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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction and repetitive behaviors, with currently limited therapeutic options. Oxidative stress is suggested as significant in ASD pathophysiology, making antioxidant strategies a promising therapeutic direction. Exercise reduces oxidative stress, alleviates ASD symptoms, and increases tetrahydrobiopterin (BH4) and brain-derived neurotrophic factor (BDNF) levels through AMP-activated protein kinase (AMPK) activation. MOTS-c, a mitochondrial-derived peptide acting through AMPK, mimics the effects of exercise but reportedly does not cross the blood-brain barrier (BBB). Considering the challenges in exercise adherence in ASD, our study hypothesizes that MOTS-c could increase circulating BH4 and BDNF, both of which are BBB-permeable, and alleviate oxidative stress and ASD symptoms. To evaluate this hypothesis, we investigated the effects of MOTS-c in the valproic acid-induced rat model of autism. Pregnant Sprague-Dawley rats received intraperitoneal 500 mg/kg valproic acid or saline on embryonic day 12. Female and male offspring were treated with 0.5 mg/kg/day MOTS-c or saline intraperitoneally from postnatal days 21 to 46. Following behavioral testing, animals were sacrificed, and histological and biochemical analyses were performed. Valproic acid exposure led to impaired sociability, repetitive behaviors, anxiety, cerebellar Purkinje cell loss, and increased oxidative stress and neuronal damage in the prefrontal cortex. These alterations were reversed by MOTS-c, except for anxiety and neocortical damage. No significant changes in plasma BH4 or BDNF levels were detected. Through its neuroprotective and antioxidant effects independent of BH4 and BDNF, MOTS-c may alleviate autism-like behaviors, suggesting its potential as a therapeutic candidate for ASD. Show less

Inter-individual responses to omega-3 and omega-6 polyunsaturated fatty acid (PUFA) interventions vary substantially, complicating standardized dietary recommendations and suggesting a role for genetic differences that influence fatty acid biosynthesis, metabolism, and downstream health effects. A PRISMA 2020-guided systematic search of PubMed, Embase, and Web of Science identified adult studies assessing nutrigenetic interactions in the context of PUFA interventions and outcomes, yielding 132 eligible studies (79 Tier 1; 53 Tier 2) that collectively indicate pathway-specific genetic control of PUFA handling. Across 38 studies (combined Show less

Moral inclusiveness-the scope of one's moral circle-has traditionally been studied as a single, global trait. This study instead applied latent profile analysis (LPA) to uncover nuanced moral inclusiveness profiles spanning nested layers of relational proximity (family, community, global citizen, and nonhuman living beings). The study looked across four validated scales-Kindness, Compassion, Global-Mindedness, and Speciesism-and further examined how these profiles relate to trauma, mental health, and spirituality. A cross-sectional sample of 763 U.S. participants completed measures assessing moral inclusiveness, mental health, lifetime and recent traumatic events, and three spiritual dimensions: general spirituality, spiritual decline, and awakened awareness. LPA revealed five distinct profiles: Ingroup Concern, Outgroup Concern, Average Overall Concern, Universal Empathy, and Lovers. The Ingroup Concern class exhibited the highest levels of psychopathology, the most recent traumatic events, and elevated spiritual decline. The Universal Empathy and Lovers classes reported low current distress, minimal spiritual decline, and significantly higher awakened awareness, suggesting they experienced adversity yet still maintained meaning and/or guidance. Lifetime trauma exposure alone did not preclude a broad moral scope of inclusion: the Ingroup Concern and Universal Empathy classes both reported substantial trauma histories but diverged in moral inclusiveness, possibly due to differences in spiritual injury and ongoing stress. These findings reveal that a more parochial or limited moral scope is associated with lifetime and recent adversity, current mental health challenges, and spiritual injury. More expansive concern for human and fellow living beings is associated with positive spiritual engagement and fewer immediate negative life events. Show less

Alzheimer's disease (AD) is marked by amyloid-β (Aβ) accumulation, tau pathology, and neuroinflammation. The β-site APP cleaving enzyme 1 (BACE1) is a key driver of Aβ production, while the NLRP3 inflammasome mediates microglial inflammatory responses. Histone deacetylase 6 (HDAC6), a cytoplasmic deacetylase, is upregulated in AD, yet its role in disease mechanisms remains unclear. Here, we show that HDAC6 promotes BACE1 protein stability through direct deacetylation of its C-terminal lysine (K501), thereby increasing Aβ production. HDAC6 also facilitated NLRP3 inflammasome activation in microglia, increasing IL-1β production in a catalytic domain-dependent manner. HDAC6 deficiency in 5xFAD mice reduced BACE1 accumulation, Aβ deposition, ASC speck formation, and IL-1β levels, accompanied by improved cognitive performance. Transcriptomic profiling further revealed downregulation of disease-associated microglial and neurotoxic astrocyte signatures alongside enrichment of synaptic pathways. These findings establish HDAC6 as a dual regulator of Aβ production and neuroinflammation, highlighting it as a promising therapeutic target in AD. Show less

(1) Background: The increasing environmental concentration of polystyrene nanoplastics (PS-NPs) may pose a risk of human exposure and health threats. Previous studies have demonstrated that exposure to PS-NPs poses a threat to neural synaptic plasticity, yet the underlying mechanisms remain unclear. (2) Methods: Hippocampal astrocytes and neurons were co-cultured, exposed to PS-NPs at concentrations of 10, 50, and 100 μg/mL, and cytotoxicity was assessed. We investigated PS-NP-induced impairment of synaptic plasticity by regulating the brain-derived neurotrophic factor (BDNF). (3) Results: Calmodulin-dependent protein kinase II (CaMKII) is a central molecular organizer of synaptic plasticity, learning, and memory, and its activity is intrinsically linked to intracellular calcium ion concentration. Our research indicates that PS-NPs may interfere with calcium ion signaling and CaMKIIα activity, thereby reducing CaMKIIα activity. This subsequently downregulates the expression of cAMP response element-binding protein (CREB), modulates BDNF expression, and impacts synaptic plasticity. (4) Conclusions: In summary, this study primarily focused on the effects of PS-NPs exposure on hippocampal synaptic plasticity. Show less

Thyroid hormones regulate lipoprotein metabolism-primarily by up-regulating the LDL receptor. Whether TSH relates to LDL-C in hypercholesterolemic children, and whether this depends on familial hypercholesterolemia (FH) status or the underlying defective gene, is uncertain. We evaluated TSH-lipid associations in prepubertal children and tested effect modification by FH status and, within FH, by gene with a pathogenic variant (LDLR vs APOB). We performed a cross-sectional study of prepubertal children referred to the Slovenian national tertiary center through the universal FH screening program or cascade screening. Eligibility required concurrent TSH and fasting lipid measurement and completed genetic testing (pathogenic/likely pathogenic variants in LDLR/APOB/PCSK9 vs polygenic hypercholesterolemia). Among 738 children, 182 (24.7%) were FH-positive (LDLR 132; APOB 50). In the pooled cohort, TSH did not correlate with age or lipids (all p ≥ 0.050). After sex stratification, TSH correlated with triglycerides only in males (ρ = 0.156; p = 0.012). In FH-positive children, TSH correlated with total cholesterol, LDL-cholesterol, and ApoB (ρ ~ 0.184-0.207; all p < 0.050), with no associations in FH-negative children. Interaction testing confirmed effect modification by FH (TSH × FH β = 0.141 mmol/L per mIU/L, p = 0.023). Within FH-positive children, a positive TSH-LDL-C slope was seen in LDLR carriers (β = 0.237, p = 0.004) but not in APOB carriers (β = -0.065, p = 0.655). TSH was positively associated with LDL-C only in FH due to LDLR variants, not in APOB carriers. These findings suggest that genetic background may shape hormonal sensitivity, and that attention to thyroid status could be particularly relevant in LDLR-FH. Show less

COG133, a peptide fragment derived from apolipoprotein E (ApoE) corresponding to residues 133-149, has demonstrated significant anti-inflammatory and neuroprotective activity. However, its precise anti-inflammatory mechanisms and its potential to ameliorate depression-like behaviors remain incompletely understood. This study investigated the effects of COG133 in mouse models of depression induced by lipopolysaccharide (LPS), chronic social defeat stress (CSDS), and corticosterone (CORT), as well as in LPS-stimulated BV-2 microglial cells. We found that COG133 treatment significantly alleviated depression-like phenotypes and suppressed hippocampal neuroinflammation by inhibiting microglial overactivation. Using RNA sequencing (RNA-seq) and biochemical validation, we identified the MKK3/6-p38-ATF2 signaling axis as a central mechanism underlying the anti-inflammatory effects of COG133. Pharmacological modulation of p38 MAPK further confirmed that this pathway is essential for COG133-mediated behavioral and cellular recovery. Together, these findings identify COG133 as a promising peptide candidate for the treatment of depression through modulation of the p38 MAPK-mediated neuroinflammation axis. Show less

Microcystin-LR (MC-LR) is the most prevalent and toxic microcystin congeners, posing a significant threat to aquatic organisms as well as humans; however, its underlying toxic mechanisms remain incompletely elucidated. In this study, the negative impacts of MC-LR and the underlying mechanisms in zebrafish larvae were investigated. The results demonstrated that MC-LR could penetrate zebrafish larvae and induce developmental toxicity, characterized by reduced heart rate, decreased body length, and smaller eye area. H&E staining revealed that MC-LR exposure significantly reduced the thickness of retinal layers. qPCR analysis showed altered expression levels of phototransduction and retinoic acid metabolism related genes (rho, gnat1, gnat2, opn1sw1, opn1lw1, opn1mw1, rdh1, rbp4, cyp26a1, and aldh1a2). These findings suggest that MC-LR may disrupt retinal structure and impair normal visual function in larvae. Behavioral analyses indicated that MC-LR exposure weakened spontaneous movements in embryos and impaired swimming ability in larvae, potentially due to significant alterations in the levels of glutamate, γ-aminobutyric acid, and brain-derived neurotrophic factor. Additionally, MC-LR exposure reduced visuomotor responses, delayed reactions to external stimuli, and disrupted circadian rhythms, which may be attributed to altered expression levels of circadian rhythm-related genes (clock1a, bmal1a, per1b, cry1a, and per2), as well as changes in melatonin and arylalkylamine N-acetyltransferase 2 levels. Overall, these findings indicate that MC-LR exposure induces developmental neurotoxicity in zebrafish, and that impaired visual function and disrupted circadian rhythm may serve as key contributing factors to MC-LR-induced behavioral abnormalities, which warrant further emphasis in future ecological and health risk assessments. Show less

Disruption of metabolic interactions between astrocytes and neurons, in particular of the lactate shuttle, may contribute to neurodevelopmental and psychiatric disorders such as autism spectrum disorder (ASD) and schizophrenia. The enzyme glycine decarboxylase (GLDC), predominantly expressed in astrocytes, degrades glycine and plays a critical role in regulating NMDA receptor function and cellular metabolism. Here, we investigated whether administration of lactate would reverse schizophrenia-like phenotypes in a mouse model for psychosis with 4 copies of the Gldc gene (4cG mice). Adult male and female 4cG and wildtype mice were subjected to acute L-lactate intraperitoneal administration one hour before behavioral testing and brain collection for biochemical assays. Y-maze spontaneous alternation test, prepulse inhibition of acoustic startle test, and the three-chamber social interaction test were performed for behavioral analysis, and Western blots for protein estimations. In 4cG mice, acute lactate administration one hour before assessment rescued short-term memory deficits, acoustic startle habituation deficits, and normalized deficits in social preference behavior. Furthermore, lactate treatment restored the expression of PGC1α, a master regulator of mitochondrial biogenesis, and brain-derived neurotrophic factor (BDNF), a protein essential for synaptic plasticity. The results suggest a role for astrocytic metabolism in modulating neuronal function, and potential molecular mechanisms underlying the reversal of behavioral phenotypes. The results indicate that exogenous lactate may reverse key pathophysiological and behavioral deficits in a mouse model for schizophrenia and that lactate supplementation may be useful as a therapeutic strategy for schizophrenia and related disorders. Show less

To investigate the effect of pterostilbene (PTE), a natural dimethyl ether analog of resveratrol with higher bioavailability, on cognitive recovery after cerebral ischemia reperfusion (IR) injury and its potential mechanisms. Mice were subjected to middle cerebral artery occlusion and assigned to Sham, IR, PTE+IR, and PTE+Zinc Protoporphyrin (ZnPP)+IR groups. Cognitive function was assessed using the Morris water maze. Cerebral infarct volume was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and neuronal apoptosis was determined via TUNEL assay. The protein levels of postsynaptic density protein 95 (PSD-95), phosphorylated cAMP response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), and histone deacetylases (HDACs) in the hippocampus were measured by western blot. PTE treatment significantly reduced cerebral infarct volume, alleviated cognitive deficits, and inhibited neuronal apoptosis in the hippocampus. At the molecular level, PTE up-regulated the expression of PSD-95, p-CREB, and BDNF, while down-regulating HDAC (1, 2, 3, 4, 7) levels. The beneficial effects of PTE were partially reversed by the HO-1 inhibitor ZnPP. PTE ameliorates cognitive impairment induced by cerebral IR injury, potentially through activating the BDNF/CREB pathway and inhibiting HDAC expression. This suggests PTE as a promising neuroprotective agent for post-stroke cognitive recovery. Show less

Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) may contribute to Alzheimer's disease (AD) pathogenesis by promoting amyloid-β (Aβ) aggregation. ASC protein is mainly composed of the N-terminal pyrin domain (PYD) and the C-terminal caspase recruitment domain (CARD). This study aims to explore the different roles of the two domains of ASC in AD. The SH-SY5Y-APP695 cells were treated with ASC neutralizing antibodies against the N-terminal domain (anti-ASC N-terminal antibodies) or C-terminal domain(anti-ASC C-terminal antibodies). The cell apoptosis and Aβ production were detected. The eight-month-old APP/PS1 mice received lateral ventricle injections of anti-ASC N-terminal antibodies or anti-ASC C-terminal antibodies. The cognitive function and AD-like pathology of APP/PS1 mice were assessed. The anti-ASC N-terminal and C-terminal antibodies attenuated apoptosis and mitochondrial damage, and reduced Aβ production by inhibiting BACE1 in vitro. Furthermore, intracerebroventricular administration of anti-ASC N-terminal and C-terminal antibodies improved cognitive impairment and reduced Aβ deposition, tau hyperphosphorylation, and neuroinflammation in the APP/PS1 mice. The anti-ASC N-terminal and C-terminal antibodies may have neuroprotective effects, which are manifested as reducing cell apoptosis, improving cognitive function, and alleviating AD-like pathology in AD mice. Immunotherapies targeting ASC are promising for treating AD. Show less

Age-related macular degeneration (AMD) and Alzheimer's disease (AD) are neurodegenerative conditions that afflict millions of elderly people around the world. AMD is a progressive retinal disorder that leads to central vision loss whereas AD primarily causes cognitive decline and behavioral changes. While each disease has distinct clinical manifestations, the accumulation of extracellular amyloid-β is a common histopathologic finding. Similarly, cerebral amyloid angiopathy (CAA), a vascular condition that can exist independent or with AD, is characterized by the accumulation of amyloid-β in cerebral blood vessels. While significant investigation of the pathophysiologic links between AMD and AD has been conducted, the underlying similarities and differences in the pathobiology of AMD and CAA has not been considered. In this review, we discuss the common pathological features of these two conditions. We then discuss the similar pathobiology that involves cholesterol metabolism, apolipoprotein E, amyloid-β, and complement mediated inflammation. At the same time, we discuss key differences in their pathobiology. This discussion sheds new perspective and insights of their pathobiology. Show less

Keratoconus (KC) is a progressive disorder of corneal thinning characterized by responses in the extracellular matrix and cellular interactions. This study used bioinformatics methods to identify key genes involved in KC development and in anoikis and endoplasmic reticulum (ER) stress. KC and control datasets from the GEO database were analyzed to identify differentially expressed genes (DEGs). These were cross-referenced with anoikis and ER stress-related genes from Genecards. Functional enrichment, immune infiltration analysis, and machine learning techniques (LASSO, Random Forest) were used to identify candidate molecular signatures, which were then validated in an animal model. We identified 46 DEGs associated with anoikis and 41 DEGs related to ER stress. Functional analysis linked them to apoptosis and IL-17 signaling. Five key molecular signatures were identified: CDKN1A, MCL1, PTGS2, PTHLH, and ANGPTL4. The expression of ANGPTL4, CDKN1A, and MCL1 was consistent in the animal model. These genes are associated with inflammatory and oxidative stress responses. Twelve potential therapeutic drugs were predicted. This study identifies five candidate molecular signatures for KC related to anoikis and ER stress, offering insights into KC pathogenesis and potential targeted therapies. Show less

Hydroxychloroquine (HCQ) is an immunomodulatory agent used in autoimmune conditions. Observational studies suggest that HCQ may lower circulating cholesterol and triglyceride levels, indicating a potential cardiovascular benefit. However, the specific changes in lipoprotein particle concentrations driving these effects have not been characterized in detail. To evaluate the effects of HCQ on circulating lipids and on lipoprotein concentration and composition. A post hoc analysis was conducted within a randomized, placebo-controlled, double-blind trial investigating the effects of HCQ on glucose metabolism in adults at risk for type 2 diabetes. Outcomes were analyzed as changes from baseline (placebo-adjusted) using mixed-effects models, with adjustments for sex, age, body mass index, and statin use. Compared with placebo, HCQ reduced total cholesterol (10.4%), low-density lipoprotein (LDL) cholesterol (12.9%), and non-high-density lipoprotein (HDL) cholesterol (15.0%). LDL particle concentration decreased by 15.1% and apolipoprotein B (ApoB) by 9.7%. HCQ had no effect on HDL cholesterol, HDL particle concentration, or apolipoproteinA1 (ApoA1). However, small HDL particle concentrations fell by 20.0%, while large HDL particle concentrations increased by 17.1%. HCQ reduced triglycerides by 27.8%, which was associated with a 20.6% reduction in triglyceride content per very low-density lipoprotein (VLDL) particle. Lipoprotein(a) levels were unaffected. HCQ changes lipoprotein concentration and composition, though the effects are distinct for each lipoprotein class. Our results suggest that HCQ lowers total cholesterol by reducing LDL particle concentration, decreases triglyceride by reducing the triglyceride content of VLDL particles, and alters the relative distribution of small vs large HDL particle concentration. These findings suggest protective benefits against atherosclerosis that warrant further investigation. Show less

During the past decade, our group has induced electroconvulsive seizures (ECS) in rodent models of early-life stress to prove clear differences in antidepressant-like efficacy mainly driven by sex and age, with females and adolescents showing diminished responses (as opposed to males and adult rodents). Moreover, we have proven a role for sex hormones in this response, since letrozole, an inhibitor of the biosynthesis of estrogens, improved the antidepressant-like efficacy of ECS in adolescent female rats. In this follow-up study, we utilized selective estrogen receptor modifiers (tamoxifen and clomiphene) to evaluate how they interact with the antidepressant-like response induced by ECS in male and female adolescent rats. Early-life stressed Sprague-Dawley rats through maternal separation were treated during adolescence with tamoxifen (1 mg/kg, 7 days) or clomiphene (10 mg/kg, 5 days) and/or with ECS (95 mA, 0.6 s, 100 Hz, 1 session/day, 5 days). Antidepressant-like responses were measured behaviorally under the stress of the forced-swim test, and through hippocampal markers (cell proliferation and neurogenic differentiation, and BDNF protein level). The main results proved that tamoxifen improved the expected antidepressant-like response of ECS in adolescent rats, as observed in the forced-swim test, while boosted hippocampal proliferation and neurogenic differentiation. Contrarily, clomiphene did not alter ECS' response at the behavioral level and even showed some negative signs on the neuroplasticity markers evaluated (decreased neurogenic differentiation and BDNF content). Therefore, when considering an estrogen receptor modifier to enhance the antidepressant-like potential of ECS in adolescence, tamoxifen emerges as a promising option due to its positive behavioral and neuroplastic effects. Show less

Snail (SNAI1), a central transcription factor driving epithelial-mesenchymal transition (EMT), is pivotal in cancer metastasis and tissue remodeling. Owing to its labile nature, Snail activity is tightly controlled by post-translational modifications that dictate its stability. Here this review summarizes how the ubiquitin-proteasome system orchestrates Snail degradation through coordinated phosphorylation and ubiquitination, mediated by diverse E3 ligases and regulated by kinases, acetyltransferases and deubiquitinases. These mechanisms dynamically adjust Snail levels in both the cytoplasm and nucleus, thereby modulating EMT outcomes. In parallel, emerging studies reveal that chaperone-mediated autophagy (CMA) provides an additional layer of regulation. Through recognition of KFERQ-like motifs, CMA selectively directs cytoplasmic Snail to lysosomes for LAMP2A-dependent degradation, functioning as a quality control system. Impairment of CMA leads to nuclear accumulation of Snail, enhancing its EMT-inducing and prometastatic potential. Together, the ubiquitin-proteasome system and CMA represent complementary, context-dependent axes that maintain Snail homeostasis. Their disruption facilitates EMT activation and metastatic progression. By integrating recent findings, this review highlights the dual degradative control of Snail and its implications for cancer biology, providing a conceptual framework for therapeutic approaches aimed at restoring degradative balance and limiting metastasis. Show less

Previous research has indicated the brain-derived neurotrophic factor (BDNF) level is lower in schizophrenia and associated with cognitive impairment. Irisin-BDNF axis may strengthen learning and memory functions. This study examined associations between BDNF, peroxisome proliferator-activated receptor-gamma (PPAR gamma) and irisin with cognitive deficits in schizophrenia. We enrolled 80 patients with schizophrenia and 80 healthy controls (HCs). The enzyme-linked immunosorbent assay (ELISA) method was used for biochemical analysis. The Stroop Test, Trail Making Test (TMT), and Verbal Fluency Test (VFT) were used for cognitive assessment. Statistical analyses included t-tests, correlations, and analysis of covariance (ANCOVA) controlling key confounders. In unadjusted analyses, patients had significantly lower BDNF and PPARγ levels than HCs (ps < 0.001). After controlling for covariates, the difference in BDNF was still significant (F = 11804.71, BDNF demonstrates the most robust association with schizophrenia and cognitive function. The association of PPARγ with schizophrenia is confounded by demographic and metabolic factors, and irisin showed a limited link only to negative symptoms. Not applicable. Show less

Programmed cell death (PCD) has been linked to asthma, chronic obstructive pulmonary disease (COPD) and lung function, but the underlying genetic determinants remain unclear. A comprehensive multi-omics analysis was conducted by integrating genome-wide association studies (GWAS) with methylation quantitative trait loci (mQTL), expression quantitative trait loci (eQTL), and protein quantitative trait loci (pQTL) data. To determine the causality between exposures and respiratory traits, Summary Data-Based Mendelian Randomization (SMR) and colocalization analyses were applied. External validation was performed using replication cohorts, along with transcriptome-wide association studies (TWAS), gene-based analysis, and tissue-specific analysis. Additionally, enrichment analysis was carried out to identify biological pathways linked to respiratory traits. To explore potential therapeutic targets, drug prediction and molecular docking analyses were employed to assess the pharmacological feasibility of candidate compounds. Through the integration of multi-omics analysis, we identified six PCD-related genes associated with respiratory traits. ERBB3, SFRP1, and FGFR1 demonstrated tier 1 evidence, linking them to COPD in never-smokers, forced expiratory volume in 1 second (FEV1), and FEV1/forced vital capacity (FVC), respectively. Additionally, HSPA1B and MAPK3 were classified as tier 2 genes, associated with non-allergic asthma risk and overall COPD risk, respectively. IDUA, categorized as a tier 3 gene, was related to overall asthma. These genes play critical roles in apoptotic signaling, mesenchymal development, and molecular binding processes, emphasizing their biological significance. Additionally, molecular docking demonstrated stable binding for candidate drugs and proteins encoded by identified genes. Our study offers critical insights into the genetic basis of asthma, COPD, and lung function by identifying six genes as potential biomarkers and therapeutic targets, contributing to the development of more effective interventions for these respiratory traits. Show less

To explore the effect of Ninety-five SPF male rats were selected and randomly divided into a sham-operation group (15 rats) and an operation group (80 rats). Using Longa's suture-occluded method and chronic unpredictable mild stress method, PSD rat models were prepared. A total of 75 successfully modeled rats were randomly divided into a model group, an acupuncture group, a paroxetine group, a dacomitinib (ErbB4 inhibitor) group, and an acupuncture+dacomitinib group, with 15 rats in each one. In the acupuncture group, acupuncture was delivered at "Baihui" (GV20), "Shenting" (GV24), and bilateral "Neiguan" (PC6) and "Taichong" (LR3); and the electric stimulation with electroacupuncture instrument was exerted at "Neiguan" (PC6) and "Taichong" (LR3) on the same side, using continuous wave, at a frequency of 2 Hz, and an intensity of 0.1 mA to 1 mA, for 30 min in each intervention. In the paroxetine group, the intragastric administration was given with paroxetine, 5 mg/kg; and in the dacomitinib group, the intragastric administration was given with dacomitinib, 7.5 mg/kg. In the acupuncture+ dacomitinib group received the same interventions as the acupuncture group and the dacomitinib group. The above intervention measures were delivered once a day for consecutive 28 days in each group. Longa's score was compared, and the behavior of rats was observed using the open field test and sucrose preference test in each group. Using ELISA method, the hippocampal levels of malonaldehyde (MDA), catalase (CAT), 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) were detected. With HE staining and Nissl staining adopted, the hippocampal neuron morphology was observed. Golgi staining was employed to observe the morphological changes of dendritic spines in the hippocampal neurons. Immunohistochemistry was used to observe the positive expression of brain-derived neurotrophic factor (BDNF) and synaptophysin (SYN1) in the hippocampal tissue, and Western blot was used to detect the protein expression of NRG1 and ErbB4 in the hippocampal tissues. Compared with the sham-operation group, the Longa's score and hippocampal MDA level in the model group increased ( Show less

Emotional and motivational aspects of teacher-student relationships are central to adolescents' psychological need satisfaction and academic development. However, few longitudinal studies examine how these relational experiences evolve during adolescence or co-occur with emotional-motivational functioning. Drawing on the Self-Determination Theory and recent models of emotion transmission in classrooms, this study aims to explore how students' emotional and motivational perceptions of teachers co-occur with psychological need satisfaction in distinct developmental profiles and to examine their transitions over time during adolescence. The sample consisted of 779 German secondary school students (57% female; aged 12-15) from high-track schools, surveyed in Grade 8 (T1) and Grade 9 (T2). Latent profile analyses (LPA) and latent transition analyses (LTA) were conducted using six indicators: socio-emotional teacher-student relationship, perceived teacher motivation (positive/negative), and satisfaction of autonomy, competence and relatedness needs. Gender and academic grades were included as covariates. Three distinct profiles emerged: (1) emotionally disconnected & controlled, (2) emotionally ambivalent & uncertainly self-determined and (3) emotionally safe & self-determined. While transitions towards the moderate profile were most common, extreme profiles remained relatively stable. Lower academic performance significantly predicted membership in less favourable profiles. Findings underscore the intertwined nature of emotional relationships and motivational experiences in adolescence. Socio-emotional teacher support emerged as a key differentiator between profiles. Interventions should target emotionally supportive climates to foster students' psychological need satisfaction and engagement. Show less

The impact of obstructive sleep apnea (OSA) on subsequent cardiovascular events in patients with acute coronary syndrome (ACS) remains debated. This study aims to investigate whether the association of OSA with cardiovascular events is affected by lipoprotein (a) [Lp(a)] levels. This is a sub-analysis of prospective cohort study (OSA-ACS, NCT03362385) enrolled ACS patients. OSA defined as an apnea-hypopnea index ≥15 events/h. The effects of OSA on subsequent cardiovascular outcomes were evaluated across varying Lp(a) thresholds. Coronary plaque features by coronary computed tomography angiography were also analyzed. A total of 1137 patients were enrolled, 608 patients (53.5%) were diagnosed with OSA. At a median follow-up of 3.6 years, OSA was associated with a higher risk of major adverse cardiovascular and cerebrovascular events (MACCE) in patients with Lp(a) level > median (HR 1.59, 95% CI 1.12-2.26, p=.009), but not in patients with Lp(a) level ≤ median (HR 1.09, 95% CI 0.80-1.49, p=.60). There were consistent increases in HRs for MACCE in the OSA group with Lp(a) levels rising, as stratified by tertiles or quartiles of Lp(a). In patients with Lp(a) level > median, OSA demonstrated a higher prevalence of ≥1 high-risk plaque (HRP) feature (51.4% vs. 33.3%, p=.03) and low-attenuation plaque (50.0% vs. 32.8, p=.04) per vessel than non-OSA. OSA was associated with a continuously increased cardiovascular risk and a higher prevalence of HRP features as Lp(a) levels rose. Lp(a) may help identify ACS patients at higher cardiovascular risk, in whom the efficacy of OSA treatment should be further investigated. Show less

Fear of disease progression (FoP) is a common psychological concern among patients with unruptured intracranial aneurysms (UIAs). However, heterogeneity in FoP and the role of psychological resilience before treatment remain insufficiently understood. In this cross-sectional study, patients with UIAs scheduled for endovascular treatment were recruited. FoP was assessed using the Fear of Progression Questionnaire-Short Form (FoP-Q-12), and psychological resilience was measured with the Connor-Davidson Resilience Scale (CD-RISC-25). Latent profile analysis (LPA) was conducted to identify distinct FoP profiles. Least Absolute Shrinkage and Selection Operator (LASSO) regression followed by multinomial logistic regression were used to examine factors associated with profile membership. Five distinct FoP profiles were identified: Minimal Fear-Good Adjustment, Mild Emotionally Elevated Fear, Moderate Emotionally Reactive Fear, Moderate Functionally Concerned Fear, and High Pervasive Fear. Multinomial logistic regression showed that higher psychological resilience-particularly the tenacity dimension-was associated with lower odds of belonging to the Mild Emotionally Elevated Fear, Moderate Emotionally Reactive Fear, and Moderate Functionally Concerned Fear profiles, compared with the Minimal Fear-Good Adjustment profile. No significant association was observed between tenacity and the High Pervasive Fear profile. Sensitivity analyses using alternative resilience indicators yielded consistent results. Among patients with UIAs prior to endovascular treatment, FoP exhibits marked heterogeneity. Psychological resilience, especially tenacity, is differentially associated with specific FoP profiles. These findings support the value of profile-based psychological assessment to inform targeted psychosocial support during treatment planning. Show less

Neuroplasticity, the brain's capacity to adapt and reorganize in response to experiences and environmental changes, is fundamental to cognitive aging. As individuals age, cognitive functions such as memory, processing speed, and executive function commonly decline, driven largely by changes in neuroplasticity mechanisms like synaptic plasticity, neurogenesis, and functional reorganization. Synaptic plasticity is a well-established mechanism supporting learning and memory across the lifespan, whereas adult neurogenesis, robustly demonstrated in rodents, remains highly limited and controversial in the adult and aged human brain, with evidence largely restricted to rare post-mortem observations and injury-associated conditions. Functional reorganization allows the brain to adapt to structural changes, helping to preserve cognitive function despite age-related decline. Several factors, including oxidative stress, neuroinflammation, and hormonal shifts, exacerbate the decline in neuroplasticity, accelerating cognitive deterioration. Various interventions, including cognitive training, physical exercise, and pharmacological approaches, have demonstrated the potential to promote neuroplasticity and support cognitive health in aging populations. However, one of the major challenges is tailoring these interventions to the unique needs of individuals, as well as identifying novel therapeutic targets for intervention. To effectively address the cognitive decline associated with aging, future research should focus on developing personalized strategies and innovative techniques to enhance or modulate specific neuroplasticity-related processes under defined conditions in the aging brain. These advancements may provide better tools for delaying, mitigating, or even reversing age-related cognitive decline, improving quality of life for older individuals. Show less

Accurate measurement of lipoprotein(a)-cholesterol [Lp(a)-C] may be useful in interpreting the traditional lipid panel, particularly in patients with high Lp(a). We developed and analytically validated a direct immunocapture ELISA in a Clinical Laboratory Improvement Amendments-certified laboratory for quantifying Lp(a)-C in human plasma using an apolipoprotein(a)-specific monoclonal antibody (LPA4) coupled to magnetic beads. The linearity of the assay was found to be excellent (R Show less

To evaluate the lipid-lowering efficacy, safety, and adherence of switching from moderate- or low-intensity statin monotherapy to ezetimibe 10 mg/rosuvastatin 2.5 mg in Korean patients with type 2 diabetes mellitus (T2DM) and dyslipidaemia. This multicentre, open-label, single-arm, prospective study enrolled adults with T2DM and LDL-C ≥70 mg/dL despite ≥12 weeks of moderate or low-intensity statin therapy. Participants received ezetimibe 10 mg/rosuvastatin 2.5 mg once daily for 12 weeks. The primary endpoint was the proportion achieving LDL-C <70 mg/dL at Week 12. Secondary endpoints included changes in lipid and glycaemic parameters, subgroup analyses, and safety outcomes. Of 639 screened patients, 586 were included in the full analysis set (FAS). At Week 12, 62.3% (95% CI 58.4-66.2) achieved LDL-C <70 mg/dL. Mean LDL-C decreased by 26.0% from 90.9 ± 17.2 to 67.3 ± 19.3 mg/dL (p < 0.001). Total cholesterol, non-HDL-C, and apoB decreased significantly (all p < 0.001); HDL-C and triglycerides were unchanged (p = 0.914 and p = 0.393, respectively). HbA1c increased by 0.15 ± 0.53% and fasting glucose by 3.6 ± 24.7 mg/dL (both p < 0.001). HOMA-IR decreased by -0.22 ± 3.09, not significant (p = 0.085). Subgroup analyses showed greater LDL-C reductions in patients with BMI <23 kg/m Switching to ezetimibe 10 mg/rosuvastatin 2.5 mg achieved substantial LDL-C reductions, high goal attainment, excellent adherence, and good tolerability in Korean T2DM patients with dyslipidaemia. Show less

The transition from pre-reading to early word reading skill in early childhood is a time of profound developmental change. To understand changes in brain networks associated with reading development, this study examined individual differences in functional connectivity for reading at the start of formal literacy instruction. Sixty-six kindergarteners (ages 5-6) completed a visual word processing task during functional magnetic resonance imaging (fMRI). Based on standardized literacy assessments, participants were characterized as Pre-Readers (alphabetic knowledge but unable to read words) or Beginning Readers (some word reading ability). We compared patterns of task-based functional connectivity between children at different stages of literacy development using confirmatory subgroup Group Iterative Multilevel Model Estimation (cs-GIMME). cs-GIMME is a data-driven method that estimates individualized network connections between a priori regions of interest. Pre- and Beginning Readers did not differ in overall network complexity (number of functional connections between regions of interest). However, distinct periods of reading development corresponded to differences in network centrality, defined as the proportion of network connections involving specific regions of interest. Pre-Readers had more distributed connections and greater within-right hemisphere connectivity. In comparison, Beginning Readers demonstrated more symmetrical network organization, and greater centrality of the Visual Word Form Area and other left hemisphere language hubs. Increased reading skill was linearly associated with increased left lateralization, potentially reflecting more mature networks and greater print processing efficiency. These findings provide novel insights into child brain development during the first year of formal schooling by revealing links between emerging literacy skills and functional neural connectivity. Show less

Nurses in traditional Chinese medicine (TCM) departments face significant sleep challenges associated with occupational stressors. However, person-centered analyses classifying these sleep patterns remain scarce. This study aimed to identify heterogeneous sleep disturbance subgroups via latent profile analysis (LPA) and evaluate the performance of explainable machine learning models in discriminating these subgroups based on demographic and occupational features. A cross-sectional survey enrolled 7721 nurses from 130 TCM healthcare institutions in Liaoning Province (December 2024). Data encompassed demographic, occupational, and psychological variables obtained via self-administered questionnaires, including the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance short form 8a. LPA was employed to categorize sleep disturbance patterns. Recursive feature elimination with random forest (RFE-RF) was used to select features associated with subgroup membership for five machine learning models. Models were trained on 70% of the data and evaluated on a 30% independent test set. The optimal classification model (XGBoost) underwent interpretability analysis using Shapley additive explanations (SHAP). LPA identified three subgroups: mild-stable (29.8%), moderate-fluctuating (60%), and severe-persistent (10.2%). Machine learning models achieved test AUCs of 0.71-0.84, with XGBoost demonstrating the highest discriminatory performance (AUC = 0.84, 95%CI: 0.83-0.85) in classifying subgroups. SHAP analysis indicated that monthly income, organizational support, hospital level, self-compassion, and resilience were the top five features contributing to the model's classification output. This study characterized three distinct sleep disturbance subgroups among TCM nurses, with the majority exhibiting moderate symptoms. The sequential application of LPA and explainable machine learning demonstrated robust performance in distinguishing sleep disturbance patterns. Identifying correlates-such as lower income and resilience-may assist nurse managers in stratifying risk and tailoring interventions for those most likely to fall into the severe subgroup. Future longitudinal studies are required to validate the stability of these subgroups and establish causal relationships. Show less

China's total fertility rate has reached a critically low level, dropping to approximately 1.0 by the end of 2023which is significantly below the population replacement level of 1.5. This decline reflects a marked reduction in fertility intention among reproductive-aged women, exacerbating population aging and threatening long-term labor supply and social sustainability. Despite policy adjustments and governmental support initiatives, intended outcomes have not been realized. Current literature largely focuses on isolated determinants of fertility intention, overlooking heterogeneity within the population. Moreover, the pathways through which psychosocial factors operate across different subgroups remain poorly understood. Data for this study were derived from the 2021 Psychological and Behavioral Investigation of Chinese Residents (PBICR 2021), a nationally representative cross-sectional survey. Latent profile analysis (LPA) was employed to identify subtypes of fertility intention among reproductive-aged women, followed by multinomial logistic regression, which examined factors associated with different profiles. Among 2,973 reproductive-aged female participants, three distinct fertility intention profiles were identified via latent profile analysis: the Fertility Intention Decline Group (25.1%), the Low Fertility Intention Group (51.3%), and the High Fertility Intention Group (23.6%). Multinomial logistic regression analysis revealed that, compared with the Fertility Intention Decline Group, the Low Fertility Intention Group was significantly associated with family type, aged 20-40 years, residential location, having 2 children, and retirement status (all Fertility intention among reproductive-aged women demonstrates significant heterogeneity. This study identified three distinct latent profiles, each characterized by unique patterns of influencing factors. The findings highlight the necessity of moving beyond one-size-fits-all policy approaches and emphasize the importance of developing tailored interventions that account for the specific characteristics and determinants of each subgroup. Show less

Lysophosphatidic acid (LPA) is a cell-signaling lipid that has been proposed as an early-stage biomarker for ovarian cancer (OC). Diagnosing OC in Stage I is critical to improving patient outcomes, increasing the survival rate from 30% (when diagnosed in late stages of the disease) to over 90%. This significant improvement is due to the success of early interventions; however, current diagnostic methods are not as effective at early-stage detection, with only 15% of cases diagnosed in Stage I and over 70% diagnosed in Stage III or IV. There is a strong need for LPA detection that is sensitive, specific, rapid, low-cost, and automated to truly validate its effectiveness as a diagnostic characteristic for OC. We report the preliminary development and characterization of one such biosensor, which makes use of the advantages of magnetic particles and chemiluminescence for quick, sensitive detection of LPA. The sensor has proven to be viable, with a positive response to LPA concentration, a measurement time of 5 s after incubation, and an LOD of 3.5 nM. Show less