Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, and magnetic resonance imaging (MRI) has become an important tool for its auxiliary diagnosis because it can reveal key structural abnormalities, including hippocampal and parahippocampal atrophy, ventricular enlargement, temporal cortical degeneration, and gray matter loss. However, reliable stage-aware classification remains challenging because current methods are still limited in handling weak anatomical boundaries, low-contrast lesions, subtle inter-stage differences, and the semantic gap between neuroimaging features and clinical descriptions. To address these issues, we propose AFCG-Net, a diagnosis-guided and frequency-aware cross-modal network for joint MRI-text diagnosis. The framework consists of three stages: anatomy-guided visual encoding, cross-modal semantic alignment, and gated fusion with anatomical priors. Specifically, ASFG enhances visual representations through multi-scale modeling and low frequency-guided refinement, CASF strengthens the consistency between clinical semantics and imaging features, and AGDF performs anatomy-guided deep fusion to improve both discriminability and interpretability. Experiments on a combined cohort of 4,197 original MRI-text samples, including 2,106 self-collected samples and 2,091 ADNI samples, show that AFCG-Net achieves Precision, Recall, and F-score values of 96.3%, 96.5%, and 95.8%, respectively. The proposed method achieves the best results in the Mild dementia and Moderate dementia categories, while also showing stronger performance in the more challenging Non-dementia and Very Mild dementia categories. These results suggest that AFCG-Net provides an effective and interpretable multimodal solution for AD-assisted diagnosis.
Micro- and nanoplastics as environmental modifiers of neuroimmune dysfunction in Parkinson’s disease
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and the aggregation of α-synuclein, with increasing evidence implicating environmental factors and neuroimmune dysfunction in its pathogenesis. Micro- and nanoplastics (MNPs), ubiquitous environmental pollutants generated from plastic degradation, have recently emerged as potential biological stressors capable of entering the human body and accumulating in sensitive tissues, including the brain. Due to their small size, environmental persistence, and capacity to carry toxic additives and environmental contaminants, these particles can induce oxidative stress, impair mitochondrial and lysosomal function, and activate both innate and adaptive immune responses. This review summarizes current evidence linking microplastic exposure to neuroinflammatory processes relevant to PD, with a particular focus on microglial activation, astrocyte reactivity, peripheral immune involvement, and dysfunction of the gut–brain axis. Although a direct causal relationship between MNPs and PD has yet to be established, and direct human epidemiological evidence linking MNP exposure to PD is currently absent, the immunotoxic and neuroinflammatory effects of these particles suggest that they may contribute to disease susceptibility and progression. Elucidating the interactions between MNPs and neuroimmune pathways may help refine current frameworks linking environmental exposure, neuroimmune dysfunction, and PD susceptibility.
The relationship between intracranial artery hemodynamics and subjective cognitive decline in patients with cerebral small vessel disease: a 4D flow study
BackgroundRecent studies link disrupted intracranial artery hemodynamics, including pulsatility index (PI), resistance index (RI), and wall shear stress (WSS), to neuroimaging features of cerebral small vessel disease (CSVD). Cognitive dysfunction is a key clinical manifestation of CSVD. Subjective cognitive decline (SCD), considered a pre-mild cognitive impairment stage, enables early identification and intervention to control cognitive decline. Nevertheless, scholarly investigation on SCD in CSVD and its underlying hemodynamic mechanisms remains limited.ObjectiveThis study aims to utilize 4D flow magnetic resonance imaging (MRI) to explore the effects of intracranial artery hemodynamics on SCD in patients with CSVD.MethodsThis study enrolled 40 patients with CSVD, comprising 20 individuals with SCD and 20 with normal cognition. SCD was evaluated according to established diagnostic criteria using the 9-item Subjective Cognitive Decline Questionnaire (SCD-Q9). Hemodynamic parameters, including PI-flow, PI-area, RI and WSS, were measured in nine major intracranial arteries via 4D flow MRI. Associations between these parameters and cognitive status were examined using logistic regression analysis.ResultsCompared to the cognitively normal group, patients with CSVD and concomitant SCD showed lower arterial elasticity at the C7 segment and the basilar artery (BA), and lower WSS at the C2 segment. Logistic regression analysis further identified abnormal RI-BA was independently associated with SCD in the CSVD cohort.ConclusionAltered intracranial artery hemodynamics in patients with CSVD are associated with the presence of SCD. These findings offer mechanistic insight into early cognitive impairment in CSVD and suggest that hemodynamic abnormalities may serve as potential indicators of early cognitive dysfunction in this population.
Burned aggression: the relationship between burnout and aggressive behaviour among young adults in Czechia
IntroductionDespite stress being a critical component of burnout, few studies have investigated the relationship between burnout and aggressive behaviour. Therefore, the current study aims to verify whether states of exhaustion are associated with aggression.MethodsStructural equation models were constructed using data from a representative sample of 1027 young adults (Mage = 24.53), almost half of whom were men (n = 507). The models revealed the relationships between burnout, aggressive behaviour, emotion regulation strategies, risky alcohol consumption, stress, and adverse childhood experiences. ResultsAlthough there were minor differences in the pathways between men and women, both models showed a good fit for the data. Furthermore, among both men and women, the positive relationship between burnout and aggressive behaviour was mediated by maladaptive coping strategies and risky alcohol consumption. Interestingly, reliance on maladaptive emotion regulation strategies was also associated with increased depressive symptoms among women but not among men.ConclusionThe findings of this study reveal that aggressive behaviour is another negative consequence of burnout among young adults and highlight the importance of skills applied in responses to chronic stress. The implications of these findings and further results are discussed in relation to the existing literature.
The relationship between mobile phone addiction and depression, anxiety among Chinese college students: the mediating role of friendship quality and the moderating effect of preference for solitude
BackgroundThe university stage represents a critical period for the development of individual mental health. Mobile phone addiction is closely linked to depression and anxiety among college students, and both friendship quality and preference for solitude are tightly associated with college students’ mobile phone addiction and emotional health. Therefore, this study aimed to investigate the relationships and internal mechanisms among mobile phone addiction, friendship quality, preference for solitude, depression and anxiety in college students.MethodsA total of 1083 Chinese college students (58.2% female; mean age = 19.87 ± 1.692 years) were included as participants. Data were collected using the Mobile Phone Addiction Index, Friendship Quality Questionnaire, Preference for Solitude Questionnaire, and Depression Anxiety Stress Scale. Data processing and analyses were conducted using SPSS 26.0 and the PROCESS macro.Results(1) Mobile phone addiction was significantly negatively correlated with friendship quality, and significantly positively correlated with both depression and anxiety; friendship quality was significantly negatively correlated with depression and anxiety; preference for solitude was significantly positively correlated with depression and anxiety. (2) Mobile phone addiction not only directly and positively predicted depression and anxiety among college students, but also predicted depression and anxiety through the mediating role of friendship quality. (3) The direct effect of mobile phone addiction on depression and the mediating effect of friendship quality in the relationships between mobile phone addiction and depression/anxiety were both moderated by preference for solitude, whereas the moderating effect of preference for solitude on the association between mobile phone addiction and anxiety was not significant.ConclusionFriendship quality serves as an important mediating pathway between mobile phone addiction and depressive and anxiety symptoms among Chinese college students. Preference for solitude may amplify the associations of mobile phone addiction with poorer friendship quality and elevated depressive symptoms.
Collaborative care treatment for major depressive disorder
IntroductionMajor Depressive Disorder (MDD) is a burdensome behavioral health condition that is costly and difficult to treat, particularly for patients with severe cases. The Collaborative Care Model (CoCM) has been shown to be effective for moderate depression treatment but less is known about its effectiveness for severe depression. This study analyzes the impact of CoCM treatment on outcomes for depression patients across all ranges of MDD severity at Concert Health.Materials and methodsAnalysis was completed utilizing all closed patient treatment episodes (N = 30,162) at Concert Health between 2018 and 2025. Of these patients, 5,693 began treatment with severe depression. We compare effect sizes for change between baseline and final screener scores across severity levels. Additionally, we utilize logistic regression to complete analyses to understand treatment factors and patient characteristics that are associated with treatment response and remission, as measured by changes in PHQ-9 scores.ResultsThe primary analysis showed that patients with severe depression (PHQ-9 > 20) had slightly lower odds of achieving response compared to patients with moderate depression (OR: 0.93). The treatment factors of insurance type, suicide risk, anxiety presence, and touchpoints also had significant effects on the odds of achieving response and remission.DiscussionThe results suggest that CoCM may be effective for patients with severe depression in achieving treatment response. Patients on Medicaid or with more complex conditions such as anxiety presence or elevated risk for suicide may need higher levels of engagement from the care team to achieve response and remission.
Smoking as a correlate of suicidal behavior and self-harm in adolescents with depressive disorders
Suicidal behavior and self-harm are major public health concerns among adolescents, particularly those with depressive disorders. While smoking has been linked to suicidality in general populations, its independent role in both suicidal behavior and self-harm within well-characterized clinical samples of youth with depressive disorders remains understudied. This study consecutively enrolled 2,343 adolescents (aged 12–18 years) diagnosed with unipolar depression, bipolar disorder, or depressive episode according to DSM-5 criteria at Nanhai Public Health Hospital of Foshan City and The Third People’s Hospital of Foshan between January 2025 and December 2025. Suicidal behavior (≥1 suicide attempt) and self-harm (intentional self-injury or poisoning regardless of intent) were assessed via clinical interviews. Multivariable binary logistic regression models were constructed to identify factors independently associated with each outcome, adjusting for age, sex, education, income, parental education, psychiatric diagnosis, family history of mental illness, physical disease, and smoking status. Among 2,343 participants (mean age 14.99 ± 1.65 years; 77.8% female), the prevalence of self-harm was 76.0% and suicidal behavior was 44.2%. In fully adjusted models, smoking status was the only variable significantly associated with suicidal behavior after adjustment for measured covariates: current smokers (OR = 2.74, 95% CI: 1.81–4.22, P<0.001) and past quitters (OR = 2.32, 95% CI: 1.66–3.28, P<0.001) had higher odds compared to never smokers. For self-harm, current smoking was significantly associated with increased risk (OR = 2.31, 95% CI: 1.33–4.37, P = 0.006). Education level showed a borderline association with self-harm, with each additional year of schooling corresponding to a 10% lower odds (OR = 0.90, 95% CI: 0.81–1.00, P = 0.050); however, this finding should be interpreted cautiously given the exploratory nature of the analysis. No other demographic or clinical variables, including age, sex, or psychiatric diagnosis, were independently associated with either outcome. Smoking was strongly associated with both suicidal behavior and self−harm after adjustment for measured demographic and clinical covariates. These findings underscore the importance of assessing tobacco use as a potential clinical marker of vulnerability in youth mental health settings.
Association of oxidative stress, metacognition, and psychopathology in patients with schizophrenia: a case-control study
BackgroundMetacognitive deficits are common in schizophrenia (SZ) and may worsen symptoms and impair insight. Oxidative stress (OS) abnormalities have also been reported, but findings are inconsistent, and no study has examined their associations with metacognition and psychopathology.MethodsThis case-control study included 89 SZ patients and 90 healthy controls (HC). OS markers, including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GPX) were measured. The patient group and healthy control group underwent metacognition was assessed using the abbreviated Metacognitive Assessment Scale (MAS-A) and patients’ symptoms with the Positive and Negative Syndrome Scale (PANSS). Covariates included age, gender, education, BMI, and smoking, illness duration, onset age and medication.ResultsPatients showed significantly lower MAS-A total score and subscale scores (all p < 0.01) versus HC. Patients had lower SOD, CAT and GPX (130.69 vs 152.12 ng/L, 2.46 vs 6.62 ng/L, 158.09vs 197.75μmol/L) and higher MDA (9.22vs 7.34μmol/L) than controls (all p < 0.05). Partial correlation revealed that in patients: SOD was negatively correlated with positive/negative/PANSS total and MAS-A decentration scores; CAT was negatively correlated with general pathological/PANSS total scores, and positively correlated with MAS-A total score and its subscales (self-reflectivity, understanding the other’s mind, decentration, mastery), MDA was negatively correlated with negative symptom score and self-reflectivity score, and positively correlated with general pathological score; GPX was positively correlated with most clinical and metacognitive scores. Linear regression revealed SOD, CAT, and GPX significantly associated with the PANSS total score (β = -0.119, -6.169, -0.226; all p < 0.05), and with MAS-A total score (β = 0.021,2.879 0.049, all p < 0.001).ConclusionSchizophrenia patients exhibit OS abnormalities and metacognitive impairments. Greater OS severity correlates with worse metacognition and more severe psychopathology, suggesting OS as a key factor linking these domains.
A genome-scale CRISPRi perturbation atlas of human induced pluripotent stem cells
Nature Biotechnology, Published online: 01 July 2026; doi:10.1038/s41587-026-03199-w
A transcriptional regulatory map of pluripotent stem cells is generated by CRISPR screening.
Blood-based circular RNAs for early diagnosis of Alzheimer’s disease
Nature Medicine, Published online: 01 July 2026; doi:10.1038/s41591-026-04485-5
Tested in large cohorts, a predictive model including 34 blood circular RNAs predicts progression to symptomatic AD, outperforming pTau217 and amyloid-PET.