In recent years, the comorbidity of major depressive disorder (MDD) and attention deficit hyperactivity disorder (ADHD) has received increasing attention. In adult patients, MDD comorbid with ADHD usually implies high treatment costs, poor drug response, and an unfavorable disease prognosis. However, there are certain limitations in current drug therapies. As executive dysfunction is a key shared feature of MDD and ADHD, it is of great importance to explore the potential mechanisms of this comorbidity in terms of neuroimaging and to seek more effective treatment methods from the perspective of executive function. Research in recent years has shown that transcranial direct current stimulation (tDCS), a non-invasive physical therapy capable of regulating the activity of specific brain regions, can effectively improve relevant symptoms of MDD and adult ADHD. This article aims to review the treatment dilemmas faced by adult patients with MDD comorbid with ADHD, summarize the possible mechanisms underlying this comorbidity from multiple dimensions, such as brain structure and functional networks related to executive function, and simultaneously explore the application prospects of tDCS in the treatment of adult MDD comorbid with ADHD.

Chemodynamic therapy (CDT) is severely limited by inadequate intracellular H2O2 and frequent apoptosis resistance. Herein, a porous Fe3O4 nanoplatform is engineered through coating of Fe3 +-tannic acid complex onto nanoclusters simultaneously loaded with carbonyl cyanide 3-chlorophenylhydrazone (CCCP, a mitochondrial uncoupler) and lactate oxidase (LOD). By self-supplying H2O2 and concurrently blocking autophagic flux, this system is engineered to potentiate CDT efficacy. Beyond the expected therapeutic outcome, we uncover that this nanoplatform triggers an unconventional cell death pathway-paraptosis. Acid-triggered dissociation in the tumor microenvironment releases Fe2 +/Fe3 + for Fenton reactions while LOD simultaneously converts lactate to H2O2, overcoming the H2O2 bottleneck. CCCP further synergizes this process by collapsing the mitochondrial membrane potential, which amplifies ROS leakage and culminates in an oxidative storm. This dramatic surge in ROS directly induces mitochondrial dysfunction and initiates endoplasmic reticulum stress, while also suppressing autophagic flux. Collectively, these multi-organelle stresses markedly exacerbate intracellular damage and lead to paraptotic cell death, characterized by extensive cytoplasmic vacuolization, eliciting robust immunogenic cell death. Combined with αPD-L1, the nanoplatform potently activates antitumor immunity and suppresses both primary and distant tumors. This work pioneers a paraptosis activation strategy driven by an iron-based nanodrug, redefining CDT efficacy through multi-organelle stress synergy for amplified immunotherapy.

Agitation is a common symptom in psychiatric clinical practice,typically accompanied by emotional fluctuations and aggressive behaviors,which significantly impair patients'treatment outcomes and pose safety risks to healthcare providers.Abnormal prefrontal cortex function and various neurotransmitter imbalances are considered the primary biological mechanisms underlying the onset of agitation.Music therapy,as a non-pharmacological intervention,has been shown to effectively alleviate agitation by enhancing brain functional connectivity,modulating neurotransmitter activity,and regulating physiological stress responses.Furthermore,music therapy has demonstrated positive therapeutic effects in clinical applications for patients with specific psychiatric conditions,such as Alzheimer's disease,traumatic brain injury,and schizophrenia.Future research should focus on further elucidating the neurobiological mechanisms by which music therapy mitigates agitation,exploring the integration of multimodal interventions,and evaluating long-term efficacy,in order to facilitate its widespread clinical implementation and continuous optimization.

Simultaneously addressing A ,842 aggregation and oxidative stress within the Alzheimer's disease (AD) microenvironment has emerged as a promising therapeutic strategy for countering the complex pathogenesis of AD. In this study, we developed a multifunctional nanocomposite (GQDs@MPN) with reactive oxygen species scavenging properties. This nanocomposite consists of graphene quantum dots encapsulated within a metal-polyphenol network (GQDs@MPN) formed by physiological Co (II)-coordinated epigallocatechin gallate (EGCG). GQDs@MPN effectively modulates the AD microenvironment by inhibiting A ,842 amyloidosis, attenuating oxidative stress, and regulating microglial activity. In vivo experiments demonstrated that GQDs@MPN, capable of crossing the blood-brain barrier (BBB), significantly reduced A ,842 deposition in APP/PS1 mice. Additionally, GQDs@MPN could exert its anti-inflammatory function by scavenging intracellular ROS and regulating the transformation of microglia from M1 phenotype to M2 phenotype, thus alleviating neuroinflammation. The underlying molecular mechanism is the up-regulation of nuclear factor-erythroid 2-related factor 2 (Nrf2) to clear ROS and subsequently inhibit the nuclear factor KB (NF-KB) signaling pathway. GQDs@MPN also effectively alleviated cognitive impairment and exhibited favorable biocompatibility in APP/PS1 mice. These findings suggest that GQDs@MPN is a promising candidate for multi-targeted AD therapy. We propose that such multifunctional nanocomposites could offer new avenues for developing novel AD inhibitors. (c) 2025 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science & Technology.

Circadian dysregulation is implicated in Major Depressive Disorder (MDD). This study investigated the mediating roles of sleep disturbances and somatic symptoms in the circadian preference-depression relationship and explored moderating effects of NPAS2 variants in 257 MDD patients. The Hamilton Rating Scale for Depression (HAMD-17,17-item clinician-rated measure of depression severity), Morningness-Eveningness Questionnaire (MEQ, circadian preference scale), Pittsburgh Sleep Quality Index (PSQI, sleep quality measure), and Depression and Somatic Symptoms Scale (DSSS, somatic symptom inventory) were obtained in all subjects. Genotypes of single nucleotide polymorphisms (SNPs) of NPAS2 were determined by the PCR and MassArray SNP sequencing analysis. Spearman's correlation, bootstrap mediation, and moderated mediation analyses revealed that sleep disturbances and somatic symptoms sequentially mediated the circadian preference-depression link (preference→sleep: β = -0.075,p = 0.002; sleep→somatic: β = 0.711,p < 0.001; somatic→depression: β = 0.216,p < 0.001). NPAS2 variants moderated these effects: rs3768984 strengthened eveningness-sleep associations (β = 2.944,p < 0.05), while rs3811561 showed similar amplification (β = 3.942,p < 0.05). Rs3768984 additionally moderated the mediation pathway (β = -0.054,95%CI[-0.09,-0.02]). These findings elucidate mechanistic pathways connecting circadian rhythms and MDD, highlighting NPAS2 as a genetic moderator, which may inform targeted interventions. Future studies could explore circadian genetic influences on personalized depression interventions.

AIMS:To characterize the evolution of the burden of Bipolar disorder (BP) from 1990 to 2021 and to forecast trends. METHODS:Based on the Global Burden of Disease (GBD) 2021 study, age-standardized rates (per 100,000 people) of BP incidence, prevalence, and disability-adjusted life years (DALYs) were analyzed from 1990 to 2021, with estimated annual percentage changes (EAPC) calculated. Bayesian age-period-cohort (BAPC) modeling was used to predict incidence trends through 2035. Health inequalities were assessed using the slope index of inequality (SII) and concentration index. RESULTS:Globally, the incidence, prevalence, and DALYs rates of BP increased in 2021 compared to 1990. Regionally, Australasia had the highest age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), and age-standardized death rate (ASDR) in 2021, with New Zealand leading at the country level. Incidence peaks at 15-19 years of age and is significantly higher in females than in males. The BAPC model predicts continued global increases in incidence, prevalence, and DALYs through 2035. Analysis of health inequalities shows that absolute and relative health inequalities are particularly pronounced in countries and regions with higher levels of development. CONCLUSIONS:Overall trends in the burden of BP from 1990 to 2021 show regional and national variations, and global rates of BP incidence, prevalence, and DALYs are projected to continue to rise through 2035. It's urgent to develop targeted prevention and treatment strategies to address this growing global health challenge at the global level, especially in countries and regions with high levels of development.

Objective and quantitative neuroimaging biomarkers are crucial for early diagnosis of major depressive disorder (MDD). However, previous studies using machine learning (ML) to distinguish MDD have often used small sample sizes and overlooked MDD's neural connectome and mechanism. To address these gaps, we applied Dynamic Graph Convolutional Nets (DGCNs) to a large multi-site dataset of 2317 resting state functional MRI (RS-fMRI) scans from 1081 MDD patients and 1236 healthy controls from 16 Rest-meta-MDD consortium sites. Our DGCN model combined with the personal whole brain functional connectivity (FC) network achieved an accuracy of 82.5 % (95 % CI:81.6-83.4 %, AUC:0.869), outperforming other universal ML classifiers. The most prominent domains for classification were mainly in the default mode network, fronto-parietal and cinguloopercular network. Our study supports the stability and efficacy of using DGCN to characterize MDD and demonstrates its potential in enhancing neurobiological comprehension of MDD by detecting clinically related disorders in FC network topologies.

Suicidal ideation, under the dominion of suicidal behavior, represents the most severe consequence of depressive disorders. Overt aggressive behaviors leading to agitated symptoms, coupled with cognitive symptoms during a depressive episode, both impact suicidal ideation and behavior. However, the precise mechanisms by which cognitive symptoms and overt aggressive behaviors influence suicidal ideation in patients with depressive disorders remain unclear. This cross-sectional study analyzed 301 MDD patients from the Shanghai Mental Health Centre between May 2017 and July 2020. Depression severity and cognitive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17), overt aggression with the Modified Overt Aggression Scale (MOAS), and suicidal ideation with the Beck Scale for Suicide Ideation (BSSI). A multivariate logistic regression was conducted to identify risk factors for suicidal ideation. Patients with suicidal ideation had higher levels of cognitive impairment and overt aggression (Z = − 5.527, P < 0.01; Z = − 3.482, P < 0.01). Overt aggressive symptoms positively correlated with suicide ideation (r = 0.177, P = 0.006) and cognitive performance scores (r = 0.173, P = 0.035). And cognitive performance scores also positively correlated with suicide ideation (r = 0.308, P < 0.001). Logistic regression identified cognitive symptoms (OR 1.47) and overt aggression (OR 1.40) as predictors of suicidal ideation in MDD patients (P < 0.05). Mediation analysis revealed that cognitive symptoms mediated the relationship between overt aggression and suicidal ideation (indirect effect: 0.1903). In MDD, cognitive symptoms and overt aggression are significant predictors of suicidal ideation, with cognitive symptoms playing a mediating role. These findings suggest potential targets for therapeutic intervention.

The study aimed to investigate the alterations in spontaneous brain activity, as measured by fractional amplitude of low-frequency fluctuation (fALFF), in adolescents with high-functioning autism spectrum disorder (HFASD) and to explore the relationship between these alterations and the severity of autistic symptoms. We recruited 58 adolescents with HFASD and 66 typically developing (TD) controls, matched for age, gender, and full-scale intelligence quotient (FSIQ). Group-level analysis was conducted to identify variances in fALFF between individuals with autism spectrum disorder (ASD) and TD controls. The assessment of symptom severity in individuals with ASD was conducted utilizing the Autism Behavior Checklist (ABC). A voxel-wise correlation analysis was performed to investigate the relationships between symptom severity and the fALFF mapping in individuals with ASD, specifically in cerebral regions exhibiting ReHo abnormalities. Compared to TD controls, adolescents with HFASD showed reduced fALFF in several brain regions, including the bilateral inferior parietal lobule (IPL), right precuneus, right postcentral gyrus, bilateral middle temporal gyrus, and left cingulate gyrus. Positive correlations were observed between fALFF values in the left IPL and the Relating, Sensory, and total scores of the Autism Behavior Checklist (ABC) scale, while fALFF values in the left postcentral gyrus showed positive correlations with the Social self-help scores. These findings suggest that modifications in local spontaneous brain activity within these regions may be associated with the symptomatology of ASD, potentially enhancing our understanding of the neural mechanisms underlying the symptoms of ASD and facilitating earlier identification and improved treatment strategies.

Objective This study investigates the efficacy of an InterRhythmic Care (IRC) for major depressive disorder (MDD). There is a lack of clinical studies on its effect on depression. Methods In this eight-week, randomized, single-blind, controlled trial, 120 patients with MDD were randomly assigned to receive IRC or Internet general psychoeducation (IGP). Participants’ depressive and anxiety symptoms, interpersonal relationships, social function, and biological rhythms were assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Scale (HAMA), Interpersonal Comprehensive Diagnostic Scale (ICDS), Sheehan Disability Scale (SDS), and Morning and Evening Questionnaire (MEQ) at baseline and the 8th week. Results Compared to participants in IGP, participants in IRC had lower HAMD total scores, anxiety/somatization, weight, cognitive disturbance, retardation, and sleep disturbance subscores in patients with MDD (F = 190.94, p Bonferroni < 0.001; F = 83.13, p Bonferroni < 0.001; F = 4.15, p Bonferroni = 0.048; F = 65.42, p Bonferroni < 0.001; F = 53.15, p Bonferroni < 0.001; F = 67.76, p Bonferroni < 0.001, respectively);HAMA total score, somatic anxiety subscore, psychogenic anxiety subscore (F = 142.97, p Bonferroni < 0.001; F = 111.06, p Bonferroni < 0.001; F = 128.04, p Bonferroni < 0.001); ICDS total score and subscores for conversation, making friends, manners; and SDS subscores for work/school, social life, family life, and days underproductive (F = 17.38, p Bonferroni <0.001; F = 14.61, p Bonferroni < 0.001; F = 10.97, p Bonferroni = 0.001; F = 11.74, p Bonferroni = 0.001; F = 4.85, p Bonferroni = 0.031; F = 16.29, p Bonferroni < 0.001; F = 12.11, p Bonferroni = 0.001; F = 8.3, p Bonferroni = 0.005) at the end of the intervention period. Conclusions IRC helped patients with MDD improve clinical symptoms, including depressive and anxiety symptoms, interpersonal problems, and social function.

The characteristic features of dissociative conversion disorder entail a partial or complete loss of normal integration in memory, identity awareness, immediate sensation, and motor control. This article documents a case of the disorder presenting with an onset of depressive mood, diminished interest, and facial tics, subsequently accompanied by intermittent fainting spells with limb convulsions. Despite multiple consultations in both general hospitals and psychiatric settings, and despite treatment with various antidepressants and antiepileptic medications, the patient's symptoms showed no significant improvement. The report of this case deepens the understanding of a complex and commonly misdiagnosed condition, offering valuable insights for the diagnosis and treatment of patients exhibiting similar symptoms.

Major depressive disorder (MDD) is a common mental illness. Currently, nearly 16% of the global population is affected by depression-related symptoms, while the diagnosis and treatment rate of MDD patients in China is only 9.5%. MDD is characterised by high morbidity and low recovery rate, and how to effectively improve its therapeutic effect has been a hot research topic in recent years. Antidepressants, as the main treatment for MDD, have the disadvantages of many adverse effects and slow onset of action, prompting people to pay attention to the non-pharmacological treatments of MDD. Dietary intervention is a kind of non-pharmacological treatment by changing dietary structures and rhythms; the current application of dietary intervention to psychiatry is very extensive, and it has been proved to be effective in the treatment of depression. Recent research suggests that dietary interventions can treat and ameliorate depressive symptoms by influencing brain-gut axis-related eating mechanisms. This article reviews the multidimensional exploration of dietary interventions in the treatment of depression: dietary structure interventions, dietary rhythm interventions, and the role of intestinal flora. It details the modalities of dietary interventions and the related mechanisms involved, and provides reference for dietary interventions in the treatment of depression-related symptoms.

A diabetic foot ulcer (DFU) is a common and serious complication of diabetes. This complication can result in amputation and death because of the several challenges associated with wound healing that can be attributed to the complex wound microenvironment, including biofilm infection, hyperglycemia, and diabetic angiopathy. Existing investigations on the wound-healing rate consider only one or two pathogenic factors, and therefore, despite the extensive research on these pathological microenvironments, there is an urgent need to optimize the wound-healing rate in patients with diabetic foot ulcers. To this end, a multitasking asynchronous collaborative nanosystem is designed in this study. The designed nanosystem can efficiently clear biofilm infections using optimized photodynamic therapy based on a poly photosensitizer ionic liquid (i.e., Ce6IL), reduce local blood glucose concentration using glucose oxidase, and reconstruct blood vessels by stimulating endothelial cell proliferation and migration using nitric oxide. The experimental results indicate that the three-step sequential collaboration strategy for clearing biofilm infections, reducing glucose concentrations, and reconstructing damaged blood vessels can help significantly accelerate wound healing rate in patients with diabetic foot ulcers.

INTRODUCTION:Arsenicals have a special place in the history of human health, acting both as poison and medicine. Having been used to treat a variety of diseases in the past, the success of arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL) in the last century marked its use as a drug in modern medicine. To expand their role against cancer, there have been clinical uses of arsenicals worldwide and progress in the development of drug delivery for various malignancies, especially solid tumors. AREAS COVERED:In this review, conducted on Google Scholar [1977-2024], we start with various forms of arsenicals, highlighting the well-known ATO. The mechanism of action of arsenicals in cancer therapy is then overviewed. A summary of the research progress in developing new delivery approaches (e.g. polymers, inorganic frameworks, and biomacromolecules) in recent years is provided, addressing the challenges and opportunities in treating various malignant tumors. EXPERT OPINION:Reducing toxicity and enhancing therapeutic efficacy are guidelines for designing and developing new arsenicals and drug delivery systems. They have shown potential in the fight against cancer and emerging pathogens. New technologies and strategies can help us harness the potency of arsenicals and make better products.

Background The problem of suicide has become increasingly common in individuals with major depressive disorder (MDD). Transcranial direct current stimulation (tDCS) is an effective treatment for MDD with 2 milliamperes (mA) for at least 30 min per day for 2 weeks. This study aims to investigate the efficacy of daily duration-doubled tDCS as an adjunctive intervention for rapidly reducing suicidal ideation and improving depression in MDD patients. Methods In this double-blind, randomized, sham-controlled study, 76 MDD patients with suicidal ideation are randomly assigned to either active ( n =38) or sham ( n =38) tDCS group. The anode and cathode are placed over the scalp areas corresponding to left and right dorsolateral prefrontal cortex (DLPFC), respectively, and each stimulation lasts for 60 min. The primary outcome is defined as change of Beck Scale for Suicide Ideation (BSI) after 5 and 10 sessions. The change of other clinical assessments, blood biomarkers related to suicidal ideation and depressive sumptoms are defined as secondary outcomes. Blood biomarkers related to suicidal ideation are collected at baseline and after 10 sessions. Discussion This study suggests the adjunctive duration-doubled tDCS might be a novel method to rapidly reduce suicidal ideation and improve depressive symptom. The variation of biomarkers could be potential predictive models of suicide risk. Trial registration The trial protocol is registered with ClinicalTrials.gov under protocol registration number NCT05555927. Registered on September 25, 2022.

Radiotherapy has long been recognized as an effective conventional approach in both clinical and scientific research, primarily through mechanisms involving DNA destruction or the generation of reactive oxygen species to target tumors. However, significant challenges persist, including the unavoidable damage to normal tissues and the development of radiation resistance. As a result, nanotechnology-based radiotherapy has garnered considerable attention for its potential to enhance precision in irradiation, improve radiosensitization, and achieve therapeutic advancements. Importantly, radiotherapy alone frequently falls short of fully eradicating tumors. Consequently, to augment the efficacy of radiotherapy, it is often integrated with other therapeutic strategies. This review elucidates the mechanisms of radiotherapy sensitization based on diverse nanoparticles. Typically, radiotherapy is sensitized through augmenting reactive oxygen species production, targeted radiotherapy, hypoxia relief, enhancement of antitumor immune microenvironment, and G2/M cell cycle arrest. Moreover, the incorporation of nanoparticle-based anti-tumor strategies with radiotherapy markedly enhances the current state of radiotherapy. Additionally, a compilation of clinical trials utilizing nano-radioenhancers is presented. Finally, future prospects for clinical translation in this field are thoroughly examined.

Background: Anhedonia, the core symptom of major depressive disorder (MDD), is highly prevalent in patients with depression. Anhedonia is associated with low efficacy of drug treatment, high suicide rates, and poor social function. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technology that uses constant, low-intensity direct current to treat MDD by regulating cortical activity and neuronal excitability. However, little is known about the efficacy of tDCS for treating anhedonia in patients with depression, and even the existing results of clinical trials are conflicting. In addition, there is no consensus on what brain regions should be targeted by tDCS during the treatment of anhedonia in patients with depression. Objective: This study aimed to evaluate the efficacy and safety of tDCS over the left dorsolateral prefrontal cortex (DLPFC) and right orbitofrontal cortex (OFC) in the improvement of anhedonia in patients with depression and finally identified suitable brain regions to be stimulated during treatment. Methods: This randomized, double-blind, sham-controlled clinical trial recruited 70 patients with anhedonia and depressive episodes. Patients were randomly assigned to three groups according to the stimulation site: right orbitofrontal cortex (OFC), left dorsolateral prefrontal cortex (DLPFC), and sham stimulation. Each group received twelve 20-min interventions (ten as primary treatment and two for consolidation). The primary outcome was a decrease in Snaith-Hamilton Pleasure Scale (SHAPS) scores after primary treatment. Evaluations were performed at baseline, post-treatment, and 8-week follow-up. Results: The depression mood of the three groups of patients at each time point was better than the baseline, but there was no significant difference in the efficacy between the groups (p>0.05). On the basis of the improvement of depression, this study found that tDCS of the DLPFC significantly improved anhedonia (p = 0.028) after primary treatment (2 weeks), and tDCS of the DLPFC and OFC significantly improved social functioning (p = 0.005) at 8-week follow-up. Limitations: The sample size of this study was small, with only about 23/24 patients in each group completing the intervention assessments; due to the impact of the COVID-19 epidemic, data analysis was limited by the lack of patients during the follow-up period. Conclusions: tDCS of the DLPFC significantly improves anhedonia in depressed patients and is thus a potential adjuvant therapy for anhedonia in these patients.

Background:Depression, anxiety and schizophrenia among older persons have become global public health challenges. However, the burden of these disorders in ageing and aged countries has not been analysed. Aims:To investigate the burden of depression, anxiety and schizophrenia among older adults in ageing and aged countries. Methods:Using data from the Global Burden of Disease Study 2019, we calculated the estimated annual percentage change (EAPC) in the age-standardised incidence rates (ASIR) and age-standardised disability-adjusted life years (DALYs) rates (ASDR) for depression, anxiety and schizophrenia of older people in ageing countries (China, India, Indonesia) and aged countries (Japan, Italy, Portugal) between 1990 and 2019. Trends in incidence and DALYs were analysed by gender and age. Results:In 2019, the highest incidence of depression, anxiety and schizophrenia in the older population in aged countries was in Japan (927 271.3 (752 552.3-1 125 796.5), 51 498.2 (37 625.7-70 487.3) and 126.0 (61.0-223.2), respectively), while the highest incidence in ageing countries was in China (5 797 556.9 (4 599 403.4-7 133 006.5), 330 256.1 (246 448.9-445 987.4) and 1067.7 (556.2-1775.9), respectively). DALYs for these disorders were similar, with the highest in Japan and China. From 1990 to 2019, the ASIR for depressive disorders decreased in aged countries but increased in ageing countries; the ASIR for anxiety disorders and schizophrenia declined in both ageing and aged countries. The ASDR for depressive disorders was consistent with the ASIR but not for anxiety disorders and schizophrenia. The ASIR for depressive disorders was higher in older women, while the opposite was observed in anxiety disorders and schizophrenia. Notably, the conditions of burden of depressive disorders, anxiety disorders and schizophrenia in the 65-70-year-old age group were the most burdensome. Conclusions:The incidence and DALYs of these three mental disorders increased while exhibiting differences between ageing and aged countries. Raising awareness about formulating health policies for preventing and treating mental disorders in the older population is necessary to reduce the future burden posed by the ageing challenge.