BackgroundPost-translational modifications, particularly SUMOylation, plays a crucial role in α-synuclein (α-syn) aggregation, a key pathological feature of Parkinson’s disease (PD). Curcumin, a natural polyphenol, has shown neuroprotective potential, but its effects on SUMOylation-related signaling in PD remain unclear.ObjectiveThis study aimed to investigate whether curcumin modulates α-syn SUMOylation and to elucidate the underlying molecular mechanisms in PD model mice.MethodsA PD model was established in male C57BL/6 mice via unilateral intrastriatal injection of α-syn preformed fibrils (PFFs). Six months after α-syn PFFs injection, mice were treated intravenously with curcumin (25 mg/kg/day) or vehicle for 1 month. Behavioral tests (open field, rotarod) assessed motor function. Neuropathology was evaluated by immunohistochemistry and western blotting for tyrosine hydroxylase (TH), phosphorylated α-syn (p-syn), SUMOylation pathway components (SUMO1, SAE2, UBC9, PIAS1/2), and ubiquitin. Striatal dopamine levels were measured by HPLC.ResultsCurcumin treatment ameliorated motor deficits and anxiety-like behaviors in PD mice. It partially preserved dopaminergic neurons and reduced p-syn aggregation in the substantia nigra, accompanied by increased striatal dopamine levels. Mechanistically, curcumin was associated with reduced SUMO1 and increased ubiquitin levels, suggesting modulation of SUMOylation-related signaling. Among SUMOylation enzymes, UBC9 expression was decreased, whereas E1 (SAE2) and E3 (PIAS1/2) components were not substantially affected.ConclusionOur findings demonstrated that curcumin exerted neuroprotective effects in a PD model by attenuating α-syn pathology. The protective mechanism involves the inhibition of α-syn SUMOylation, primarily through the downregulation of the UBC9 enzyme. This study identifies UBC9-mediated SUMOylation as a potential target for curcumin and highlight a promising strategy for modifying α-syn-associated pathology in PD.
Targeting mitochondria for the treatment of neurodegenerative diseases
Mitochondria are central regulators of cellular metabolism, redox balance, calcium signaling, and cell survival, making them essential for neuronal function. Because neurons rely heavily on mitochondrial oxidative phosphorylation to meet their high energetic demands, mitochondrial dysfunction has emerged as a key pathogenic driver in major neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Defects in mitochondrial bioenergetics, excessive reactive oxygen species production, impaired mitochondrial dynamics, disrupted mitophagy, and dysregulated calcium handling collectively contribute to neuronal damage, synaptic dysfunction, and neuroinflammation. These insights have prompted growing interest in therapeutic strategies that directly target mitochondria to restore organelle homeostasis. Recent advances in chemical biology and nanomedicine have enabled the development of mitochondria-targeted ligands, peptide-based targeting systems, and carrier or nanotechnology-enabled delivery platforms designed to overcome biological barriers and selectively deliver therapeutic cargos to mitochondria within the central nervous system. In this Review, we summarize mitochondrial pathological mechanisms in neurodegenerative diseases and discuss emerging mitochondria-targeted therapeutic strategies, highlighting delivery technologies, therapeutic modalities, and translational challenges. Although most strategies remain at the preclinical or proof-of-principle stage, these advances are beginning to shape a conceptual framework for precision mitochondrial medicine, with the longer-term goal of developing disease-modifying interventions for neurodegenerative disorders.
Venous-significant intracranial hemorrhage in neonatal HIE treated with therapeutic hypothermia: imaging phenotypes, diagnostic pitfalls, and prognostic implications
In the therapeutic hypothermia era, intracranial hemorrhage is increasingly detected in term and near-term neonates with hypoxic–ischemic encephalopathy (HIE), yet its clinical significance remains heterogeneous and is often oversimplified. This review uses a pattern-based approach for venous system–related intracranial hemorrhage in neonatal HIE, with particular emphasis on cerebral sinovenous thrombosis (CSVT) and hemorrhagic venous infarction. Magnetic resonance imaging plays a central role in etiologic assessment, with diffusion-weighted imaging and susceptibility-weighted imaging providing the core parenchymal and hemorrhagic information, while MR venography is most informative when imaging features raise suspicion for venous involvement. Imaging phenotypes that should prompt venous reconsideration include hemorrhagic parenchymal lesions crossing arterial territories and intraventricular hemorrhage accompanied by unilateral thalamic or deep parenchymal hemorrhage. Common pitfalls in neonatal MR venography interpretation–particularly flow-related artifacts–are also highlighted, emphasizing the importance of parenchymal–venographic concordance in avoiding both over- and underdiagnosis of CSVT. Mechanistically, hypoxia–reperfusion injury, endothelial activation, venous stasis, and developmental hemostatic vulnerability may create a milieu in which thrombosis and hemorrhage coexist. Available evidence suggests that long-term outcomes are driven more by associated venous-related parenchymal injury than by small-volume hemorrhage alone, underscoring the importance of pattern-guided imaging interpretation and follow-up.
Subcortical gray matter atrophy and iron deposition in patients with vascular dementia: a multimodal MRI study
PurposeVascular dementia (VAD) is the second most common type of dementia worldwide. Therefore, early detection and diagnosis, along with a clear understanding of its pathogenesis are critical for mitigating disease progression. In the present study, we aimed to elucidate the associations of brain volume and iron deposition with VAD based on structural brain and iron content analyses.MethodsFifty-three patients with VAD and 43 control participants were recruited for this study. All participants underwent the Mini-Mental State Examination (MMSE) and brain MRI scans. This study primarily focused on the volume of specific brain regions (assessed using FreeSurfer) and iron deposition (evaluated using quantitative susceptibility mapping [QSM]). Linear regression analysis was also performed.ResultsPatients with VAD exhibited significant reductions in brain volume in the left putamen (β = −0.342, 95% CI: −0.581 to −0.104), left pallidum (β = −0.099, 95% CI: −0.187 to −0.001), left hippocampus (β = −0.138, 95% CI: −0.271 to −0.004), and right hippocampus (β = −0.235, 95% CI: −0.420 to −0.051). Additionally, significant increases in iron levels were identified in the left (β = 0.006, 95% CI: 0.002 to 0.010) and right (β = 0.005, 95% CI: 0.001 to 0.009) hippocampus.ConclusionsThese findings indicate that brain volume reduction and increased iron levels in specific regions may be associated with cognitive deficits in patients with VAD.
Editorial: Emerging treatment approaches for substance use disorders
Editorial: eHealth and personalized medicine in mental health and neurodevelopmental disorders: digital innovation for diagnosis, care, and clinical management
Illness perception, family resilience, and emotional distress among hospitalized older adults with multimorbidity in Xinjiang, China: a latent profile and mediation analysis
BackgroundOlder adults with multimorbidity frequently encounter significant psychological challenges, with negative illness perception being a prevalent issue. Such perceptions can intensify emotional distress. Family resilience—the ability of a family system to adapt positively to adversity—plays a crucial role in alleviating negative emotions, including anxiety and depression. This study aimed to investigate the heterogeneity of illness perception among older patients with multimorbidity and to assess the mediating effect of family resilience on the relationship between illness perception and emotional distress.Materials and MethodsBetween October 2025 and January 2026, 420 multimorbid older patients were recruited in three tertiary hospitals of Xinjiang Province. The evaluation was done based on the Brief Illness Perception Questionnaire, the Chinese version of the Family Resilience Assessment Scale, and the Hospital Anxiety and Depression Scale. The two methods of analysis were the latent profile analysis used to determine the unique patterns of illness perception and the bootstrap-based mediation analysis to determine whether family resilience mediates.ResultsThree distinct illness perception profiles were identified: low (32.6%), moderate (47.6%), and high (19.8%) illness perceptions. Using the low illness perception group as the reference, family resilience showed a significant partial mediating effect between moderate illness perception and anxiety (indirect effect = 0.510, 95% CI: 0.325–0.724), moderate illness perception and depression (indirect effect = 0.450, 95% CI: 0.283–0.631), high illness perception and anxiety (indirect effect = 1.263, 95% CI: 0.819–1.739), and high illness perception and depression (indirect effect = 1.114, 95% CI: 0.707–1.555).DiscussionThe results demonstrated heterogeneity in the perception of illness among older multimorbid patients, as a substantial percentage of the sample had moderate-to-high levels. Family resilience played a major partial mediating role between illness perception and emotional distress. The findings suggest the significance of shifting the clinical emphasis to the family system and integrating family resilience improvement as one of the psychological support measures for chronic patients.
Latest developments in the use of e-cigarettes by people with schizophrenia spectrum disorders who smoke: a scoping review
BackgroundTobacco use is significantly more prevalent among individuals with schizophrenia spectrum disorders (SSD) compared to the general population, contributing to elevated rates of premature mortality from smoking-related diseases. Despite a decline in smoking prevalence in the general population, individuals with SSD continue to smoke at persistently high rates, driven by biological, psychological, and social factors. Standard smoking cessation approaches yield markedly poorer outcomes in this group compared to non-psychiatric populations. This scoping review aimed to map the emerging evidence on the use of e-cigarettes among individuals with SSD or serious mental illness (SMI).MethodsThis scoping review was conducted in accordance with the Population–Concept–Context (PCC) framework and reported following the PRISMA extension for Scoping Reviews (PRISMA-ScR) guidelines. The review focused on studies published between January 2020 and February 2026, searched on PubMed and EMBASE, providing an up-to-date synthesis of emerging evidence on e-cigarette use in this vulnerable population.ResultsThree studies reported across four publications were included (total N = 323); one research group (Pratt et al.) contributed two separate publications reporting distinct outcomes from the same study cohort. Findings suggest that e-cigarette-based interventions are feasible and acceptable in individuals with SSD and SMI, with preliminary evidence of smoking reduction and decreased exposure to tobacco-related carcinogens. However, sustained harm reduction appeared dependent on a combined approach considering that device provision was empowered in its efficacy to sustain harm reduction over time when integrated with behavioral support.ConclusionsThe available evidence, while preliminary and limited by the small number of included studies, should be interpreted with caution regarding generalizability to patients with Schizophrenia Spectrum Disorders exclusively, as three of the four included publications recruited participants with broader SMI diagnoses of which SSD represents only a subset. Further research, including larger adequately powered trials with standardized outcome measures and longer follow-up, is needed to establish the generalizability and long-term impact of these interventions.
Remimazolam versus propofol on seizure adequacy in electroconvulsive therapy: a retrospective cohort study
ObjectiveElectroconvulsive therapy (ECT) is a core treatment modality for severe mental disorders, and the choice of anesthetic induction agent directly impacts seizure quality and therapeutic outcomes. This study aimed to compare the effects of remimazolam versus propofol on seizure adequacy during ECT.MethodsThis retrospective secondary analysis was conducted using data from a prospective observational cohort. A total of 859 ECT sessions from 114 patients were included. The primary outcome was the rate of adequate seizure, defined as an electroencephalographic (EEG) ictal duration of ≥15 seconds. Secondary outcomes included EEG seizure duration, post-ictal suppression index (PSI), maximum sustained power (MSP), and average seizure energy index (ASEI). Stabilized inverse probability of treatment weighting was employed to balance baseline covariates between groups, with balance assessed by standardized mean differences. Generalized linear mixed models were used to compare intergroup differences, accounting for random effects at the patient level. Subgroup analysis, E-value calculation, and propensity score matching (PSM) at 1:1 and 1:2 ratios were performed as sensitivity analyses to assess the robustness of the results. ResultsA total of 859 ECT sessions were included, with 179 in the remimazolam group and 680 in the propofol group. Baseline characteristics were well-balanced between groups after weighting. The remimazolam group exhibited a significantly higher rate of adequate seizures compared with the propofol group (adjusted odds ratio: 12.054, 95% confidence interval: 5.758–25.233, P < 0.001), along with prolonged EEG seizure duration and elevated MSP. No significant between-group differences were observed in PSI or ASEI. The results of all sensitivity analyses were consistent with those of the primary analysis.ConclusionRemimazolam was associated with a higher rate of EEG seizure adequacy and longer EEG seizure duration; however, whether this electrophysiological advantage translates into better clinical outcomes remains to be investigated in prospective studies.
ENVnet provides a global molecular resource of dissolved organic matter
Nature Biotechnology, Published online: 21 July 2026; doi:10.1038/s41587-026-03230-0
A resource of dissolved organic matter illuminates carbon and microbial life in Earth’s ecosystems.