, Published online: 29 April 2026; doi:10.1038/s41587-026-03125-0
A strategy to control translation of mRNA vaccines reveals cell type–specific contributions to immunity that may be harnessed to enhance vaccine efficacy.
mRNA vaccine immunity is enhanced by hepatocyte detargeting and not dependent on dendritic cell expression
Nature Biotechnology, Published online: 29 April 2026; doi:10.1038/s41587-026-03099-z
mRNA vaccine efficacy is enhanced by silencing cell-type-specific expression.
Predicting referral need for febrile children in low-resource community settings in South and Southeast Asia
Nature Medicine, Published online: 29 April 2026; doi:10.1038/s41591-026-04338-1
A multicountry cohort study found that prediction models combining clinical parameters with either pulse oximetry or the host biomarker sTREM1 more accurately identified febrile children needing referral than standard WHO criteria.