Sequential mediation analysis of physical activity, healthy diet, BMI, and academic burnout in the Pakistani educational landscape.

Research has indicated a negative impact of physical activity on academic burnout among students, however, there is a paucity of evidence about the underlying mechanism of this association in Pakistani students. The present research seeks to investigate the relationship between physical activity and academic burnout by investigating the potential mediating effects of adherence to the Mediterranean diet (MD) and body mass index (BMI). A sample of 596 students using a cross-sectional survey design was gathered from two public universities (Riphah International University and Mohammed Ali Jinnah University) in Rawalpindi, Pakistan from June to July 2022. The study participants were asked to fill out the Physical Activity Rating Scale-3, the Learning Burnout Scale, and the Test of Adherence to MD questionnaires. The study employed descriptive, bivariate, and path analysis through regression utilizing the SPSS software version 27. The findings demonstrated a negative correlation between academic burnout and BMI, physical activity, and adherence to the MD. The relationship between physical activity and academic burnout was mediated by BMI. Physical activity and academic burnout were inversely correlated, with adherence to the MD and BMI interacting as sequential mediators. The outcomes of this research have expanded our knowledge of the association between physical activity and academic burnout and have suggested crucial and appropriate strategies for addressing student academic burnout.

Potential determinants of parental hesitancy to vaccinate their children against COVID-19 infection: a cross-sectional investigation.

Coronavirus disease 2019 (COVID-19) vaccination hesitancy has emerged as a substantial concern among the adult population globally. However, limited evidence is available about parental hesitancy to vaccinate their children against COVID-19 within the Pakistani context. Thus, the present investigation aimed to assess parental attitudes, perceptions, and willingness regarding vaccination hesitancy and associated predictors of getting their children vaccinated against COVID-19. We conducted a cross-sectional population-based, self-administered online questionnaire in Punjab, Pakistan, on randomly selected parents between October 2022 and February 2023. The data were collected based on socio-demographics, attitudes, perceptions, and willingness of parents regarding COVID-19 vaccine hesitancy for their children. Adjusted odds ratios with 95% confidence intervals were estimated to identify the predictors of vaccine hesitancy. The findings demonstrated that among 1,478 participants, a total of 40% believed that the COVID-19 vaccine may pose a greater risk to children than adults, while 38% exhibited no concerns. Around 13% of children were not vaccinated in our study sample. More than half expressed hesitancy toward vaccination, and only 35.25% were inclined to get their children vaccinated in our study sample. In addition, only 16% of the parents believed that the COVID-19 vaccination may cause an alteration in their children's DNA. A similar proportion of parents were aware of the significance of getting their children vaccinated and expressed their willingness to vaccinate their children to prevent the COVID-19 infection. However, a higher odds ratio was observed in females with a higher educational background and those in the healthcare profession. In conclusion, healthcare awareness-supporting programs for educating parents should be designed and implemented. These insights might aid in the development of strategies to eradicate barriers in existing coronavirus vaccination programs and may vaccinate a larger child population to reduce the adverse consequences of the pandemic.

Overexpression of Nta-miR6155 confers resistance to Phytophthora nicotianae and regulates growth in tobacco (Nicotiana tabacum L.).

Tobacco black shank induced by Phytophthora nicotianae causes significant yield losses in tobacco plants. MicroRNAs (miRNAs) play a pivotal role in plant biotic stress responses and have great potential in tobacco breeding for disease resistance. However, the roles of miRNAs in tobacco plants in response to P. nicotianae infection has not been well characterized. In this study, we found that Nta-miR6155, a miRNA specific to Solanaceae crops, was significantly induced in P. nicotianae infected tobacco. Some of predicted target genes of Nta-miR6155 were also observed to be involved in disease resistance. To further investigate the function of miR6155 in tobacco during P. nicotianae infection, Nta-miR6155 overexpression plants (miR6155-OE) were generated in the Honghua Dajinyuan tobacco variety (HD, the main cultivated tobacco variety in China). We found that the Nta-miR6155 overexpression enhanced the resistance in tobacco towards P. nicotianae infections. The level of reactive oxygen species (ROS) was significantly lower and antioxidant enzyme activities were significantly higher in miR6155-OE plants than those in control HD plants during P. nicotianae infection. In addition, we found that the accumulation of salicylic acid and the expression of salicylic acid biosynthesis and signal transduction-related genes is significantly higher in miR6155-OE plants in comparison to the control HD plants. Furthermore, we found that Nta-miR6155 cleaved target genes NtCIPK18 to modulate resistance towards P. nicotianae in tobacco plants. Additionally, phenotypic analysis of miR6155-OE plants showed that Nta-miR6155 could inhibit the growth of tobacco by suppressing nitrogen uptake and photosynthesis. In conclusion, our findings indicated that miR6155 plays a crucial role in the regulation of growth and resistance against P. nicotianae infections in tobacco plants.

Mechanoluminescent Materials Enable Mechanochemically Controlled Atom Transfer Radical Polymerization and Polymer Mechanotransduction.

Organic mechanophores have been widely adopted for polymer mechanotransduction. However, most examples of polymer mechanotransduction inevitably experience macromolecular chain rupture, and few of them mimic mussel's mechanochemical regeneration, a mechanically mediated process from functional units to functional materials in a controlled manner. In this paper, inorganic mechanoluminescent (ML) materials composed of CaZnOS-ZnS-SrZnOS: Mn2+ were used as a mechanotransducer since it features both piezoelectricity and mechanolunimescence. The utilization of ML materials in polymerization enables both mechanochemically controlled radical polymerization and the synthesis of ML polymer composites. This procedure features a mechanochemically controlled manner for the design and synthesis of diverse mechanoresponsive polymer composites.

The longitudinal change pattern of cognitive subtypes in medication-free patients with major depressive disorder: a cluster analysis.

This study aimed to investigate whether there are different cognitive subtypes in patients with major depressive disorder (MDD) and the change pattern of cognitive clusters across the course of MDD. A battery of comprehensive cognitive tests was used to assess the executive function, processing speed, attention, and memory of 153 medication-free patients and 142 healthy controls (HCs). After 6 months of treatment with antidepressants, 87 patients completed cognitive tests again. K-means cluster analysis was performed to determine the cognitive subtypes. A preserved cognition cluster and an impaired cognition cluster were identified in the acute episode phase and the 6-month follow-up phase. 80.5% of the patients remained in their original subgroup after 6 months of treatment. The impaired cognition cluster during the 6-month follow-up period could be predicted by impaired cognition during the episode phase, disease state (remission or non-remission), current illness duration, and education level. This study supporting the heterogeneity of cognitive performance across the course of disease in patients with MDD using cluster analysis. It was found that cognitive impairment during depressive episodes was predictive of poorer cognitive performance even after treatment with antidepressants. Therefore, interventions targeting cognitive function from the early stages of MDD is essential.

Minimal change disease with papillary thyroid carcinoma: a report of two adult cases.

BACKGROUND: Minimal change disease (MCD), a pathological type of nephrotic syndrome (NS), can occur in patients with tumors. We report two adult cases of MCD associated with papillary thyroid carcinoma (PTC), known to be extremely rare in adults. CASE PRESENTATION: A 35-year-old female patient was simultaneously diagnosed with MCD and PTC. The MCD was effectively treated with thyroidectomy and prednisone.In addition, a 50-year-old male patient, who had been diagnosed with PTC three years prior, had MCD confirmed by renal biopsy. The patient achieved complete remission following treatment with tacrolimus and rituximab. CONCLUSIONS: The present case report describes and discusses the diagnostic and treatment processes employed in these two patients. Clinicians need to be aware of the renal effects of treating patients with solid tumors.

Tribochemically Controlled Atom Transfer Radical Polymerization Enabled by Contact Electrification.

Traditional mechanochemically controlled reversible-deactivation radical polymerization (RDRP) utilizes ultrasound or ball milling to regenerate activators, which induce side reactions because of the high-energy and high-frequency stimuli. Here, we propose a facile approach for tribochemically controlled atom transfer radical polymerization (tribo-ATRP) that relies on contact-electro-catalysis (CEC) between titanium oxide (TiO2 ) particles and CuBr2 /tris(2-pyridylmethylamine (TPMA), without any high-energy input. Under the friction induced by stirring, the TiO2 particles are electrified, continuously reducing CuBr2 /TPMA into CuBr/TPMA, thereby conversing alkyl halides into active radicals to start ATRP. In addition, the effect of friction on the reaction was elucidated by theoretical simulation. The results indicated that increasing the frequency could reduce the energy barrier for the electron transfer from TiO2 particles to CuBr2 /TPMA. In this study, the design of tribo-ATRP was successfully achieved, enabling CEC (ca. 10 Hz) access to a variety of polymers with predetermined molecular weights, low dispersity, and high chain-end fidelity.

Empirical evidence for the neurocognitive effect of nitrous oxide as an adjunctive therapy in patients with treatment resistant depression: A randomized controlled study.

Nitrous oxide (N2O) has demonstrated an antidepressant effect for treatment-resistant depression (TRD), but no studies investigated the effects of N2O on different cognition domains. This study aimed to test whether N2O would display pro-cognitive effects. We conducted a double-blinded, placebo-controlled, randomized controlled trial, 44 patients with TRD were randomized to N2O group (one-hour inhalation of 50% N2O/50% oxygen) or placebo group (50% air/50% oxygen). Thirty-four patients completed cognitive tests at the pre-treatment phase, 1-week, and 2 weeks post-treatment including subjective cognitive function, processing speed, attention, and executive function. Although the antidepressant effect of N2O was not significant at 1 week, patients still showed better performance of executive function at 1 week after receiving N2O compared with the placebo. Moreover, this significant improvement still existed at 1 week after controlling for the change in depressive symptoms over-time. Additionally, no significant difference was observed in subjective cognitive function, processing speed, and attention between these two groups across the 2-week follow-up period. As the first study investigating the treatment effects of N2O on improving cognitive function in TRD patients, the current study indicated that N2O has a potential pro-cognitive effect on executive function and this effect might be independent from improvements in depressive symptoms.

Effect of fluvoxamine on plasma interleukin-6 in patients with major depressive disorder: a prospective follow-up study.

Introduction: Major depressive disorder (MDD) is associated with low-grade inflammation, and anti-inflammatory treatment can help improve depressive symptoms. A recent study found that fluvoxamine (FLV) can reduce Interleukin-6 (IL-6) production via sigma-1 receptor in inflammation models. However, the anti- IL-6 effect of FLV in treating patients with MDD and whether it can contribute to antidepressant effects remain unclear. Methods: A total of 65 patients with MDD and 34 healthy controls were recruited at baseline, and 50 patients completed the FLV treatment for 2 months. We assessed depression and anhedonia and collected plasma IL-6 levels at baseline, 1 month, and 2 months after baseline. This study evaluated the changes in clinical measures and IL-6 during treatment and analyzed their association. Further subgroup analyses were conducted in patients with MDD with high, medium, or low IL-6. Results: Depression and anhedonia were significantly improved in patients with MDD, while the IL-6 did not significantly change after the FLV treatment. However, IL-6 significantly declined after the FLV treatment among patients with MDD with higher baseline IL-6. No significant associations were found between the changes in depressive symptoms and IL-6. Conclusion: Our study provided preliminary evidence suggesting that the anti-IL-6 effect of FLV might not play a vital role in its antidepressant treatment, at least in patients with MDD with low inflammation. However, for patients with MDD with higher IL-6, FLV can help reduce IL-6 significantly in the antidepressant treatment, which may help guide the individual treatment of MDD with higher IL-6 levels. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04160377, identifier NCT04160377.

The percentage of cognitive impairment in patients with major depressive disorder over the course of the depression: A longitudinal study.

BACKGROUND: Cognitive impairments (CI) are prevalent and persistent in patients with major depressive disorder (MDD). There is a lack of longitudinal studies exploring the changes of the percentage of CI among MDD patients before and after a long-term antidepressant treatment and the risk factors that predict the residual CI. METHODS: A neurocognitive battery was performed to assess four domains of cognitive function, including executive function, processing speed, attention, and memory. CI was set as cognitive performance scoring 1.5 SDs lower than the mean scores of healthy controls (HCs). Logistic regression models were conducted to examine the risk factors for the after-treatment residual CI. RESULTS: Over 50 % of patients showed at least one kind of CI. After the antidepressant treatment, the overall cognitive performance among remitted MDD patients was identical to HCs, however, there were still 24 % of the remitted MDD patients had at least one type of CI, especially in executive function and attention. Additionally, the percentage of CI among non-remitted MDD patients was still significantly different from HCs. Our regression analysis further identified that except for the non-remission of MDD, CI at baseline could also predict the residual CI in MDD patients. LIMITATIONS: A relatively high drop-out rate at follow-ups. CONCLUSIONS: Cognitive impairment in executive function and attention is persistent even in remitted patients with MDD, and baseline cognitive performance can predict the post-treatment cognitive performance. Our findings emphasize the integral role of early cognitive intervention in MDD treatment.

Relationship between childhood maltreatment and cognitive function in medication-free patients with major depressive disorder.

This study aimed to elucidate the contribution of childhood maltreatment (CM) and the disease of major depressive disorder (MDD) on cognitive function in medication-free patients in a current depressive episode, and to examine the effect of CM on the improvement of cognitive function after treatment with antidepressants. One hundred and fifty-three unmedicated patients with MDD and 142 healthy controls (HCs) underwent clinical interviews. CM assessment was performed using the Childhood Trauma Questionnaire (CTQ), and a battery of comprehensive neurocognitive tests was used to assess the participants' executive function, processing speed, attention, and memory. After 6 months of treatment with antidepressants, the neurocognitive tests were reperformed in patients with MDD and HCs. There was a significant main effect of MDD on all four cognitive domains, while the main effect of CM was only significant on memory. No significant interactive effect was found between MDD and CM on any of the cognitive domains. In the MDD group, higher CTQ total score was predictive of poorer memory performance. After treatment, significant main effects of treatment and MDD were found on all four cognitive domains in remitted patients with MDD. No significant main effect of CM or three-way interaction effect of treatment × MDD × CM was found on any of the cognitive domains. The disease of MDD contributed to impairments in all four cognitive domains. CM independently contributed to memory impairment in patients in a current depressive episode, with higher severity of CM predictive of poorer memory performance.

The value of nurse-led anthropometric and oropharyngeal measurements combined with STOP-Bang questionnaire in screening for obstructive sleep apnea in patients with acute coronary syndrome: a prospective cohort study.

BACKGROUND: Obstructive sleep apnea (OSA) is a modifiable risk factor for acute coronary syndrome (ACS), with high prevalence but low diagnostic rates. Therefore, it is particularly important to develop strategies for better screening for OSA in newly admitted ACS patients. METHODS: From March 2017 to October 2019, consecutive eligible patients with ACS underwent cardiorespiratory polygraphy during hospitalization. OSA was defined as an apnea-hypopnea index (AHI) ≥ 15 events/h. All anthropometric and oropharyngeal parameters are measured by specialist nurses. RESULTS: Finally, 761 ACS patients were recruited in the present study. Prevalence of moderate/severe OSA was 53.2% based on diagnostic criteria of AHI ≥ 15. Correlation analysis illustrated that AHI was positively correlated with anthropometric characteristics. In the multivariate model, only micrognathia (OR 2.02, 95% CI 1.02-4.00, P = 0.044), waist circumference (OR 1.08, 95% CI 1.04-1.11, P < 0.001), and STOP-BANG Questionnaire (SBQ) score (OR 1.45, 95% CI 1.27-1.66, P < 0.001) were independently associated with the prevalence of OSA. Receiver operating characteristic curve (ROC) analysis showed that the area under curve (AUC) of multivariable joint diagnosis (waist circumference, micrognathia combined with SBQ) was significantly better than the AUC of Epworth Sleepiness Scale (ESS) and SBQ (p < 0.0001 and p = 0.0002, respectively), and the results showed that AUC was 0.728. Under the optimal truncation value, the sensitivity was 73%, and the specificity was 61%, which was higher than the single index. Finally, we also constructed a nomogram model based on multiple logistic regression, to easily determine the probability of OSA in ACS patients. CONCLUSIONS: The new screening tool has greater power than single questionnaire or measurements in screening of OSA among ACS patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03362385, registered December 5, 2017.

The emerging role of long non-coding RNAs in schizophrenia.

Schizophrenia (SZ) is a severe psychiatric disorder which is contributed by both genetic and environmental factors. However, at present, its specific pathogenesis is still not very clear, and there is a lack of objective and reliable biomarkers. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are involved in the pathophysiology of several psychiatric disorders, including SZ, and hold promise as potential biomarkers and therapeutic targets for psychiatric disorders. In this review, we summarize and discuss the role of lncRNAs in the pathogenesis of SZ and their potential value as biomarkers and therapeutic targets.

Efficacy and safety of nitrous oxide for patients with treatment-resistant depression, a randomized controlled trial.

Nitrous oxide (N2O), an N-methyl-D-aspartate glutamate receptor antagonist, has demonstrated a rapid-onset antidepressant effect for treatment-resistant depression (TRD) preliminarily in the United States. This study aimed to test the efficacy and safety of N2O for TRD patients in China. In this double-blinded, placebo-controlled trial, 44 patients with TRD were randomized to receive a one-hour inhalation of a mixture of either 50% N2O/50% oxygen (N2O group) or 50% air/50% oxygen (placebo group). The primary outcome was the change on the 17-item Hamilton Depression Rating Scale (HDRS-17) over a course of two weeks. Using modified intention-to-treat analysis, the between group difference was found in the HDRS-17 score at two hours and 24 h after inhalation treatment, while no significant difference was found in week one and week two. Patients receiving N2O reported a significantly higher number of adverse events. All the adverse events lasted for no more than 24 h. No serious adverse events were reported. A single inhalation of 50% N2O effectively alleviates depression in patients with TRD in China. The efficacy lasts for no more than one week. N2O is safe for patients with TRD.

Bidirectional relationship between nocturnal subjective sleep duration and cognitive performance in Chinese over 45 years old: a national representative longitudinal study.

INTRODUCTION: Previous studies have inconsistent associations between changes in sleep duration and cognitive function and have not separated interindividual effects from intraindividual effects. This study aimed to examine the bidirectional associations between subjective night sleep duration and cognitive function while differing intraindividual and interindividual effects. METHODS: A national representative sample was obtained from China Health and Retirement Longitudinal Study during 2011-2018. Night sleep duration and potential confounders were assessed and collected by questionnaires. Cognition was assessed in three categories (orientation, executive function, and memory), and z scores were used for global cognitive performance. The random intercept cross-lagged panel model was used to examine the temporal associations during 2011-2018. RESULTS: Across 9404 participants over 45, at interindividual level, moderate (ß= -0.014) and long sleepers (ß= -0.06) had positive association between sleep duration and cognitive decline after adjusted covariates, but short sleepers had negative associations between sleep duration and cognitive decline (ß = 0.87). At intraindividual level, prolonged sleep duration predicted better cognition for short (ß= -0.021 at wave2-3; ß= -0.04 at wave3-4) and moderate (ß= -0.017 at wave3-4) sleepers. CONCLUSION: For short sleepers, longer subjective nocturnal sleep duration predicted better cognitive performance; but moderate and long sleepers showed opposite results-short and moderate sleepers with prolonged subjective nocturnal sleep duration would have later cognitive decline. Our findings tentatively suggested that an increased subjective night sleep duration and subjective long sleep duration could be regarded as useful tools for identifying middle- and old adults at higher risks of progressing to cognitive decline.

Exploration of the relationship between hippocampus and immune system in schizophrenia based on immune infiltration analysis.

Immune dysfunction has been implicated in the pathogenesis of schizophrenia (SZ). Despite previous studies showing a broad link between immune dysregulation and the central nervous system of SZ, the exact relationship has not been completely elucidated. With immune infiltration analysis as an entry point, this study aimed to explore the relationship between schizophrenia and the immune system in more detail from brain regions, immune cells, genes, and pathways. Here, we comprehensively analyzed the hippocampus (HPC), prefrontal cortex (PFC), and striatum (STR) between SZ and control groups. Differentially expressed genes (DEGs) and functional enrichment analysis showed that three brain regions were closely related to the immune system. Compared with PFC and STR, there were 20 immune-related genes (IRGs) and 42 immune pathways in HPC. The results of immune infiltration analysis showed that the differential immune cells in HPC were effector memory T (Tem) cells. The correlation of immune-related DEGs (IDEGs) and immune cells further analysis showed that NPY, BLNK, OXTR, and FGF12, were moderately correlated with Tem cells. Functional pathway analysis indicated that these four genes might affect Tem by regulating the PI3K-AKT pathway and the neuroactive ligand-receptor interaction pathway. The receiver operating characteristic curve (ROC) analysis results indicated that these four genes had a high diagnostic ability (AUC=95.19%). Finally, the disease animal model was successfully replicated, and further validation was conducted using the real-time PCR and the western blot. These results showed that these gene expression changes were consistent with our previous expression profiling. In conclusion, our findings suggested that HPC in SZ may be more closely related to immune disorders and modulate immune function through Tem, PI3K-Akt pathway, and neuroactive ligand-binding receptor interactions. To the best of our knowledge, the Immucell AI tool has been applied for the first time to analyze immune infiltration in SZ, contributing to a better understanding of the role of immune dysfunction in SZ from a new perspective.

High efficiency of left superior frontal gyrus and the symptom features of major depressive disorder. / å·¦ä¾§é¢ä¸Šå›žç½‘ç»œèŠ‚ç‚¹é«˜æ•ˆçŽ‡å€¼ä¸ŽæŠ‘éƒç—‡ç—‡çŠ¶ç‰¹å¾çš„å ³ç³».

OBJECTIVES: Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment. METHODS: Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (ei) and degree (ki). RESULTS: Repeated measures 2-factor ANCOVA showed significant main effects on group on the ei and ki values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the ei and ki values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher ei and ki values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher ei and ki values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher ei and ki values of LSFG (P=0.019 and P=0.026, respectively), and higher ei value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher ei values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the ei and ki values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the ki value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment. CONCLUSIONS: There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high ei of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased ei and ki values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.

Enhanced Resting-State Functional Connectivity of the Nucleus Accumbens in First-Episode, Medication-Naïve Patients With Early Onset Schizophrenia.

There is abundant evidence that early onset schizophrenia (EOS) is associated with abnormalities in widespread regions, including the cortical, striatal, and limbic areas. As a main component of the ventral striatum, the nucleus accumbens (NAc) is implicated in the pathology of schizophrenia. However, functional connection patterns of NAc in patients with schizophrenia, especially EOS, are seldom explored. A total of 78 first-episode, medication-naïve patients with EOS and 90 healthy controls were recruited in the present study, and resting-state, seed-based functional connectivity (FC) analyses were performed to investigate temporal correlations between NAc and the rest of the brain in the two groups. Additionally, correlation analyses were done between regions showing group differences in NAc functional integration and clinical features of EOS. Group comparison found enhanced FC of the NAc in the EOS group relative to the HCs with increased FC in the right superior temporal gyrus and left superior parietal gyrus with the left NAc region of interest (ROI) and elevated FC in left middle occipital gyrus with the right NAc ROI. No significant associations were found between FC strength and symptom severity as well as the age of the patients. Our findings reveal abnormally enhanced FC of the NAc with regions located in the temporal, parietal, and occipital areas, which were implicated in auditory/visual processing, sensorimotor integration, and cognitive functions. The results suggest disturbed relationships between regions subserving reward, salience processing, and regions subserving sensory processing as well as cognitive functions, which may deepen our understanding of the role of NAc in the pathology of EOS.

Disassociated and concurrent structural and functional abnormalities in the drug-naïve first-episode early onset schizophrenia.

Schizophrenia which is an abnormally developmental disease has been widely reported to show abnormal brain structure and function. Enhanced functional integration is a predominant neural marker for brain mature. Abnormal development of structure and functional integration may be a biomarker for early diagnosis of schizophrenia. Fifty-five patients with early onset schizophrenia (EOS) and 79 healthy controls were enrolled in this study. Voxel-based morphometry (VBM) and functional connectivity density (FCD) were performed to explore gray matter volume (GMV) lesion, abnormal functional integration, and concurrent structural and functional abnormalities in the brain. Furthermore, the relationships between abnormalities structural and function and clinical characteristics were evaluated in EOS. Compared with healthy controls, EOS showed significantly decreased GMV in the bilateral OFC, frontal, temporal, occipital, parietal and limbic system. EOS also showed decreased FCD in precuneus and increased FCD in cerebellum. Moreover, we found concurrent changes of structure and function in left lateral orbitofrontal cortex (lOFC). Finally, correlation analyses did not find significant correlation between abnormal neural measurements and clinical characteristic in EOS. The results reveal disassociated and bound structural and functional abnormalities patterns in EOS suggesting structural and functional measurements play different roles in delineating the abnormal patterns of EOS. The concurrent structural and functional changes in lOFC may be a biomarker for early diagnosis of schizophrenia. Our findings will deepen our understanding of the pathophysiological mechanisms in EOS.

lncRNA Mirt1: A Critical Regulatory Factor in Chronic Intermittent Hypoxia Exaggerated Post-MI Cardiac Remodeling.

Chronic intermittent hypoxia (CIH) is the main feature of obstructive sleep apnea (OSA) and is known to exaggerate cardiac remodeling after myocardial infarction (MI). However, the specific contribution of CIH to overall OSA-induced pathological complications and the transcriptomic mechanisms underlying CIH-exaggerated post-MI remodeling remains unclear. In this study, we used RNA-sequencing to construct the expression profiles of cardiac mRNAs, microRNAs, and long non-coding RNAs (lncRNA) in four groups of C57BL/6J mice (Sham, CIH, MI, MI + CIH) to evaluate how CIH regulates cardiac remodeling after MI. Compared with the other three groups, the MI + CIH group exhibited 345 lncRNAs, 35 microRNAs, and 5,220 differentially expressed mRNAs. Further analysis showed that CIH led to significant changes in Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the differentially expressed mRNAs. Co-expression network analysis identified two core lncRNAs (Mirt1 and AC125351.1) and two core microRNAs (miR-466i-5p and miR-574-5p) during the development of CIH-exaggerated post-MI remodeling, and they were verified by quantitative real-time PCR (qRT-PCR). LncRNA-mRNA correlation analysis further showed that lncRNA Mirt1 was positively correlated with Apbb1ip and Lcp2. In addition, microRNA-mRNA correlation analysis showed that microRNA miR-466i-5p was positively correlated with Snai2, Cdc27, and Ngfr. Furthermore, combining with lncRNA-mRNA and miRNA-mRNA networks, 44 RNAs were identified in the competitive endogenous RNA (ceRNA) network. Mirt1 acts as a ceRNA to bind to miR-466i-5p to further regulate the expression levels of the target gene, thereby aggravating cardiac remodeling after MI. In conclusion, our study provides a systematic perspective on the potential functions of mRNAs, microRNAs, and lncRNAs in CIH-exaggerated post-MI cardiac remodeling. Our data suggest that lncRNA Mirt1 may be the most critical regulator of MI aggravated by CIH.