The relationship between autistic traits and the stress of social isolation: Development of an explanatory model.

Background: Social isolation can be particularly challenging for individuals with high autistic traits who struggle with social interactions. The COVID-19 pandemic led to increased isolation, exacerbating stress for those who may have difficulty in connecting with others. This study aimed to explore the relationship between autistic traits and stress associated with social isolation. Methods: A sample of 1597 Chinese adults completed measures of autistic traits, the stress of social isolation, psychological inflexibility and core self-evaluation, during an epidemic prevention and control period of COVID-19 in Chongqing, China. Measures included the Autism-Spectrum Quotient, Coronavirus Stress Measure, Acceptance and Action Questionnaire-II, and Core Self-Evaluation Scale. Results: Autistic traits were positively correlated with the stress of social isolation, which was mediated by the chain effect of core self-evaluation and psychological inflexibility. individuals with high autistic traits reported significantly higher stress than individuals with low autistic traits. Limitations: This was a cross-sectional study, which limits causal inference. In addition, data were self-reported, which may cause methodological effects. Finally, this study was conducted during China's quarantine policy and external validation of the findings is required. Conclusions: Autistic traits are positively associated with the stress of social isolation. Autistic traits affected core self-evaluation first, and psychological inflexibility subsequently, leading to the stress of social isolation. individuals with high autistic traits tended to experience higher levels of stress during pandemic quarantines. The findings provide useful evidence for developing interventions and implementing preventive measures to reduce stress in individuals with high autistic traits and autism spectrum disorder.

The effect of top-down attention on empathy fatigue.

Prolonged exposure to others' suffering can lead to empathy fatigue, especially when individuals struggle to effectively regulate their empathic capacity. Shifting active attention away from emotional components toward cognitive components of others' suffering is an effective strategy for mitigating empathy fatigue. This research investigated how top-down attentional manipulation modulates empathy fatigue in both auditory (Study 1) and visual (Study 2) modalities. Participants completed two tasks in both studies: (i) the attention to cognitive empathy task (A-C task) and (ii) the attention to emotional empathy task (A-E task). Each task included three blocks (Time Block 1, Time Block 2, and Time Block 3) designed to induce empathy fatigue. Study 1 revealed that the A-C task reduced empathy fatigue and N1 amplitudes than the A-E task in Time Block 3, indicating that attention to cognitive empathy might decrease auditory empathy fatigue. Study 2 indicates that the A-C task caused a longer N2 latency than the A-E task, signifying a decelerated emotional empathic response when attention was on cognitive empathy in the visual modality. Overall, prioritizing cognitive empathy seems to conserve mental resources and reduce empathy fatigue. This research documented the relationship between top-down attention and empathy fatigue and the possible neural mechanism.

The influence of aggressive exercise on responses to self-perceived and others' pain.

Previous studies have reported relationships between exercise and pain. However, little is known about how aggressive exercise modulates individuals' responses to their own and others' pain. This present study addresses this question by conducting 2 studies employing event-related potential (ERP). Study 1 included 38 participants whose self-perceived pain was assessed after intervention with aggressive or nonaggressive exercises. Study 2 recruited 36 participants whose responses to others' pain were assessed after intervention with aggressive or nonaggressive exercise. Study 1's results showed that P2 amplitudes were smaller, reaction times were longer, and participants' judgments were less accurate in response to self-perceived pain stimuli, especially to high-pain stimuli, after intervention with aggressive exercise compared to nonaggressive exercise. Results of study 2 showed that both P3 and LPP amplitudes to others' pain were larger after intervention with aggressive exercise than with nonaggressive exercise. These results suggest that aggressive exercise decreases individuals' self-perceived pain and increases their empathic responses to others' pain.

Research Progress in Immunotherapy of Gliomas.

Although some progress has been made in tumor treatment, gliomas remain one of the tumors that can still seriously threaten human life and health. Due to the particularity of the immune microenvironment of the central nervous system and the strong invasiveness of tumors, the treatment of gliomas remains a major challenge. Currently, researchers have explored a large number of immunotherapy programs to improve the survival and prognosis of glioma patients, including tumor vaccines, immune checkpoint inhibitors, adoptive cell transfer therapy, viral vector therapy, and genetic engineering therapy. The goal of these programs is to activate or change the immunosuppressive environment and target tumor cells through drugs, combined with surgical resection, radiotherapy, chemotherapy, and anti-angiogenesis drugs, to achieve the purpose of treating glioma. This review briefly describes the immunosuppressive microenvironment of gliomas and summarizes recent immunotherapeutic strategies and their progress. The aim is to summarize the latest immunotherapies for the treatment of gliomas and provide new research directions.

Wilforol A inhibits human glioma cell proliferation and deactivates the PI3K/AKT signaling pathway.

OBJECTIVES: To study the anti-proliferation activity of wilforol A against glioma cells and its possible molecular mechanisms. METHODS: Human glioma cell lines U118 MG and A172, human tracheal epithelial cells (TECs) and astrocytes (HAs) were exposed to various concentrations of wilforol A and evaluated for viability, apoptosis, and levels of proteins using WST-8 assay, flow cytometry and Western blot analysis, respectively. RESULTS: Wilforol A inhibited the growth of U118 MG and A172 cells, but not TECs and HAs, in a concentration-dependent manner and the estimated IC50 were 6 to 11 µM after 4 h-exposure. Apoptosis was induced at an apoptotic rate of about 40% at 100 µM in U118 MG and A172 cells, but the rates were less than 3% in TECs and HAs. Co-exposure to caspase inhibitor Z-VAD-fmk significantly reduced wilforol A-induced apoptosis. Wilforol A treatment also reduced the colony formation ability of U118 MG cells and triggered a significant increase in ROS production. Elevated levels of pro-apoptotic proteins p53, Bax and cleaved caspase 3 and reduced level of the anti-apoptotic protein Bcl-2 were observed in glioma cells exposed to wilforol A. The expression of PI3K and p-Akt genes in the PI3K/AKT pathways were significantly downregulated in glioma cells treated with wilforol A. CONCLUSIONS: Wilforol A inhibits the growth of glioma cells, reduces the levels of proteins in the P13K/Akt signal transduction pathways and increases the levels of pro-apoptotic proteins.

Examining the function of macrophage oxidative stress response and immune system in glioblastoma multiforme through analysis of single-cell transcriptomics.

Background: Glioblastoma (GBM), a prevalent malignant neoplasm within the neuro-oncological domain, has been a subject of considerable scrutiny. Macrophages, serving as the principal immunological constituents, profoundly infiltrate the microenvironment of GBM. However, investigations elucidating the intricate immunological mechanisms governing macrophage involvement in GBM at the single-cell level remain notably limited. Methods: We conducted a comprehensive investigation employing single-cell analysis, aiming to redefine the intricate cellular landscape within both the core and peripheral regions of GBM tumors. Our analytical focus extended to the profound study of macrophages, elucidating their roles within the context of oxidative stress, intercellular information exchange, and cellular trajectories concerning GBM and its assorted subpopulations. We pursued the identification of GBM prognostic genes intricately associated with macrophages. Utilizing experimental research to investigate the relevance of MANBA in the context of GBM. Results: Our investigations have illuminated the central role of macrophages in the intricate interplay among various subpopulations within the GBM microenvironment. Notably, we observed a pronounced intensity of oxidative stress responses within macrophages when compared to their GBM counterparts in other subpopulations. Moreover, macrophages orchestrated intricate cellular communication networks, facilitated by the SPP1-CD44 axis, both internally and with neighboring subpopulations. These findings collectively suggest the potential for macrophage polarization from an M1 to an M2 phenotype, contributing to immune suppression within the tumor microenvironment. Furthermore, our exploration unearthed GBM prognostic genes closely associated with macrophages, most notably MANBA and TCF12. Remarkably, MANBA appears to participate in the modulation of neuroimmune functionality by exerting inhibitory effects on M1-polarized macrophages, thereby fostering tumor progression. To bolster these assertions, experimental validations unequivocally affirmed the promotional impact of MANBA on GBM, elucidated through its capacity to curb cell proliferation, invasiveness, and metastatic potential. Conclusion: These revelations represent a pivotal step towards unraveling the intricate immunological mechanisms governing the interactions between macrophages and diverse subpopulations within the GBM milieu. Furthermore, they lay the foundation for the development of an innovative GBM prognostic model, with MANBA at its epicenter, and underscore the potential for novel immunotherapeutic targets in the ongoing pursuit of enhanced treatment modalities for this formidable malignancy.

Empathy for pain in individuals with autistic traits during observation of static and dynamic stimuli.

Previous studies have reported that individuals with autistic traits, like those with Autism Spectrum Disorder (ASD), may have impaired empathic responses when observing static stimuli of others' pain. However, it remains unclear whether individuals with autistic traits exhibit impaired empathy for pain in response to dynamic stimuli. The present study addressed this question by recruiting 529 individuals whose autistic traits were assessed using the autism-spectrum quotient (AQ) questionnaire. Thirty participants who scored within the top 10% and bottom 10% on the AQ were selected into High-AQ and Low-AQ groups, respectively. This study employed painful whole-body action pictures and videos as static and dynamic stimuli. Both groups were instructed to judge whether the models in the stimuli were experiencing pain, and their reaction times, accuracy and event-related potential (ERP) data were recorded. Results showed that the P2 amplitudes were larger in the High-AQ group than in the Low-AQ group when viewing painful static stimuli, while no difference between the two groups was found when viewing painful dynamic stimuli. These results suggest that autistic traits influenced the emotional processing of others' pain in response to static stimuli.

Single-Cell RNA Sequencing Reveals Cellular and Transcriptional Changes Associated With Traumatic Brain Injury.

Traumatic brain injury (TBI) is currently a substantial public health problem and one of the leading causes of morbidity and mortality worldwide. However, the cellular and transcriptional changes in TBI at single-cell level have not been well characterized. In this study, we reanalyzed a single-cell RNA sequencing (scRNA-seq) dataset of mouse hippocampus to identify the key cellular and transcriptional changes associated with TBI. Specifically, we found that oligodendrocytes were the most abundant cell type in mouse hippocampus, and detected an expanded astrocyte population, which was significantly activated in TBI. The enhanced activity of inflammatory response-related pathways in the astrocytes of TBI samples suggested that the astrocytes, along with microglia, which were the major brain-resident immune cells, were responsible for inflammation in the acute phase of TBI. Hormone secretion, transport, and exocytosis were found upregulated in the excitatory neurons of TBI, which gave us a hint that excitatory neurons might excessively transport and excrete glutamate in response to TBI. Moreover, the ependymal subpopulation C0 was TBI-specific and characterized by downregulated cilium movement, indicating that the attenuated activity of cilium movement following TBI might decrease cerebrospinal fluid flow. Furthermore, we observed that downregulated genes in response to candesartan treatment were preferentially expressed in excitatory neurons and were related to pathways like neuronal systems and neuroactive ligand-receptor interaction, indicating that candesartan might promote recovery of neurons after traumatic brain injury via mediating neuroactive ligand-receptor interactions and reducing excitotoxicity. In conclusion, our study identified key cell types in TBI, which improved our understanding of the cellular and transcriptional changes after TBI and offered an insight into the molecular mechanisms that could serve as therapeutic targets.

Application of Deep Learning Technology in Glioma.

A common and most basic brain tumor is glioma that is exceptionally dangerous to health of various patients. A glioma segmentation, which is primarily magnetic resonance imaging (MRI) oriented, is considered as one of common tools developed for doctors. These doctors use this system to examine, analyse, and diagnose appearance of the glioma's outward for both patients, i.e., indoor and outdoor. In the literature, a widely utilized approach for the segmentation of glioma is the deep learning-oriented method. To cope with this issue, a segmentation of glioma approach, i.e., primarily on the convolution neural networks, is developed in this manuscript. A DM-DA-enabled cascading approach for the segmentation of glioma, which is 2DResUnet-enabled model, is reported to resolve the problem of spatial data acquisition of insufficient 3D specifically in the 2D full CNN along with the core issue of memory consumption of 3D full CNN. For gliomas segmentation at various stages, we have utilized multiscale fusion approach, attention, segmentation, and DenseBlock. Moreover, for reducing three dimensionalities of the Unet model, a sampling of fixed region is used along with multisequence data of the glioma image. Finally, the CNN model has the ability of producing a better segmentation of tumor preferably with minimum possible memory. The proposed model has used BraTS18 and BraTS17 benchmark data sets for fivefold cross-validation (local) and online evaluation preferably official, respectively. Evaluation results have verified that edema's Dice Score preferable average, enhancement, and core areas of the segmentation of the glioma with DM-DA-Unet perform exceptionally well on the validation set of BraTS17. Finally, average sensitivity was observed to be high as well, which is approximately closer to the best segmentation model and its effect on the validation set of BraTS1 and has segmented gliomas accurately.

Herbal decoction of Gastrodia, Uncaria, and Curcuma confers neuroprotection against cerebral ischemia in vitro and in vivo.

"Tianma" (Gastrodia) and "gouteng" (Uncaria) are both widely used to treat cerebral ischemia. At the same time, "ezhu" (Curcuma longa) or turmeric, is derived from the dried roots of C. longa. It is a polyphenol known for its anti-inflammatory effects and its promotion of blood vessel endothelial function. This study explored the neuroprotective effects of a water extract of "tianma", "gouteng", and "ezhu" against ischemic injury. Flow cytometry analysis showed that Gastrodia, Uncaria, and Curcuma reduced the proportion of apoptotic cells in CoCl2 induced B35 (P = 0.0027) and SH-SY5Y (P = 0.0006) cell sample relative to the respective control group. Western blot indicated that Gastrodia, Uncaria, and Curcuma upregulated the expression of Bcl-2 and inversely downregulated Bax and Caspase-3 (P < 0.001). The infarct volume observed in the Gastrodia, Uncaria, and Curcuma group was also decreased compared with the control group (P < 0.05). Immunofluorescence detection revealed a lower expression of Caspase-7 in the Gastrodia, Uncaria, and Curcuma group than in the control group, while expression was negligible in the sham group. Gastrodia, Uncaria, and Curcuma confer neuroprotective effects in CoCl2 induced B35/SH-SY5Y cells and a rat model of ischemia by way of its anti-apoptotic effects.

Pak2 inhibition promotes resveratrol-mediated glioblastoma A172 cell apoptosis via modulating the AMPK-YAP signaling pathway.

As a polyphenolic compound, resveratrol (Res) is widely present in a variety of plants. Previous studies have shown that Res can inhibit various tumors. However, its role in c remains largely unexplored. In the present study, we first demonstrated that Res inhibited cell viability and induced apoptosis of glioblastoma A172 cell. Further experiments showed that Res induced mitochondrial dysfunction and activated the activity of caspase-9. Functional studies have found that Res treatment is associated with an increase in the expression of Pak2. Interestingly, inhibition of Pak2 could further augment the proapoptotic effect of Res. Mechanistically, Pak2 inhibition induced reactive oxygen species overproduction, mitochondria-JNK pathway activation, and AMPK-YAP axis suppression. However, overexpression of YAP could abolish the anticancer effects of Res and Pak2 inhibition, suggesting a necessary role played by the AMPK-YAP pathway in regulating cancer-suppressive actions of Res and Pak2 inhibition. Altogether, our results indicated that Res in combination with Pak2 inhibition could further enhance the anticancer property of Res and this effect is mediated via the AMPK-YAP pathway.

Fabrication of a Large-Area, Fused Polymer Micromold Based on Electric-Field-Driven (EFD) µ-3D Printing.

An electric-field-driven (EFD), µ-3D printed, fused polymer technique has been developed for the fabrication of large-area microscale prototype molds using typical polymer materials, including microcrystalline wax (MC-wax), polycaprolactone (PCL), and polymathic methacrylate (PMMA). This work proposes an alternative for large area microscale modes and overcomes the limitation of high cost in the traditional mold manufacturing industry. The EFD principle enables printing of fused polymers materials more than one order of magnitude lower than the nozzle diameter, contributing to the necking effect of the Taylor cone jet, which is the key factor to achieve the microscale manufacturing. Numerical simulation of electric field distribution between the meniscus and substrate was carried out to elucidate the dependence of electric field distribution on the meniscus condition of three types of polymers under printable voltage, and the electrical field parameters for the EFD µ-3D printing were determined. A number of experiments were printed successfully using a large range of viscosity materials, ranging from tens of mPa·s to hundreds of thousands of mPa·s of PCL and PMMA. The differences in parameters of different materials, such as viscosity, tensile properties, and surface energy, were studied to assess their use in different fields. Using proper process parameters and a nozzle with an inner diameter of 200 µm, three different application cases were completed, including a Wax microarray and microchannel with a minimum dot diameter of 20 µm, a PCL mesh structure with a minimum line width of 5 µm, and a PMMA large-area mold with a maximum aspect ratio of 0.8. Results show that the EFD µ-3D printing has the outstanding advantages of high printing resolution and polymer material universality.

CircFOXO3 promotes glioblastoma progression by acting as a competing endogenous RNA for NFAT5.

BACKGROUND: Circular RNAs (circRNAs), a newly discovered type of endogenous noncoding RNA, have been proposed to mediate the progression of diverse types of tumors. Systematic studies of circRNAs have just begun, and the physiological roles of circRNAs remain largely unknown. Here, we focused on elucidating the potential role and molecular mechanism of circular forkhead box O3 (circFOXO3) in glioblastoma (GBM) progression. METHODS: First, we analyzed circFOXO3 alterations in GBM and noncancerous tissues through real-time quantitative reverse transcription PCR (qRT-PCR). Next, we used loss- and gain-of-function approaches to evaluate the effect of circFOXO3 on GBM cell proliferation and invasion. Mechanistically, fluorescent in situ hybridization, RNA pull-down, dual luciferase reporter, and RNA immunoprecipitation assays were performed to confirm the interaction between circFOXO3 and miR-138-5p/miR-432-5p in GBM. An animal model was used to verify the in vitro experimental findings. RESULTS: CircFOXO3 expression was significantly higher in GBM tissues than in noncancerous tissues. GBM cell proliferation and invasion were reduced by circFOXO3 knockdown and enhanced by circFOXO3 overexpression. Further biochemical analysis showed that circFOXO3 exerted its pro-tumorigenic activity by acting as a competing endogenous RNA (ceRNA) to increase expression of nuclear factor of activated T cells 5 (NFAT5) via sponging both miR-138-5p and miR-432-5p. Notably, tumor inhibition by circFOXO3 downregulation could be reversed by miR-138-5p/miR-432-5p inhibitors in GBM cells. Moreover, GBM cells with lower circFOXO3 expression developed less aggressive tumors in vivo. CONCLUSIONS: Our data demonstrate that circFOXO3 can exert regulatory functions in GBM and that ceRNA-mediated microRNA sequestration might be a potential strategy for GBM therapy.

Melatonin ameliorates endoplasmic reticulum stress in N2a neuroblastoma cell hypoxia-reoxygenation injury by activating the AMPK-Pak2 pathway.

Endoplasmic reticulum (ER) stress has been identified as a primary factor involved in brain ischemia-reperfusion injury progression. p21-activated kinase 2 (Pak2) is a novel ER function regulator. The aim of our study is to explore the influence of Pak2 on ER stress and determine whether melatonin attenuates ER stress-mediated cell death by modulating Pak2 expression in vitro using N2a cells. The results of our study demonstrated that hypoxia-reoxygenation (HR) injury repressed the levels of Pak2, an effect that was accompanied by activation of ER stress. In addition, decreased Pak2 was associated with oxidative stress, calcium overload, and caspase-12-mediated apoptosis activation in HR-treated N2a cells. Interestingly, melatonin treatment reversed the decreased Pak2 expression under HR stress. Knockdown of Pak2 abolished the protective effects of melatonin on ER stress, oxidative stress, and caspase-12-related N2a cells death. Additionally, we found that Pak2 was regulated by melatonin via the AMPK pathway; inhibition of AMPK prevented melatonin-mediated Pak2 upregulation, a result that was accompanied by an increase in N2a cell death. Altogether, these results identify the AMPK-Pak2 axis as a new signaling pathway responsible for ER stress and N2a cell viability under HR injury. Modulation of the AMPK-Pak2 cascade via supplementation of melatonin might be considered an effective approach to attenuate reperfusion-mediated N2a cell damage via repression of ER stress.

Upregulation of LGMNP1 confers radiotherapy resistance in glioblastoma.

Glioblastoma is a lethal brain tumor type, which is frequently resistant to radiotherapy. The aim of the present study was to explore the function of legumain pseudogene 1 (LGMNP1) on radioresistance in glioblastoma. Reverse transcription­quantitative PCR was used to detect the relative expression of LGMNP1 in glioma cell lines after radiotherapy. Ectopic expression of LGMNP1 was achieved by transfection of a lentiviral vector. A clonogenic assay was used to determine the colony formation ability following radiotherapy. A comet assay, flow cytometry and western blot analysis were applied to detect DNA damage, the apoptotic rate, and levels of apoptotic proteins, respectively. The results revealed that LGMNP1 was significantly upregulated in glioma cells after radiation. Glioma cells stably overexpressing LGMNP1 were successfully established. Overexpression of LGMNP1 in glioma cells reduced DNA damage processes and the percentage of apoptotic cells after radiotherapy. In addition, overexpression of LGMNP1 in glioblastoma multiforme cells decreased apoptotic protein expression after radiotherapy. The present results indicated that upregulation of LGMNP1 conferred radiotherapy resistance by increasing the ability of DNA damage protection and reducing the apoptotic population in glioma cells.

Evaluating Degradation at Railway Crossings Using Axle Box Acceleration Measurements.

In this paper, we investigate the capability of an axle box acceleration (ABA) system to evaluate the degradation at railway crossings. For this purpose, information from multiple sensors, namely, ABA signals, 3D rail profiles, Global Positioning System (GPS) and tachometer recordings, was collected from both nominal and degraded crossings. By proper correlation of the gathered data, an algorithm was proposed to distinguish the characteristic ABA related to the degradation and then to evaluate the health condition of crossings. The algorithm was then demonstrated on a crossing with an unknown degradation status, and its capability was verified via a 3D profile measurement. The results indicate that the ABA system is effective at monitoring two types of degradations. The first type is uneven deformation between the wing rail and crossing nose, corresponding to characteristic ABA frequencies of 230-350 and 460-650 Hz. The second type is local irregularity in the longitudinal slope of the crossing nose, corresponding to characteristic ABA frequencies of 460-650 Hz. The types and severity of the degradation can be evaluated by the spatial distribution and energy concentration of the characteristic frequencies of the ABA signals.