Progesterone induces neuroprotection associated with immune/inflammatory modulation in experimental traumatic brain injury.

An imbalance of immune/inflammatory reactions aggravates secondary brain injury after traumatic brain injury (TBI) and can deteriorate clinical prognosis. So far, not enough therapeutic avenues have been found to prevent such an imbalance in the clinical setting. Progesterone has been shown to regulate immune/inflammatory reactions in many diseases and conveys a potential protective role in TBI. This study was designed to investigate the neuroprotective effects of progesterone associated with immune/inflammatory modulation in experimental TBI. A TBI model in adult male C57BL/6J mice was created using a controlled contusion instrument. After injury, the mice received consecutive progesterone therapy (8 mg/kg per day, i.p.) until euthanized. Neurological deficits were assessed via Morris water maze test. Brain edema was measured via the dry-wet weight method. Immunohistochemical staining and flow cytometry were used to examine the numbers of immune/inflammatory cells, including IBA-1 + microglia, myeloperoxidase + neutrophils, and regulatory T cells (Tregs). ELISA was used to detect the concentrations of IL-1ß, TNF-α, IL-10, and TGF-ß. Our data showed that progesterone therapy significantly improved neurological deficits and brain edema in experimental TBI, remarkably increased regulatory T cell numbers in the spleen, and dramatically reduced the activation and infiltration of inflammatory cells (microglia and neutrophils) in injured brain tissue. In addition, progesterone therapy decreased the expression of the pro-inflammatory cytokines IL-1ß and TNF-α but increased the expression of the anti-inflammatory cytokine IL-10 after TBI. These findings suggest that progesterone administration could be used to regulate immune/inflammatory reactions and improve outcomes in TBI.

Compositional features analysis by machine learning in genome represents linear adaptation of monkeypox virus.

Introduction: The global headlines have been dominated by the sudden and widespread outbreak of monkeypox, a rare and endemic zoonotic disease caused by the monkeypox virus (MPXV). Genomic composition based machine learning (ML) methods have recently shown promise in identifying host adaptability and evolutionary patterns of virus. Our study aimed to analyze the genomic characteristics and evolutionary patterns of MPXV using ML methods. Methods: The open reading frame (ORF) regions of full-length MPXV genomes were filtered and 165 ORFs were selected as clusters with the highest homology. Unsupervised machine learning methods of t-distributed stochastic neighbor embedding (t-SNE), Principal Component Analysis (PCA), and hierarchical clustering were performed to observe the DCR characteristics of the selected ORF clusters. Results: The results showed that MPXV sequences post-2022 showed an obvious linear adaptive evolution, indicating that it has become more adapted to the human host after accumulating mutations. For further accurate analysis, the ORF regions with larger variations were filtered out based on the ranking of homology difference to narrow down the key ORF clusters, which drew the same conclusion of linear adaptability. Then key differential protein structures were predicted by AlphaFold 2, which meant that difference in main domains might be one of the internal reasons for linear adaptive evolution. Discussion: Understanding the process of linear adaptation is critical in the constant evolutionary struggle between viruses and their hosts, playing a significant role in crafting effective measures to tackle viral diseases. Therefore, the present study provides valuable insights into the evolutionary patterns of the MPXV in 2022 from the perspective of genomic composition characteristics analysis through ML methods.

Preventing prefrontal dysfunction by tDCS modulates stress-induced creativity impairment in women: an fNIRS study.

Stress is a major external factor threatening creative activity. The study explored whether left-lateralized activation in the dorsolateral prefrontal cortex manipulated through transcranial direct current stimulation could alleviate stress-induced impairment in creativity. Functional near-infrared spectroscopy was used to explore the underlying neural mechanisms. Ninety female participants were randomly assigned to three groups that received stress induction with sham stimulation, stress induction with true stimulation (anode over the left and cathode over the right dorsolateral prefrontal cortex), and control manipulation with sham stimulation, respectively. Participants underwent the stress or control task after the transcranial direct current stimulation manipulation, and then completed the Alternative Uses Task to measure creativity. Behavioral results showed that transcranial direct current stimulation reduced stress responses in heart rate and anxiety. The functional near-infrared spectroscopy results revealed that transcranial direct current stimulation alleviated dysfunction of the prefrontal cortex under stress, as evidenced by higher activation of the dorsolateral prefrontal cortex and frontopolar cortex, as well as stronger inter-hemispheric and intra-hemispheric functional connectivity within the prefrontal cortex. Further analysis demonstrated that the cortical regulatory effect prevented creativity impairment induced by stress. The findings validated the hemispheric asymmetry hypothesis regarding stress and highlighted the potential for brain stimulation to alleviate stress-related mental disorders and enhance creativity.

Risk Assessment of the Possible Intermediate Host Role of Pigs for Coronaviruses with a Deep Learning Predictor.

Swine coronaviruses (CoVs) have been found to cause infection in humans, suggesting that Suiformes might be potential intermediate hosts in CoV transmission from their natural hosts to humans. The present study aims to establish convolutional neural network (CNN) models to predict host adaptation of swine CoVs. Decomposing of each ORF1ab and Spike sequence was performed with dinucleotide composition representation (DCR) and other traits. The relationship between CoVs from different adaptive hosts was analyzed by unsupervised learning, and CNN models based on DCR of ORF1ab and Spike were built to predict the host adaptation of swine CoVs. The rationality of the models was verified with phylogenetic analysis. Unsupervised learning showed that there is a multiple host adaptation of different swine CoVs. According to the adaptation prediction of CNN models, swine acute diarrhea syndrome CoV (SADS-CoV) and porcine epidemic diarrhea virus (PEDV) are adapted to Chiroptera, swine transmissible gastroenteritis virus (TGEV) is adapted to Carnivora, porcine hemagglutinating encephalomyelitis (PHEV) might be adapted to Primate, Rodent, and Lagomorpha, and porcine deltacoronavirus (PDCoV) might be adapted to Chiroptera, Artiodactyla, and Carnivora. In summary, the DCR trait has been confirmed to be representative for the CoV genome, and the DCR-based deep learning model works well to assess the adaptation of swine CoVs to other mammals. Suiformes might be intermediate hosts for human CoVs and other mammalian CoVs. The present study provides a novel approach to assess the risk of adaptation and transmission to humans and other mammals of swine CoVs.

Genomic representation predicts an asymptotic host adaptation of bat coronaviruses using deep learning.

Introduction: Coronaviruses (CoVs) are naturally found in bats and can occasionally cause infection and transmission in humans and other mammals. Our study aimed to build a deep learning (DL) method to predict the adaptation of bat CoVs to other mammals. Methods: The CoV genome was represented with a method of dinucleotide composition representation (DCR) for the two main viral genes, ORF1ab and Spike. DCR features were first analyzed for their distribution among adaptive hosts and then trained with a DL classifier of convolutional neural networks (CNN) to predict the adaptation of bat CoVs. Results and discussion: The results demonstrated inter-host separation and intra-host clustering of DCR-represented CoVs for six host types: Artiodactyla, Carnivora, Chiroptera, Primates, Rodentia/Lagomorpha, and Suiformes. The DCR-based CNN with five host labels (without Chiroptera) predicted a dominant adaptation of bat CoVs to Artiodactyla hosts, then to Carnivora and Rodentia/Lagomorpha mammals, and later to primates. Moreover, a linear asymptotic adaptation of all CoVs (except Suiformes) from Artiodactyla to Carnivora and Rodentia/Lagomorpha and then to Primates indicates an asymptotic bats-other mammals-human adaptation. Conclusion: Genomic dinucleotides represented as DCR indicate a host-specific separation, and clustering predicts a linear asymptotic adaptation shift of bat CoVs from other mammals to humans via deep learning.

CCL17 acts as an antitumor chemokine in micromilieu-driven immune skewing.

BACKGROUND: Chemokines are critical players in the local immune responses to tumors. CCL17 (thymus and activation-regulated chemokine, TARC) and CCL22 (macrophage-derived chemokine, MDC) can attract CCR4-bearing cells involving the immune landscape of cancer. However, their direct roles and functional states in tumors remain largely unclear. METHODS: We analyzed the lymphoma-related scRNA-seq and bulk RNA-seq datasets and identified the CCL17/CCL22-CCR4 axis as the unique participant of the tumor microenvironment. Then we edited the A20 lymphoma cell line to express CCL17 and CCL22 and assessed their function using three mouse models (Balb/C mouse, Nude mouse, and NSG mouse). In addition, we retrospectively checked the relationship between the CCL17/CCL22-CCR4 axis and the survival rates of cancer patients. RESULTS: The active CCL17/CCL22-CCR4 axis is a distinctive feature of the Hodgkin lymphoma microenvironment. CCR4 is widely expressed in immune cells but highly exists on the surface of NK, NKT, and Treg cells. The tumor model of Balb/C mice showed that CCL17 acts as an anti-tumor chemokine mediated by activated T cell response. In addition, the tumor model of Nude mice showed that CCL17 recruits NK cells for inhibiting lymphoma growth and enhances the NK-cDC1 interaction for resisting IL4i1-mediated immunosuppression. Interestingly, CCL17-mediated antitumor immune responses depend on lymphoid lineages but not mainly myeloid ones. Furthermore, we found CCL17/CCL22-CCR4 axis cannot be regarded as biomarkers of poor prognosis in most cancer types from the TCGA database. CONCLUSION: We provided direct evidence of antitumor functions of CCL17 mediated by the recruitment of conventional T cells, NKT cells, and NK cells. Clinical survival outcomes of target gene (CCL17, CCL22, and CCR4) expression also identified that CCL17/CCL22-CCR4 axis is not a marker of poor prognosis.

What's behind deliberation? The effect of task-related mind-wandering on post-incubation creativity.

Previous studies have already suggested that the deliberate nature of Mind-Wandering (MW) is critical for promoting creative performance. However, the deliberate nature of MW may be mixed up with task-relatedness. Whether the deliberate nature or task-relatedness of MW is responsible for such positive influence remains unclear. The present study tried to address this issue by investigating the influence of deliberate MW (MW-d) and task-related MW (MW-r) on post-incubation creative performance. Our result showed that MW-d is positively correlated with MW-r and spontaneous MW (MW-s) is highly positively correlated with task-unrelated MW (MW-u). Meanwhile, after controlling the possible confounding variables (i.e., the pre-incubation creative performance, the performance during distraction task, and motivation on creative ideation), both MW-d and MW-r predicted participants' AUT performance after incubation. However, the prediction model based on MW-r was stable while the MW-d-based prediction model was not. These findings indicate that the task-relatedness of MW, instead of its deliberate nature, might have a positive influence on subsequent creative performance.

Reduced brain activity and functional connectivity during creative idea generation in individuals with smartphone addiction.

Since the coronavirus disease 2019 outbreak, the frequency of smartphone use has surged, which has caused an increase in smartphone addiction among individuals. Smartphone addiction can impair various cognitive abilities. However, to date, the impact of smartphone addiction on creative cognition remains unclear. The current functional near-infrared spectroscopy study compared neural differences between smartphone addiction tendency (SAT) and healthy control (HC) individuals during creative idea generation. In particular, by manipulating a key component of creative cognition, that is, overcoming semantic constraints, we explored whether SAT individuals could overcome semantic constraints. Both the SAT and HC groups completed the alternate uses task (AUT) in semantic constraint and unconstraint conditions. The results indicated that the prefrontal cortex (PFC) and temporal regions were less active during AUT in the SAT group than in the HC group. In the SAT group, the PFC was less active under constraint than unconstraint conditions. Moreover, both task-related and resting-state functional connectivity analyses indicated weaker coupling between the PFC and temporal regions in the SAT than in the HC group. Furthermore, the left dorsolateral PFC mediated the effect of smartphone addiction on creative performance. These findings provide unprecedented neuroimaging evidence on the negative impact of smartphone addiction on creative cognition.

Establishment and Application of a Novel In Vitro Model of Microglial Activation in Traumatic Brain Injury.

Mechanical impact-induced primary injury after traumatic brain injury (TBI) leads to acute microglial pro-inflammatory activation and consequently mediates neurodegeneration, which is a major secondary brain injury mechanism. However, the detailed pathologic cascades have not been fully elucidated, partially because of the pathologic complexity in animal TBI models. Although there are several in vitro TBI models, none of them closely mimic post-TBI microglial activation. In the present study, we aimed to establish an in vitro TBI model, specifically reconstituting the pro-inflammatory activation and associated neurodegeneration following TBI. We proposed three sets of experiments. First, we established a needle scratch injured neuron-induced microglial activation and neurodegeneration in vitro model of TBI. Second, we compared microglial pro-inflammatory cytokines profiles between the in vitro TBI model and TBI in male mice. Additionally, we validated the role of injured neurons-derived damage-associated molecular patterns in amplifying microglial pro-inflammatory pathways using the in vitro TBI model. Third, we applied the in vitro model for the first time to characterize the cellular metabolic profile of needle scratch injured-neuron-activated microglia, and define the role of metabolic reprogramming in mediating pro-inflammatory microglial activation and mediated neurodegeneration. Our results showed that we successfully established a novel in vitro TBI model, which closely mimics primary neuronal injury-triggered microglial pro-inflammatory activation and mediated neurodegeneration after TBI. This in vitro model provides an advanced and highly translational platform for dissecting interactions in the pathologic processes of neuronal injury-microglial activation-neuronal degeneration cascade, and elucidating the detailed underlying cellular and molecular insights after TBI.SIGNIFICANCE STATEMENT Microglial activation is a key component of acute neuroinflammation that leads to neurodegeneration and long-term neurologic outcome deficits after TBI. However, it is not feasible to truly dissect primary neuronal injury-induced microglia activation, and consequently mediated neurodegeneration in vivo Furthermore, there is currently lacking of in vitro TBI models closely mimicking the TBI primary injury-mediated microglial activation. In this study, we successfully established and validated a novel in vitro TBI model of microglial activation, and for the first time, characterized the cellular metabolic profile of microglia in this model. This novel microglial activation in vitro TBI model will help in elucidating microglial inflammatory activation and consequently associated neurodegeneration after TBI.

The effects of social comparison and self-construal on creative idea generation: An EEG study.

Social comparisons usually occur in teams when members are tasked with generating creative ideas. However, it is unclear how these comparisons influence creative idea generation, which may be due to a lack of research on the interpretations of social comparison feedback. Self-construal is a psychological characteristic wherein individuals attempt to explain their cooperation and personal behaviours. Therefore, this study explored the influence of social comparison and self-construal on creative idea generation and the underlying neural mechanisms by recording electroencephalogram (EEG) activity. Individuals with independent and interdependent self-construal were randomly assigned to upward or downward comparison conditions and completed an alternative uses task. Results indicated that interdependent self-construal individuals had better originality and flexibility performance in the upward comparison condition compared to those in the downward comparison condition. The EEG results further revealed that, among interdependent self-construal individuals, the upward comparison condition elicited greater alpha synchronization in the bilateral frontal, right parietal, and right temporal regions compared to the downward comparison condition. Moreover, in the upward comparison condition, left frontal alpha synchronization mediated the effect of interdependent self-construal on creative idea generation. These findings support the notion of the joint effect of self-construal and social comparison on creative idea generation and suggest that interdependent self-construal individuals are better able to control irrelevant interfering information and form novel associations during an upward comparison situation compared to a downward comparison situation.

Addiction-Prone Personality and Creative Cognitive Styles: A Moderated Mediation Model of Novelty Seeking and Depression Tendency.

This study attempted to examine the mechanism of the impact of Addiction-Prone Personality (APP) on creative cognitive styles (idea generation, idea selection), especially to explore the mediating role of novelty seeking and the moderating role of depression tendency on the relationship between APP and creative cognitive styles. College students (N = 576, 79% female) participated in and completed measures of APP, idea generation and selection, novelty seeking, and depression tendency. Results showed that (1) APP was positively related with idea generation while negatively related with idea selection; (2) novelty seeking played a partial mediating role in the relationship between APP and idea generation and a suppressing effect between APP and idea selection; (3) depression tendency moderated the indirect relationship between APP and creative cognitive styles through novelty seeking. Therefore, APP has different indirect effects on idea generation and idea selection via novelty seeking. When there was a higher depression tendency, there was a stronger indirect effect. The study highlights the significant importance of the underlying processes between APP and creative cognitive styles and offers implications for rethinking the relationship between addiction and creativity.

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level.

BACKGROUND: Approximately 8-9% of the world's population is affected by autoimmune diseases, and yet the mechanism of autoimmunity trigger is largely understudied. Two unique cell death modalities, ferroptosis and pyroptosis, provide a new perspective on the mechanisms leading to autoimmune diseases, and development of new treatment strategies. METHODS: Using scRNA-seq datasets, the aberrant trend of ferroptosis and pyroptosis-related genes were analyzed in several representative autoimmune diseases (psoriasis, atopic dermatitis, vitiligo, multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn's disease, and experimental autoimmune orchitis). Cell line models were also assessed using bulk RNA-seq and qPCR. RESULTS: A substantial difference was observed between normal and autoimmune disease samples involving ferroptosis and pyroptosis. In the present study, ferroptosis and pyroptosis showed an imbalance in different keratinocyte lineages of psoriatic skinin addition to a unique pyroptosis-sensitive keratinocyte subset in atopic dermatitis (AD) skin. The results also revealed that pyroptosis and ferroptosis are involved in epidermal melanocyte destruction in vitiligo. Aberrant ferroptosis has been detected in multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn's disease, and autoimmune orchitis. Cell line models adopted in the study also identified pro-inflammatory factors that can drive changes in ferroptosis and pyroptosis. CONCLUSION: These results provide a unique perspective on the involvement of ferroptosis and pyroptosis in the pathological process of autoimmune diseases at the scRNA-seq level. IFN-γ is a critical inducer of pyroptosis sensitivity, and has been identified in two cell line models.

Generation and clinical potential of functional T lymphocytes from gene-edited pluripotent stem cells.

Engineered T cells have been shown to be highly effective in cancer immunotherapy, although T cell exhaustion presents a challenge for their long-term function. Additional T-cell sources must be exploited to broaden the application of engineered T cells for immune defense and reconstitution. Unlimited sources of pluripotent stem cells (PSCs) have provided a potential opportunity to generate precise-engineered therapeutic induced T (iT) cells. Single-cell transcriptome analysis of PSC-derived induced hematopoietic stem and progenitor cells (iHSPC)/iT identified the developmental pathways and possibilities of generating functional T cell from PSCs. To date, the PSC-to-iT platforms encounter several problems, including low efficiency of conventional T subset specification, limited functional potential, and restrictions on large-scale application, because of the absence of a thymus-like organized microenvironment. The updated PSC-to-iT platforms, such as the three-dimensional (3D) artificial thymic organoid (ATO) co-culture system and Runx1/Hoxa9-enforced iT lymphopoiesis, provide fresh perspectives for coordinating culture conditions and transcription factors, which may greatly improve the efficiency of T-cell generation greatly. In addition, the improved PSC-to-iT platform coordinating gene editing technologies will provide various functional engineered unconventional or conventional T cells. Furthermore, the clinical applications of PSC-derived immune cells are accelerating from bench to bedside.

The Interactive Model of L2 Listening Processing in Chinese Bilinguals: A Multiple Mediation Analysis.

Second language (L2) listening is a common challenge for language learners. It remains largely unknown how bilinguals process L2 listening. The literature has suggested an interactive model of L2 listening processing. However, few studies have examined the model from an experimental approach. The current study tried to provide empirical evidence for the interactive model of L2 listening processing in bilinguals by exploring the relationships among English spoken word segmentation (SWS), cognitive inhibition, cognitive flexibility, and L2 listening proficiency. The results showed positive associations among SWS, cognitive inhibition, cognitive flexibility, and L2 listening proficiency. Mediation analysis suggested that SWS might have a positive influence on L2 listening proficiency both directly and indirectly through cognitive inhibition and cognitive flexibility, respectively. These results imply that both bottom-up (reflected at SWS) and top-down (reflected at cognitive inhibition and flexibility) processes are engaged in bilinguals' L2 listening processing.

Neural mechanisms underlying the influence of retrieval ability on creating and recalling creative ideas.

Previous studies revealed a close relationship between retrieval ability and creative thinking; however, it is still unclear what processes of creative thinking are influenced by retrieval ability. This study applied a novel task paradigm to distinguish between different processes of creative thinking. We used functional near-infrared spectroscopy (fNIRS) to explore the differences of cortical activation and functional connectivity in the prefrontal cortex (PFC), temporoparietal junction (TPJ) and temporal cortex between high (HRA) and low (LRA) retrieval ability groups during creating original ideas (CO) and recalling original ideas (RO) tasks. The behaviour results revealed that in the CO task, the HRA group performed better than the LRA group on fluency, flexibility, and originality. Importantly, the fNIRS results further indicated that the HRA group exhibited higher activation of the l-TPJ, l-STG, l-MTG, r-FPC, r-DLPFC than the LRA group during the CO task. Moreover, the HRA group exhibited higher activation of the bilateral TPJ, l-STG, l-MTG, r-DLPFC, and r-FPC in the CO task than in the RO task, and the LRA group exhibited higher activation of the l-STG in the CO task than in the RO task. The functional connectivity between the PFC and IFG, TPJ, and MTG of the HRA group was significantly stronger than that of the LRA group in both the CO and RO tasks. The findings suggest that high retrieval ability could facilitate the generation of creative ideas by facilitating the retrieval of novel information and suppression of common information compared to low retrieval ability. This study provides neural evidence for the effect of different levels of retrieval ability on creative thinking.

CT-guided trans-sternal iodine-125 seeds implantation for masses in the anterior or middle mediastinum.

PURPOSE: The aim of this study was to explore the feasibility and clinical value of computed tomography (CT)-guided trans-sternal puncture to implant 125I seeds to treat masses in the anterior or middle mediastinum. MATERIAL AND METHODS: From September 2017 to December 2019, twenty patients with masses in the anterior or middle mediastinum were enrolled and treated with CT-guided trans-sternal 125I seeds implantation. Dosimetry parameters were compared between post-operative and pre-operative plans. Satisfaction rate of 125I seed distribution, complications, and local efficacy were evaluated. RESULTS: A total of 22 lesions were treated with 125I implantation in twenty patients, all procedures being successfully completed. The dosimetry parameters of the 20 patients immediately after surgery were as follows: mean D90 = 134.30 ±14.53 Gy; mean V90, V100, V150, and V200 were 96.10 ±1.55%, 92.69 ±1.93%, 66.86 ±7.53%, and 42.95 ±9.11%, respectively; mean conformity index (CI), external index (EI), and homogeneity index (HI) were 0.65 ±0.06, 40.79 ±13.72%, and 27.90 ±7.53%, respectively. The satisfaction rate of 125I seed distribution was 90%. The mean follow-up duration was 12 ±4.75 months (range, 4-24 months). The local control rates of 2 months, 6 months, and 1 year after surgery were 65.0%, 64.7%, and 53.8%, respectively. One patient had a small degree of pneumothorax, and one had hemoptysis after surgery. CONCLUSIONS: CT-guided trans-sternal puncture plant 125I seeds for the treatment of masses in the anterior or middle mediastinum might serve as an alternative approach for treating specific mediastinal metastatic tumors.

Affective valence moderates the influence of thinking style on insight problem solving: Electrophysiological evidence.

The present study examined whether affective valence moderated the influence of holistic and analytic thinking styles on insight problem solving by analysing event-related potentials (ERPs). Adult participants were screened and assigned to holistic-thinking and analytic-thinking groups, 22 participants per group. They completed the insight task. The results indicated that in the initial stage of insight, the positive affect elicited larger N1 amplitudes than the negative affect in the analytic-thinking group. Moreover, for the holistic-thinking group, positive affect elicited larger P2 amplitudes than negative affect. In the subsequent stages, negative affect elicited larger N300-500 and late components than positive affect in the holistic-thinking group. In contrast, positive affect elicited larger N300-500 and late components than negative affect in the analytic-thinking group. These findings suggest that holistic-thinking individuals with negative affect and analytic-thinking individuals with positive affect were more able to abandon mental sets and reconstruct novel mental representations.

Inter-brain neural mechanism underlying turn-based interaction under acute stress in women: a hyperscanning study using functional near-infrared spectroscopy.

With the ever-changing social environment, stress has exerted a substantial influence on social interaction. The present study examined the underlying cognitive and neural mechanism on how acute stress affected the real-time cooperative and competitive interaction with four hypothesized path models. We used the hyperscanning technique based on functional near-infrared spectroscopy (fNIRS) device to examine brain-to-brain coherence within the dyads engaging Pattern Game under acute stress manipulated through Trier Social Stress Test for Groups. Behavioral results showed stressed dyads exhibited better cooperative performance and higher self-other overlap level during the cooperative session than dyads in the control group. The fNIRS results identified higher interpersonal brain synchronization in the right temporal-parietal junction (r-TPJ) stronger Granger causality from partner-to-builder during the cooperative session in the stress group when compared with the control group. Our results corroborated better performance in the cooperative context and further identified that brain-to-brain coherence in r-TPJ and self-other overlap serially mediated the effect of acute stress on cooperative performance.

Polydatin protects neuronal cells from hydrogen peroxide damage by activating CREB/Ngb signaling.

Oxidative stress­induced neuronal cell death contributes significantly to the physiological processes of a number of neurological disorders. Polydatin (PD) has been reported to protect against Alzheimer's disease (AD), ischemic stroke and traumatic brain injury. However, the underlying neuroprotective mechanisms remain to be elucidated. The current study suggested that PD activates AKT/cAMP response element­binding protein (CREB) signaling and induces neuroglobin (Ngb) to protect neuronal cells from hydrogen peroxide (H2O2) in vitro. PD inhibited the H2O2­induced neuronal cell death of primary mouse cortical neurons and N2a cells. Functional studies showed that PD attenuated H2O2­induced mitochondrial dysfunction and mitochondrial reactive oxygen species production. Mechanistically, PD was verified to induce the phosphorylation of AKT and CREB and increase the protein level of Ngb. The luciferase assay results showed that Ngb transcriptional activity was activated by CREB, especially after PD treatment. It was further indicated that PD increased the transcription of Ngb by enhancing the binding of CREB to the promoter region of Ngb. Finally, Ngb knockdown largely attenuated the neuroprotective role of PD against H2O2. The results indicated that PD protected neuronal cells from H2O2 by activating CREB/Ngb signaling in neuronal cells, indicating that PD has a neuroprotective effect against neurodegenerative diseases.

Delayed rFGF21 Administration Improves Cerebrovascular Remodeling and White Matter Repair After Focal Stroke in Diabetic Mice.

Type 2 diabetes mellitus (T2DM) is a major comorbidity exacerbating ischemic brain injury and impairing post-stroke recovery. Our previous study suggested that recombinant human fibroblast growth factor (rFGF) 21 might be a potent therapeutic targeting multiple aspects of pathophysiology in T2DM stroke. This study aims to evaluate the potential effects of rFGF21 on cerebrovascular remodeling after T2DM stroke. Permanent distal middle cerebral artery occlusion was performed in heterozygous non-diabetic db/ + and homozygous diabetic db/db mice. Daily rFGF21 administration was initiated 1 week after stroke induction and maintained for up to 2 weeks thereafter. Multiple markers associated with post-stroke recovery, including angiogenesis, oligodendrogenesis, white matter integrity, and neurogenesis, were assessed up to 3 weeks after stroke. Our results showed an impairment in post-stroke vascular remodeling under T2DM condition, reflected by the decreased expression of trophic factors in brain microvessels and impairments of angiogenesis. The defected cerebrovascular remodeling was accompanied by the decreased oligodendrogenesis and neurogenesis. However, delayed rFGF21 administration normalized post-stroke hyperglycemia and improved neurological outcomes, which may partially be via the promotion of pro-angiogenic trophic factor expression in brain microvessels and cerebrovascular remodeling. The better cerebrovascular remodeling may also contribute to oligodendrogenesis, white matter integrity, and neurogenesis after T2DM stroke. Therefore, delayed rFGF21 administration may improve neurological outcomes in T2DM stroke mice, at least in part by normalizing the metabolic abnormalities and promoting cerebrovascular remodeling and white matter repair.