A Platinum-Aluminum Bimetallic Salen Complex for Pro-senescence Cancer Therapy.

Cell senescence is defined as irreversible cell cycle arrest, which can be triggered by telomere shortening or by various types of genotoxic stress. Induction of senescence is emerging as a new strategy for the treatment of cancer, especially when sequentially combined with a second senolytic drug capable of killing the resulting senescent cells, however severely suffering from the undesired off-target side effects from the senolytic drugs. Here, we prepare a bimetalic platinum-aluminum salen complex (Alumiplatin) for cancer therapy-a combination of pro-senesence chemotherapy with in situ senotherapy to avoid the side effects. The aluminum salen moiety, as a G-quadruplex stabilizer, enhances the salen's ability to induce cancer cell senescence and this phenotype is in turn sensitive to the cytotoxic activity of the monofunctional platinum moiety. It exhibits an excellent capability for inducing senescence, a potent cytotoxic activity against cancer cells both in vitro and in vivo, and an improved safety profile compared to cisplatin. Therefore, Alumiplatin may be a good candidate to be further developed into safe and effective anticancer agents. This novel combination of cell senescence inducers with genotoxic drugs revolutionizes the therapy options of designing multi-targeting anticancer agents to improve the efficacy of anticancer therapies.

Cu2+-Dominated Chirality Transfer from Chiral Molecules to Concave Chiral Au Nanoparticles.

Foreign ions as additives are of great significance for realizing excellent control over the morphology of noble metal nanostructures in the state-of-the-art seed-mediated growth method; however, they remain largely unexplored in chiral synthesis. Here, we report on a Cu2+-dominated chiral growth strategy that can direct the growth of concave chiral Au nanoparticles with C3-dominant chiral centers. The introduction of trace amounts of Cu2+ ions in the seed-mediated chiral growth process is found to dominate the chirality transfer from chiral molecules to chiral nanoparticles, leading to the formation of chiral nanoparticles with a concave VC geometry. Both experimental and theoretical results further demonstrate the correlation between the nanoparticle structure and optical chirality for the concave chiral nanoparticle. The Cu2+ ion is found to dominate the chiral growth by selectively activating the deposition of Au atoms along the [110] and [111] directions, facilitating the formation of the concave VC. We further demonstrate that the Cu2+-dominated chiral growth strategy can be employed to generate a variety of concave chiral nanoparticles with enriched geometric chirality and desired chiroptical properties. Concave chiral nanoparticles also exhibit appealing catalytic activity and selectivity toward electrocatalytic oxidation of enantiomers in comparison to helicoidal nanoparticles. The ability to tune the geometric chirality in a controlled manner by simply manipulating the Cu2+ ions as additives opens up a promising strategy for creating chiral nanomaterials with increasing architectural diversity for chirality-dependent optical and catalytic applications.

Left ventricular reverse remodelling as a promising strategy for resolving left ventricular thrombus.

AIMS: Recent years, several studies have suggested that abnormal baseline left ventricular (LV) function and structure are associated with left ventricular thrombus (LVT) formation. Despite this, most studies have given less attention to the potential role of left ventricular reverse remodelling (LVRR), that is, the improvement of LV function and structure, in resolving LVT. In this study, we aim to investigate the clinical characteristics, prognosis, and LVT resolution in patients with LVRR. METHODS AND RESULTS: This is a retrospective study conducted at The First Affiliated Hospital of Dalian Medical University. Our cohort consists of patients diagnosed with LVT between 1 November 2015 and 31 May 2020. Enrolled patients were categorized into two groups: LVRR and Failure of LVRR. The primary endpoints included LVT resolution and embolic events. A total of 84 patients were included in the study, with 59 patients in the LVRR group and 25 patients in the Failure of LVRR group. In our study, patients in the LVRR group experienced higher incidence of LVT resolution and a lower risk of embolic events. Multivariate logistic analysis revealed that Failure of LVRR was the only independent negative predictor for LVT resolution and positive predictor for embolic events. CONCLUSIONS: Patients with LVRR experience higher incidence of LVT resolution and have lower risk of embolic events, highlighting the significance of identifying and mitigating risk factors that contribute to abnormal LV function and structure in management of patients with LVT.

Effects of mini-basketball training program on social communication impairments and regional homogeneity of brain functions in preschool children with autism spectrum disorder.

BACKGROUND: Social communication impairments (SCI) is a core symptom of autism spectrum disorder (ASD) and is marked by challenges in social interaction. Although physical exercise has been shown to improve SCI, this finding has not been supported by comprehensive scientific evidence. Existing research has established a strong link between the SCI in children with ASD and abnormalities in regional homogeneity (ReHo). Therefore, investigating the effects of physical exercise on SCI and Reho in patients with ASD may help to elucidate the neurological mechanisms involved. METHODS: The present study included 30 preschool children diagnosed with ASD, with 15 participants in each group (experimental and control). The experimental group underwent a 12-week mini-basketball training program (MBTP) based on routine behavioral rehabilitation, while the control group only received routine behavioral rehabilitation. The Social Responsiveness Scale-Second Edition (SRS-2) was employed to assess SCI in both groups. Resting-state functional magnetic resonance imaging technology was used to evaluate ReHo in both groups. RESULTS: After 12-week of MBTP, significant group × time interactions were observed between the experimental and control groups in total SRS-2 scores (F = 14.514, p < 0.001, ηp2 = 0.341), as well as in the domains of social cognition (F = 15.620, p < 0.001, ηp2 = 0.358), social communication (F = 12.460, p < 0.01, ηp2 = 0.308), and autistic mannerisms (F = 9.970, p < 0.01, ηp2 = 0.263). No statistical difference was found in the scores for the social awareness subscale and social motivation subscale in the group × time interaction (all p > 0.05). The experimental group exhibited increased ReHo in the right Cerebellum_Crus1 and right parahippocampal gyrus, coupled with decreased ReHo in the left middle frontal gyrus (orbital part), left superior frontal gyrus (dorsolateral), left postcentral gyrus, and right superior parietal gyrus. Furthermore, a decrease in ReHo in the left postcentral gyrus positively correlated with changes in social communication scores in SCI behaviors (p < 0.05). CONCLUSIONS: Our study underscores the effectiveness of a 12-week MBTP in ameliorating SCI and abnormalities in ReHo among preschool children with ASD. TRIAL REGISTRATION: The trial is retrospectively registered on the Chinese Clinical Trial Registry (ChiCTR1900024973; August 5, 2019).

Highly Active CoNi-CoN3 Composite Sites Synergistically Accelerate Oxygen Electrode Reactions in Rechargeable Zinc-Air Batteries.

Reaching rapid reaction kinetics of oxygen reduction (ORR) and oxygen evolution reactions (OER) is critical for realizing efficient rechargeable zinc-air batteries (ZABs). Herein, a novel CoNi-CoN3 composite site containing CoNi alloyed nanoparticles and CoN3 moieties is first constructed in N-doped carbon nanosheet matrix (CoNi-CoN3 /C). Benefiting from the high electroactivity of CoNi-CoN3 composite sites and large surface area, CoNi-CoN3 /C shows a superior half-wave potential (0.88 V versus RHE) for ORR and a small overpotential (360 mV) for OER at 10 mA cm-2 . Theoretical calculations have demonstrated that the introduction of CoNi alloys has modulated the electronic distributions near the CoN3 moiety, inducing the d-band center of CoNi-CoN3 composite site to shift down, thus stabilizing the valence state of Co active sites and balancing the adsorption of OER/ORR intermediates. Accordingly, the reaction energy trends exhibit optimized overpotentials for OER/ORR, leading to superior battery performances. For aqueous and flexible quasi-solid-state rechargeable ZABs with CoNi-CoN3 /C as catalyst, a large power density (250 mW cm-2 ) and high specific capacity (804 mAh g-1 ) are achieved. The in-depth understanding of the electroactivity enhancement mechanism of interactive metal nanoparticles and metal coordinated with nitrogen (MNx ) moieties is crucial for designing novel high-performance metal/nitrogen-doped carbon (M─N─C) catalysts.

Migraine Duration as a Potential Amplifier of Obesity.

Purpose: Migraine is a complex neurovascular disorder with obesity as a notable risk factor. This study aimed to investigate an under-researched area of the association between migraine duration and body composition. Patients and Methods: Patients with migraine from a neurology outpatient department were enrolled and were categorized into four groups based on illness duration: 1 year, 1-5 years, 5-10 years, and >10 years. Patient demographics, blood biochemistry, and body composition data were collected and analyzed statistically. Results: Patients with migraine were predominantly female, with lower education levels, significant work stress, poor sleep, and limited exercise. Longer migraine duration corresponded to increased obesity metrics. Notably, those patients with under 1 year of illness showed elevated blood lipid and liver function levels, whereas those with >10 years showed increased weight, waist circumference, body mass index, and fat content, despite higher physical activity. Significant positive correlation between obesity metrics and migraine duration was seen in patients who had migraine for >1 year. Conclusion: Our findings indicate that protracted episodes of migraine could amplify obesity tendencies, underscoring the imperative of weight regulation in migraine intervention to diminish ensuing adiposity-associated hazards.

Association between adult attachment and mental health states among health care workers: the mediating role of social support.

Background: To determine the relationships between attachment style, social support, and mental health states, as well as the mediation mechanism within this relationship, we conducted a survey among healthcare workers during the coronavirus disease 2019 (COVID-19) epidemic quarantine. Methods: The survey assessed their mental health states, adult attachment style, social support, and some other relevant information. Mental health states were represented by the overall state of sleep, physical and emotional assessment. A multiple mediator model was used to explain how social support could mediate the relationship between attachment and mental health states during COVID-19 quarantine. Results: Our findings revealed that 33.3% of the participants experienced emotional issues, 8.5% had sleep problems, and 24.9% reported physical discomfort. The direct effect of adult attachment styles on mental health states during COVID-19 quarantine was significant (c' = -0.3172; p < 0.01). The total indirect effect also showed statistical significance (ab = -0.1857; p < 0.01). Moreover, the total effect of adult attachment styles on mental health states was -0.5029 (c = -0.5029; p < 0.01). Subjective social support and utilization of social support play mediating roles in the relationship between attachment style and mental health states, respectively (ab1 = -0.1287, 95% CI: -0.9120 to -0.3341, ab2 = 0.0570, 95% CI: -0.4635 to -0.1132). Conclusion: These findings highlight social support played a mediation role between attachment style and mental health states. Thus, offering social support during a crisis might be useful for those individuals with an insecure attachment.

Effectiveness of diabetes shared care program on metabolic indicators of people with type 2 diabetes: A systematic review and meta-analysis.

AIMS: To explore the effectiveness of the Taiwanese Diabetes Shared Care Program (DSCP) on improving the metabolic indicators of people with type 2 diabetes. METHODS: Relevant studies published between January 2002 and August 2021 were retrieved from Chinese- and English-language electronic databases, including PubMed, MEDLINE, CINAHL, ProQuest, Cochrane Library, Airiti Library, and Taiwan Periodical Literature System. After screening, studies that met inclusion criteria were included in the literature review. RevMan 5.4 was employed for a meta-analysis. RESULTS: Ten studies published between 2007 and 2021 were included in the systematic review, with nine of them contributing to the meta-analysis. In total, 1506 and 1388 participants were classified into DSCP and non-DSCP groups, respectively, for the meta-analysis. The results revealed that the DSCP significantly improved glycated hemoglobin levels (mean difference [MD]: -0.50, 95% Confidence Interval [CI]: -0.83 to -0.17) and body weights (MD: -0.83, 95% CI: -1.29 to -0.38) within 1-year follow-up. However, it did not show significant improvement in other metabolic indicators. CONCLUSIONS: Taiwanese DSCP led to improvements in glycated hemoglobin levels and body weights among people with type 2 diabetes. This study suggests that people with diabetes and health-care institutions should consider participating in the DSCP.

Foxp2 Is Required for Nucleus Accumbens-mediated Multifaceted Limbic Function.

The forkhead box protein P2 (Foxp2), initially identified for its role in speech and language development, plays an important role in neural development. Previous studies investigated the function of the Foxp2 gene by deleting or mutating Foxp2 from developmental stages. Little is known about its physiological function in adult brains. Although Foxp2 has been well studied in the dorsal striatum, its function in the nucleus accumbens (NAc) of the ventral striatum remains elusive. Here, we examine the physiological function of Foxp2 in NAc of mouse brains. We conditionally knocked out Foxp2 by microinjections of AAV-EGFP-Cre viruses into the medial shell of NAc of Foxp2 floxed (cKO) mice. Immunostaining showed increased c-Fos positive cells in cKO NAc at basal levels, suggesting an abnormality in Foxp2-deficient NAc cells. Unbiased behavioral profiling of Foxp2 cKO mice showed abnormalities in limbic-associated function. Foxp2 cKO mice exhibited abnormal social novelty without preference for interaction with strangers and familiar mice. In appetitive reward learning, Foxp2 cKO mice failed to learn the time expectancy of food delivery. In fear learning, Foxp2 cKO mice exhibited abnormal increases in freezing levels in response to tone paired with foot shock during fear conditioning. The extinction of the fear response was also altered in Foxp2 cKO mice. In contrast, conditional knockout of Foxp2 in NAc did not affect locomotion, motor coordination, thermal pain sensation, anxiety- and depression-like behaviors. Collectively, our study suggests that Foxp2 has a multifaceted physiological role in NAc in the regulation of limbic function in the adult brain.

Examining the molecular mechanisms of topiramate in alleviating insulin resistance: A study on C2C12 myocytes and 3T3L-1 adipocytes.

PURPOSE: Migraine, a severely debilitating condition, may be effectively managed with topiramate, known for its migraine prevention and weight loss properties due to changes in body muscle and fat composition and improved insulin sensitivity. However, the mechanism of topiramate in modulating insulin response in adipocytes and myocytes remains elusive. This study aims to elucidate these molecular mechanisms, offering insights into its role in weight management for migraine sufferers and underpinning its clinical application. METHODS: Insulin resistance improvements were evaluated through glucose uptake measurements in C2C12 muscle cells and 3T3L-1 adipocytes, with Oil red O staining conducted on adipocytes. RNA-seq transcriptome analysis was used to identify the regulatory target genes of topiramate in these cells. The involvement of key genes and pathways was further validated through western blot analysis. RESULTS: Topiramate effectively reduced insulin resistance in C2C12 and 3T3L-1 cells. In C2C12 cells, it significantly lowered SORBS1 gene and protein levels. In 3T3L-1 cells, topiramate upregulated CTGF and downregulated MAPK8 and KPNA1 genes. Changes were notable in nuclear cytoplasmic transport and circadian signaling pathways. Furthermore, it caused downregulation of MKK7, pJNK1/ JNK1, BMAL1, and CLOCK proteins compared to the insulin-resistant model. CONCLUSION: This study provides preliminary insights into the mechanisms through which topiramate modulates insulin resistance in C2C12 myocytes and 3T3L-1 adipocytes, enhancing our understanding of its therapeutic potential in managing weight and insulin sensitivity in migraine patients.

Neutral nickel-catalyzed dehydrosulfonylation of unactivated allylic alcohols under mild conditions.

Allyl sulfones are important sulfur-containing compounds that have widespread applications in organic synthesis, medicinal chemistry and materials science. Herein, nickel-catalysed dehydrosulfonylation of unactivated allyl alcohols with aryl sulfonyl hydrazides without additional active agents under mild conditions was developed. A variety of functional allyl sulfones could be efficiently synthesized in the presence of air-stable Ni(acac)2 as the catalyst and 1,1'-bis(diphenylphosphino)ferrocene (DPPF) as the ligand.

Bone metastasis is a late-onset and unfavorable event in survivors of gastric cancer after radical gastrectomy: Results from a clinical observational cohort.

Background: The timing and incidence of recurrent bone metastasis (BM) after radical gastrectomy in patients with gastric cancer (GC) as well as the survival of these patients were not fully understood. The aim of this study was to analyze the data of an observational GC cohort and identify patients who underwent curative gastrectomy and had recurrent BM to describe and clarify the pattern and profile of BM evolution after surgery. Methods: Data were retrieved from a hospital-based GC cohort, and patients who underwent upfront radical gastrectomy were selected. The time points of specific organ metastatic events were recorded, and the person-year incidence rate of metastatic events was calculated. The latency period of BM events after gastrectomy was measured and compared with that of the other two most common metastatic events, liver metastasis (LM) and distant lymph node metastasis (LNM), using analysis of variance. Propensity score matching and subgroup analysis were used for sensitivity analysis. Results: A total of 1324 GC cases underwent radical gastrectomy between January 2011 and December 2021. Of these, 67 BM, 218 LM, and 248 LNM occurred before the last follow-up. The incidence of BM events was 1.7/100 person-years, which was approximately 3-fold lower than that of LM and distant LNM events (5.5 and 6.3 per 100 person-years, respectively). BM events had a significantly longer latency (median time, 16.5 months) than LM and LNM events (11.1 and 12.0 months, respectively). Recurrent BM led to a worse prognosis (median survival, 4.5 months) than those of LM and LNM events (median survival, 7.7 and 7.1 months, respectively). However, no difference in overall survival after gastrectomy was observed among the groups. Conclusions: Compared with other common metastatic events, BM in GC after gastrectomy is a late-onset event indicating poor survival. Trial registration: No. ChiCTR1800019978; http://www.chictr.org.cn/.

Effect of monosaccharide composition and proportion on the bioactivity of polysaccharides: A review.

Polysaccharides have been widely used in pharmaceutical and food industries due to their diverse bioactivity, high safety, and few or no side effects. However, inability to quickly produce, screen, and synthesize bioactive polysaccharides is the limiting factor for their development and application. Structural features determine and influence the bioactivity of polysaccharides. Among them, monosaccharide is the basic unit of polysaccharide, which not only affects electrification, functional group, and bioactivity of polysaccharide but also is one of the simplest polysaccharide indexes to be detected. At present, effects of monosaccharide composition and proportion on anti-inflammatory, antioxidant, antitumor, immunomodulatory, antibacterial, and prebiotic activities of polysaccharides are reviewed. Further problems need to be considered during regulation and analysis of monosaccharide composition and proportion of polysaccharides. Overall, present work will provide help and reference for production, development, and structure-function investigation of polysaccharides based on their monosaccharide.

Dealuminated Beta zeolite reverses Ostwald ripening for durable copper nanoparticle catalysts.

Copper nanoparticle-based catalysts have been extensively applied in industry, but the nanoparticles tend to sinter into larger ones in the chemical atmospheres, which is detrimental to catalyst performance. In this work, we used dealuminated Beta zeolite to support copper nanoparticles (Cu/Beta-deAl) and showed that these particles become smaller in methanol vapor at 200°C, decreasing from ~5.6 to ~2.4 nanometers in diameter, which is opposite to the general sintering phenomenon. A reverse ripening process was discovered, whereby migratable copper sites activated by methanol were trapped by silanol nests and the copper species in the nests acted as new nucleation sites for the formation of small nanoparticles. This feature reversed the general sintering channel, resulting in robust catalysts for dimethyl oxalate hydrogenation performed with supported copper nanoparticles for use in industry.

Self-assembled hole-transporting material constructed by chlorination and conjugation strategies toward efficient organic solar cells.

The moderate charge-transporting capability together with higher-lying energetic levels of self-assembling hole-transporting materials (SAMs) constrain the productive carrier extraction dynamics. To alleviate this issue, a synergetic chlorination and extended conjugation strategy is applied to explore a novel HTL, named 2Cl-TPA-CN-COOH. Indeed, the chlorinated head backbone would deepen the energetic level and strengthen the intramolecular push-pull effect, whereas the elongated conjugation unit would boost the carrier-transporting potential. Consequently, a champion power conversion efficiency (PCE) of 18.6% with upgraded stability is obtained in a 2Cl-TPA-CN-COOH cell. These results demonstrate a new insight of the molecular configuration of SAMs, which would contribute to the enhancements of performance and reliability in the OSC field.

Interfacial Coupling Engineering Boosting Electrocatalytic Performance of CoFe Layered Double Hydroxide Assembled on N-Doped Porous Carbon Nanosheets for Water Splitting and Flexible Zinc-Air Batteries.

The disadvantages of layered double hydroxides (LDHs) such as easy stacking, poor inherent conductivity, and limited versatility hinder their application in splitting water and zinc-air batteries (ZABs). Interface engineering to regulate the electron distribution of LDHs by introducing another component is a way to compensate for the poor electron transport capacity of LDHs during catalysis. Herein, a hierarchical structure is synthesized by assembling CoFe-LDH nanosheets onto the surface of layered N-doped porous carbon (NPC), CoFe-LDH@NPC, by using an interface engineering strategy. CoFe-LDH@NPC has high catalytic activity for the oxygen/hydrogen evolution reaction (OER/HER) with overpotentials of 280/100 mV, respectively. The two-electrode water splitting catalyzed by CoFe-LDH@NPC only needs 1.61 V to drive a current density of 10 mA cm-2 for 60 h. The theoretical results show that there is an electron-deficient/electron-rich interface between the NPC substrate and the CoFe-LDH in CoFe-LDH@NPC. The electrons on the coupling interface are easily transferred, which results in a change of the adsorption behavior of the reaction intermediates and improves the catalytic activity for the OER and HER. In addition, CoFe-LDH@NPC-catalyzed rechargeable flexible ZABs have excellent performance with low charge-discharge polarization (0.87 V) and a long-term stability of 65 h.

Prediction and potential risk factors for electronic cigarette use behaviors among adolescents: a pilot study in Chiayi, Taiwan.

Introduction: Electronic cigarette (e-cigarette) use among adolescents has become increasingly common; therefore, effectively reducing adolescent e-cigarette use is an urgent issue. We aimed to predict and identify potential factors related to adolescent e-cigarette use behaviors. Methods: This cross-sectional study was conducted using anonymous questionnaires given to Taiwanese high school students in 2020. Approximately 1,289 adolescent students completed questions on e-cigarette use, personal characteristics, family environment, and substances used. We performed multivariate logistic regression analyses to assess the model's predictive performance in terms of the area under the receiver operating characteristic curve. Results: We found that 9.3% of adolescent students used e-cigarettes. Tobacco smoking, close friends' reactions to e-cigarette use, and the use of other substances were independent risk factors for adolescent e-cigarette use. Furthermore, relative to tobacco nonuse, tobacco use and tobacco smoking dependence had odds ratios of 76.49 and 113.81, respectively. The predictive accuracy of adolescent e-cigarette use from personal characteristics, family environment, and substance use status was 73.13, 75.91, and 93.80%, respectively. Conclusion: The present study highlights the need for early prevention of e-cigarette use among adolescents, particularly those with a history of using tobacco and other substances and those who have close friends with positive attitudes towards e-cigarette use.

Unravelling the pseudocapacitive origin of graphene oxide-based aerogels by comparative insights.

We reveal the intrinsic pseudocapacitive center of graphene-oxide-based aerogels by investigating different modified graphene skeletons from various approaches. A high proportion of carbonyl groups in carbon networks is shown to optimize the construction of rational pseudocapacitive sites by triggering reversible proton-induced surface reactions, leading to satisfactory electrochemical performance.

Effects of sports intervention on aggression in children and adolescents: a systematic review and meta-analysis.

Objective: To explore the impact of sports on aggression in children and adolescents and analyze whether different conditions in the intervention, such as type of sports, or intervention duration, have different influences on the effect of interventions. Method: The study protocol was registered in PROSPERO (CRD42022361024). We performed a systematic search of Pubmed, Web of Science, Cochrane library, Embase and Scopus databases from database inception to 12 October 2022 for all studies written in English. Studies were included if they met the following PICO criteria. All analyses were carried out using the Review Manager 5.3 Software. We summarized aggression, hostility and anger scores using SMDs. Summary estimates with 95% confidence intervals were pooled using DerSimonian-Laird random effects model or fixed effects model according to between-study heterogeneity. Results: A total of 15 studies were deemed eligible for inclusion in this review. The overall mean effect size indicated that sport interventions was associated with lower aggression (SMD = -0.37, 95% CI [-0.69 to -0.06], P = 0.020; I2 = 88%). Subgroup analyses showed that non-contact sports were associated with lower aggression (SMD = -0.65, 95% CI [-1.17 to -0.13], P = 0.020; I2 = 92%) but high-contact sports were not (SMD = -0.15, 95% CI [-0.55 to 0.25], P = 0.470; I2 = 79%). In addition, when intervention duration <6 months, sport interventions was associated with lower aggression (SMD = -0.99, 95% CI [-1.73 to -0.26], P = 0.008; I2 = 90%) and when intervention duration ≥ 6 months, sport interventions was not associated with lower aggression (SMD = -0.08, 95% CI [-0.44 to -0.28], P = 0.660; I2 = 87%). Conclusion: This review confirmed that sports intervention can reduce the aggression of children and adolescents. We suggested that schools can organize young people to participate in low-level, non-contact sports to reduce the occurrence of bullying, violence and other aggression-related adverse events. Additional studies are needed to determine which other variables are associated with aggression in children and adolescents, in order to develop a more detailed and comprehensive intervention programme to reduce their aggression.

Differential Development of Dendritic Spines in Striatal Projection Neurons of Direct and Indirect Pathways in the Caudoputamen and Nucleus Accumbens.

Synaptic modification in postnatal development is essential for the maturation of neural networks. Developmental maturation of excitatory synapses occurs at the loci of dendritic spines that are dynamically regulated by growth and pruning. Striatal spiny projection neurons (SPNs) receive excitatory input from the cerebral cortex and thalamus. SPNs of the striatonigral direct pathway (dSPNs) and SPNs of the striatopallidal indirect pathway (iSPNs) have different developmental roots and functions. The spatial and temporal dynamics of dendritic spine maturation of these two types of SPNs remain elusive. Here, we delineate the developmental trajectories of dendritic spines of dSPNs and iSPNs in the caudoputamen and nucleus accumbens (NAc). We labeled dendritic spines of SPNs by microinjecting Cre-dependent AAV-eYFP viruses into newborn Drd1-Cre or Adora2a-Cre mice, and analyzed spinogenesis at three levels, including different SPN cell types, subregions and postnatal times. In the dorsolateral striatum, spine pruning of dSPNs and iSPNs occurred at postnatal day (P)30-P50. In the dorsomedial striatum, the spine density of both dSPNs and iSPNs reached its peak between P30 and P50, and spine pruning occurred after P30 and P50, respectively, for dSPNs and iSPNs. In the NAc shell, spines of dSPNs and iSPNs were pruned after P21-P30, but no significant pruning was observed in iSPNs of lateral NAc shell. In the NAc core, the spine density of dSPNs and iSPNs reached its peak at P21 and P30, respectively, and subsequently declined. Collectively, the developmental maturation of dendritic spines in dSPNs and iSPNs follows distinct spatiotemporal trajectories in the dorsal and ventral striatum.