This study aimed to evaluate the clinical efficacy of acupuncture combined with gradual benzodiazepine dose reduction in patients with benzodiazepine-dependent insomnia (BDI) and to assess associated withdrawal outcomes.

A total of 64 patients with BDI were randomly assigned to either the acupuncture plus gradual benzodiazepine reduction group (ARB, n = 32) or the placebo acupuncture plus gradual benzodiazepine reduction group (PARB, n = 32). Treatments were administered five times per week for 4 weeks, followed by an 8-week observation period. The primary outcomes were changes in Insomnia Severity Index (ISI) scores and the drug reduction rate of benzodiazepines (DRRB). Secondary outcomes included the rate of successful discontinuation and scores on the Fatigue Scale-14 (FS-14).

Sixty-three patients completed the trial (ARB group, n = 32; PARB group, n = 31). Patients in the ARB group demonstrated significantly greater reductions in ISI scores compared with those in the PARB group (p = 0.005 for week 4-week 0 and week 12-week 0 comparisons). The DRRB was also significantly higher in the ARB group compared with the PARB group (p = 0.002 for week 4-week 1 and p < 0.001 for week 12-week 1). At week 12, the ARB group additionally demonstrated lower FS-14 scores and a higher rate of successful benzodiazepine discontinuation.

Acupuncture combined with gradual benzodiazepine reduction significantly reduced insomnia severity and promoted benzodiazepine discontinuation in patients with BDI.

Nucleobase-containing peptides (nucleopeptides) represent a unique class of biohybrid molecules that combine the structural versatility of peptides with the functional properties of nucleobases, enabling programmable self-assembly and selective molecular interactions. These features position nucleopeptides as promising tools for biomedical and supramolecular applications. Here, we report the synthesis and characterization of a novel nucleopeptide derived from a tryptophan dipeptide (WW) functionalized with a thymine (T) base, termed WWT. Circular Dichroism and UV-Vis spectroscopy revealed distinctive spectral features and supramolecular organization in solution, confirmed by Dynamic Light Scattering. Binding studies showed no detectable interaction with DNA or RNA, whereas measurable spectral perturbations indicated affinity for bovine serum albumin. Metal-binding experiments with Ni(II) and Cu(II) further highlighted the influence of these ions on the modulation of WWT's optical properties, while computational modelling using HDOCK complemented the experimental data by predicting aggregation modes and protein-binding interfaces. To explore biological relevance, we integrated controlled exposure of IMR-90 human fibroblasts and Jurkat T lymphocytes with proteomics and metabolomics, identifying time-dependent modulation of pathways linked to metabolism, RNA/DNA processing, and T-cell signaling. Functionally, WWT enhanced fibroblast migration without altering lysosomal, mitochondrial, or cytoskeletal organization. Overall, this study provides the first combined synthetic, spectroscopic, computational, and multi-omics evaluation of WWT properties and effects, revealing its organized supramolecular behaviour, selective biomolecular interactions, and potential pro-regenerative properties.

Obsessive-compulsive disorder (OCD) frequently emerges during adolescence, a critical period for the development of static and dynamic properties of large-scale brain networks. Although previous studies have reported altered static connectivity in adolescents with OCD, the temporal organization of functional networks during this stage remains largely unexplored.

We analyzed resting-state fMRI data from 40 adolescents with OCD and 40 age- and sex-matched healthy controls. Group independent component analysis (ICA) was used to identify intrinsic connectivity networks (ICNs). A sliding-window approach and k-means clustering were applied to derive dynamic brain states, while graph-theoretical metrics (strength, local efficiency, clustering coefficient) were computed to assess nodal variability over time. Group comparisons were performed using general linear models controlling for age and sex, and symptom correlations were tested using partial correlation analyses.

Compared to controls, OCD patients spent significantly less time in a globally integrated brain state characterized by strong intra- and inter-network connectivity. At the local level, reduced temporal variability was observed in the striatum, thalamus, and dorsolateral prefrontal cortex, key nodes of the cortico-striato-thalamo-cortical (CSTC) circuit. Notably, reduced striatal variability correlated with greater OCD symptom severity and decreased time in the integrated brain state.

These findings reveal disrupted dynamic network integration and reduced functional flexibility in adolescents with OCD, both globally and locally. This multilayered impairment may reflect early pathophysiological mechanisms and offers potential targets for age-sensitive neuromodulation strategies.

ChiCTR2400092275, Chinese Clinical Trial Registry (www.chictr.org.cn).

Pre-frailty is a high-risk state prevalent in older adults, representing a critical window for intervention. Pickleball, a popular paddle sport, offers a unique blend of physical activity and social engagement, but its efficacy in reversing pre-frailty remains understudied. This study aimed to investigate the effects of an 8-week pickleball training program on pre-frailty, physical fitness, 24-hour movement behaviors, and quality of life in community-dwelling older adults.

72 older adults [age: median (interquartile range) = 67 (5)] with pre-frailty were randomly assigned to either a pickleball intervention group (n = 36) or a control group (n = 36). The pickleball group participated in supervised 8-week pickleball sessions, while the control group maintained their usual lifestyle. Outcomes included frailty status, functional fitness, 24-hour movement behaviors (assessed using accelerometers and compositional data analysis), and quality of life. Analyses followed an intention-to-treat principle with multiple imputation for missing data. Between-group differences in pre-frailty reversal rates were assessed using Fisher's exact test and absolute recovery increase. Generalized estimating equation models were used to evaluate Group × Time interactions for outcomes.

After 8 weeks, 42% of the pickleball group transitioned from pre-frailty to non-frailty, compared to 8% in the control group (p < 0.001). Statistically significant improvements were observed in functional fitness, including the 30-second chair stand [β = 4.89, p < 0.001], 30-second arm curl [β = 3.70, p < 0.001], back scratch [β = 3.27, p = 0.003], and 6-minute walk distance [β = 31.10, p = 0.041]. Quality of life improved for both physical [β = 2.37, p = 0.040] and mental health scores [β = 4.83, p = 0.001]. Compositional data analysis showed a favorable shift in movement behaviors, with reduced sedentary time [β = -37.19, p = 0.028] and increased light physical activity [β = 17.43, p = 0.033] in the pickleball group.

An 8-week pickleball intervention effectively reversed pre-frailty, improved functional fitness, and enhanced quality of life. These findings suggest pickleball as a promising exercise for preventing frailty and promoting healthy aging.

Chinese Clinical Trial Registry ChiCTR2500098832. Registered March 13, 2025.

Mild traumatic brain injury (mTBI) is often considered low risk, yet growing evidence suggests that outcomes may differ by sex, and when explored, also by gender. We examined sex-associated differences in structural injury, acute-care complications, and neuropsychiatric diagnoses for patients with mTBI.

This retrospective cohort study used the TriNetX Global Health Research Network to identify adults (≥18 years) diagnosed with mTBI (Glasgow Coma Scale 13-15) between 2010 and 2022. Patients were identified using ICD-10 codes (S06, S09, R40.2411-R40.2413), with exclusion of moderate and severe TBI. Outcomes were assessed at 1 month, 6 months, 1 year, and 2 years. Propensity score matching (1:1) was performed to balance demographic and clinical characteristics. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression.

Among 26,829 patients with mTBI, 9,999 (37.3%) were female and 16,830 (62.7%) were male. After matching, 9,649 patients remained in each cohort. Female patients had significantly lower odds of intracranial lesions, including epidural hematoma (OR 0.59, 95% CI 0.46-0.76) and subdural hematoma (OR 0.79, 95% CI 0.73-0.87), as well as lower odds of mortality, intensive care unit admission, neurosurgical intervention, and systemic complications across follow-up. In contrast, females demonstrated higher odds of anxiety (OR range 1.86-1.95) and depression (OR range 1.63-1.81) at all time points.

In this large cohort, women with mTBI exhibited lower structural and acute-care burden but higher long-term neuropsychiatric sequelae. These findings highlight the importance of sex- and gender-informed approaches to acute risk stratification and longitudinal mental health follow-up after mTBI.

Stress engages coordinated psychological, neuroendocrine, autonomic, and neural processes that enable adaptation to environmental demands but may contribute to vulnerability when stress is prolonged, uncontrollable, or socially evaluative. Functional neuroimaging has become central to psychoneuroendocrinology by enabling direct investigation of how acute stress shapes brain activation and connectivity and how these neural responses interact with hypothalamic-pituitary-adrenal axis regulation. This editorial introduces the Special Issue "Effects of stress on brain activation changes: Recent developments" and outlines key conceptual and methodological advances in the field. We highlight progress from endocrine-marker-based stress research toward brain-based models of stress, emphasizing evidence from scanner-based paradigms such as the Montreal Imaging Stress Task and ScanSTRESS, as well as emerging multimodal approaches including fNIRS, PET, EEG, and harmonized large-scale analyses. We discuss recent developments concerning exposure-time effects, network-level models of stress processing, and the importance of functional connectivity. We further emphasize the need to account for individual and contextual variability, including sex, gender, developmental stage, clinical vulnerability, and real-world stress relevance. This Special Issue invites contributions that use neuroimaging to advance mechanistic, translational, and reproducible models of stress-related brain function.

Cognitive reappraisal (CR) is one of the most widely studied emotion regulation strategies and is considered central to psychological well-being. Given its protective role in mental health, a growing body of research has examined factors that influence the effectiveness of CR. However, prior studies have been conducted in controlled settings, typically relying on standardized, laboratory-induced stressors, which may limit ecological validity of the findings. The present study aimed to address this gap by investigating CR in the context of real-world stressors. We recruited 100 young adults who used a mobile application, ReApp, to record their daily stressors and practice CR three times per day, over a three-week period. Our findings suggest that the effectiveness of CR is highly context-dependent, and certain aspects may be more relevant and contributing to CR effectiveness than the other. Specifically, higher positive affect and greater stressor severity were associated with more effective CR. By contrast, higher negative affect and lower reappraisal affordance predicted reduced CR effectiveness. We provide the first evidence that CR effectiveness varies across stressor domains, suggesting it may be better suited to some types of real-world stressors (i.e., health-related stressors) than others (i.e., lack of resources). In contrast, neither subjective stress nor the time spent on generating reappraisals influenced CR effectiveness. Being one of the first outside-laboratory study examining contextual factors contributing to CR effectiveness, these results carry clinical implications, suggesting that CR trainings may be optimized by adjusting practice to specific contextual factors, and warrant the need for further research.

The aim of this study was to identify the optimal stimulation sites for subthalamic nucleus (STN) deep brain stimulation (DBS) in treating Meige syndrome using long-term follow-up data from a large sample cohort, evaluate the whole-brain functional connectivity patterns associated with favorable treatment responses, and validate these findings in an independent cohort.

The authors retrospectively analyzed long-term outcomes in 65 patients with Meige syndrome who underwent bilateral STN-DBS in two centers. The local stimulation effects within the STN and the distributed functional connectivity associated with motor improvement were investigated using advanced imaging and modeling tools, including the Lead-Group Toolbox, DBS Sweet Spot Mapping Explorers, and DBS Network Mapping Explorers. To ensure the model's reliability and generalizability, both internal validation through multiple cross-validation strategies and external validation using independent cohorts were conducted.

STN-DBS yielded significant and sustained motor improvements in both cohorts, with mean Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement score reductions of 63% in the training cohort (n = 50) and 56% in the validation cohort (n = 15) (p < 0.001). At the local level, the optimal stimulation sites were consistently located in the dorsolateral sensorimotor subregion of the STN, extending bilaterally toward the associative subregion and centered at MNI coordinates x = ±12, y = -13, z = -6. At the network level, favorable outcomes were primarily associated with positive functional connectivity to the cerebellum and negative connectivity to the somatosensory cortex. Both the sweet spot and connectivity models developed using the training cohort showed significant correlations with clinical outcomes in the independent validation cohort (R = 0.59, p = 0.020; R = 0.74, p = 0.002, respectively) and remained robust across different cross-validation strategies.

The optimal therapeutic efficacy of STN-DBS for Meige syndrome depends on precise targeting within the dorsolateral STN and modulation of a distributed functional network involving the cerebellum and sensorimotor cortex. These findings may aid in developing personalized targeting strategies and adaptive programming paradigms, ultimately improving the therapeutic efficacy of DBS in this challenging disorder.

Trigeminal neuralgia is a debilitating facial pain condition. Managing trigeminal neuralgia in patients with co-existing conditions like idiopathic thrombocytopenic purpura, which increases bleeding risk, presents a significant clinical challenge, especially when considering interventional procedures.

We present the case of a 54-year-old woman with refractory right-sided trigeminal neuralgia and idiopathic thrombocytopenic purpura. Due to her idiopathic thrombocytopenic purpura and a new acute cerebrovascular accident, she was not a candidate for microvascular decompression. Initial gamma knife treatment provided only transient relief. Because of her bleeding risk, less invasive peripheral trigeminal branch blocks were performed, followed by cryoneurolysis of the infraorbital and mental nerves, which provided significant and sustained pain relief for 11 months.

This case highlights that for patients with trigeminal neuralgia who have a high bleeding risk due to conditions like idiopathic thrombocytopenic purpura, peripheral trigeminal branch blocks under ultrasound guidance, followed by cryoneurolysis, can be a safe and effective alternative to more invasive procedures, offering long-lasting pain relief.

Importance: At present, the diagnoses of many psychiatric and neurological disorders are based on clinical symptoms and behaviors, neglecting the laboratory test indicators. This narrative review assessed the existing published literature on the role of microRNAs (miRNAs) in psychiatric and neurological disorders. Observations: The miRNAs are involved in numerous biological processes, and their dysregulation can lead to neuropsychiatric disorders. They also play a prominent role in neurotransmitter signaling pathways, and their impairment can lead to psychiatric disorders. The miRNAs act as key regulators of neuronal functions such as neuroplasticity, differentiation, and protection of neurons and also play a role in establishing memory and cognition. Neurodegenerative processes therefore involve miRNAs as potential targets for treatment and early detection. The functional regulation of miRNAs of several genes has made miRNAs potent targets for therapeutic development. Conclusions and Relevance: miRNAs have the potential to be used as biomarkers for diagnosis and treatment response in psychiatric and neurological disorders. Prim Care Companion CNS Disord 2026;28(2):25nr04069. Author affiliations are listed at the end of this article.