Galunisertib promotes bevacizumab-induced vascular normalization in nasopharyngeal carcinoma: Multi-parameter MRI evaluation.

Tumor vascular normalization (TVN) is associated with antitumor therapeutic efficacy in nasopharyngeal carcinoma (NPC). However, the short time window of TVN is the biggest hindrance to its wide clinical application. We investigated whether targeting transforming growth factor beta can enhance the TVN effect of bevacizumab (BEV)-induced patient-derived xenograft (PDX) models of NPC. We constructed mouse subcutaneous PDX models of NPC and classified the mice into four drug-treatment groups, namely placebo control, galunisertib, BEV, and galunisertib + BEV. We performed MRI multi-parameter examinations at different time points and evaluated the vascular density, vascular structure, and tumor hypoxia microenvironment by histopathology. The efficacy of chemotherapy and drug delivery was evaluated by administering cisplatin. We found that combined therapy with galunisertib and BEV significantly delayed tumor growth, enhanced the TVN effect, and improved chemotherapeutic efficacy compared with monotherapy. Mechanistically, galunisertib reversed the epithelial-mesenchymal transition process and inhibited the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor by downregulating LAMC2. Correlation analysis of MRI data and pathological indicators showed that there was a good correlation between them.

Association study of brain structure-function coupling and glymphatic system function in patients with mild cognitive impairment due to Alzheimer's disease.

Background: Mild cognitive impairment (MCI) is a critical transitional phase from healthy cognitive aging to dementia, offering a unique opportunity for early intervention. However, few studies focus on the correlation of brain structure and functional activity in patients with MCI due to Alzheimer's disease (AD). Elucidating the complex interactions between structural-functional (SC-FC) brain connectivity and glymphatic system function is crucial for understanding this condition. Method: The aims of this study were to explore the relationship among SC-FC coupling values, glymphatic system function and cognitive function. 23 MCI patients and 18 healthy controls (HC) underwent diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI). DTI analysis along the perivascular space (DTI-ALPS) index and SC-FC coupling values were calculated using DTI and fMRI. Correlation analysis was conducted to assess the relationship between Mini-Mental State Examination (MMSE) scores, DTI-ALPS index, and coupling values. Receiver operating characteristic (ROC) curves was conducted on the SC-FC coupling between the whole brain and subnetworks. The correlation of coupling values with MMSE scores was also analyzed. Result: MCI patients (67.74 ± 6.99 years of age) exhibited significantly lower coupling in the whole-brain network and subnetworks, such as the somatomotor network (SMN) and ventral attention network (VAN), than HCs (63.44 ± 6.92 years of age). Whole-brain network coupling was positively correlated with dorsal attention network (DAN), SMN, and visual network (VN) coupling. MMSE scores were significantly positively correlated with whole-brain coupling and SMN coupling. In MCI, whole-brain network demonstrated the highest performance, followed by the SMN and VAN, with the VN, DAN, limbic network (LN), frontoparietal network (FPN), and default mode network (DMN). Compared to HCs, lower DTI-ALPS index was observed in individuals with MCI. Additionally, the left DTI-ALPS index showed a significant positive correlation with MMSE scores and coupling values in the whole-brain network and SMN. Conclusion: These findings reveal the critical role of SC-FC coupling values and the ALPS index in cognitive function of MCI. The positive correlations observed in the left DTI-ALPS and whole-brain and SMN coupling values provide a new insight for investigating the asymmetrical nature of cognitive impairments.

Cerebral cortex functional reorganization in preschool children with congenital sensorineural hearing loss: a resting-state fMRI study.

Purpose: How cortical functional reorganization occurs after hearing loss in preschool children with congenital sensorineural hearing loss (CSNHL) is poorly understood. Therefore, we used resting-state functional MRI (rs-fMRI) to explore the characteristics of cortical reorganization in these patents. Methods: Sixty-three preschool children with CSNHL and 32 healthy controls (HCs) were recruited, and the Categories of Auditory Performance (CAP) scores were determined at the 6-month follow-up after cochlear implantation (CI). First, rs-fMRI data were preprocessed, and amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were calculated. Second, whole-brain functional connectivity (FC) analysis was performed using bilateral primary auditory cortex as seed points. Finally, Spearman correlation analysis was performed between the differential ALFF, ReHo and FC values and the CAP score. Results: ALFF analysis showed that preschool children with CSNHL had lower ALFF values in the bilateral prefrontal cortex and superior temporal gyrus than HCs, but higher ALFF values in the bilateral thalamus and calcarine gyrus. And correlation analysis showed that some abnormal brain regions were weak negatively correlated with CAP score (p < 0.05). The ReHo values in the bilateral superior temporal gyrus, part of the prefrontal cortex and left insular gyrus were lower, whereas ReHo values in the bilateral thalamus, right caudate nucleus and right precentral gyrus were higher, in children with CSNHL than HCs. However, there was no correlation between ReHo values and the CAP scores (p < 0.05). Using primary auditory cortex (PAC) as seed-based FC further analysis revealed enhanced FC in the visual cortex, proprioceptive cortex and motor cortex. And there were weak negative correlations between the FC values in the bilateral superior temporal gyrus, occipital lobe, left postcentral gyrus and right thalamus were weakly negatively correlated and the CAP score (p < 0.05). Conclusion: After auditory deprivation in preschool children with CSNHL, the local functions of auditory cortex, visual cortex, prefrontal cortex and somatic motor cortex are changed, and the prefrontal cortex plays a regulatory role in this process. There is functional reorganization or compensation between children's hearing and these areas, which may not be conducive to auditory language recovery after CI in deaf children.

Region-specific Cerebral Metabolic Alterations in Parkinson's Disease Patients With/without Mild Cognitive Impairment.

N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) are brain metabolites involved in some key neuronal functions within the brain, such as cognitive function. The aim of this study was to investigate whether Parkinson's disease (PD) with different cognitive status induces regional brain metabolite differences. 38 diagnosed PD patients, including 18 PD patients with normal cognitive (PDN), 20 PD subjects with cognitive impairment (PDMCI) and 25 healthy controls (HC) participated in this study. All subjects underwent a single-voxel proton MR spectroscopy (1H-MRS) on a 3T scanner. 1H-MRS were obtained from bilateral PCC, left thalamus and PFC regions in all subjects, respectively. Region-specific cerebral metabolic alterations existed in PD patients with different cognitive status. PDMCI patients showed a significant reduction of NAA, Cho and tCr in the PCC and left thalamus, compared to healthy controls; whereas lower levels of NAA and Cho in thalamus were found in PDN patients. Moreover, Cho and tCr levels were positively correlated with MMSE scores. Both NAA and tCr in PCC levels were positively correlated with MMSE and MoCA scores. The combination of thalamic and PCC metabolites showed a 75.6% accuracy in distinguishing PDMCI patients from PDN patients. This study provides preliminary evidence that thalamic, PCC and PFC neurometabolic alterations occur in PD patients with cognition decline. Findings of this study indicate that NAA and tCr abnormalities in PCC and thalamus might be used as a biomarker to track cognitive decline in Parkinson's disease in clinical settings.

Neural activation signatures in individuals with subclinical depression: A task-fMRI meta-analysis.

BACKGROUND: Previous task-related functional magnetic resonance imaging (task-fMRI) investigations have documented abnormal brain activation associated with subclinical depression (SD), defined as a clinically relevant level of depressive symptoms that does not meet the diagnostic criteria for major depressive disorder. However, these task-fMRI studies have not reported consistent conclusions. Performing a voxel-based meta-analysis of task-fMRI studies may yield reliable findings. METHODS: We extracted the peak coordinates and t values of included studies and analyzed brain activation between individuals with SD and healthy controls (HCs) using anisotropic effect-size signed differential mapping (AES-SDM). RESULTS: A systematic literature search identified eight studies, including 266 individuals with SD and 281 HCs (aged 14 to 25). The meta-analysis showed that individuals with SD exhibited significantly greater activation in the right lenticular nucleus and putamen according to task-fMRI. The meta-regression analysis revealed a negative correlation between the proportion of females in a group and activation in the right striatum. LIMITATIONS: The recruitment criteria for individuals with SD, type of tasks and MRI acquisition parameters of included studies were heterogeneous. The results should be interpreted cautiously due to insufficient included studies. CONCLUSION: Our findings suggest that individuals with SD exhibit increased activation in the right lenticular nucleus, putamen and striatum, which may indicate a compensatory increase in response to an impairment of insular and striatal function caused by depression. These results provide valuable insights into the potential pathophysiology of brain dysfunction in SD.

Social entrepreneurial intention among university students in China.

The issues of employment, social inequality, and resource scarcity can be effectively addressed through social entrepreneurship, contributing to the growing research interest on the formation of social entrepreneurial intention. Using the theory of planned behaviour, the current study examined the influence of selected key factors on social entrepreneurial intention among university students. Based on the cross-sectional quantitative research design, online survey was conducted, which involved 684 students and graduates from five universities in Southern China. The obtained results demonstrated the significant and positive influence of perceived values on sustainability, opportunity recognition competency, attitude towards entrepreneurship, subjective norms, and perceived behavioural control on social entrepreneurial intention. Additionally, attitude towards entrepreneurship partially mediated the relationships of risk-taking propensity, self-efficacy, and need for achievement on social entrepreneurial intention. The multi-group analysis results also showed that need for achievement and social entrepreneurial intention differed significantly between genders, which provides new ideas for future investigations into the impact of gender on social entrepreneurial intentions. Based on the findings of this study, it is crucial that university students are exposed to relevant courses or training to develop social entrepreneurship competencies and promote sustainable values. The findings of this study will provide policymakers with relevant policy guidelines and more effective theoretical support to achieve the goal of promoting social entrepreneurship among university students in a more resource-efficient and effective manner.