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The level of endothelin-1 (ET-1), a potent vasoconstrictor, was associated with retinopathy under ischemia. The effects of endothelial endothelin-1 (ET-1) over-expression in a transgenic mouse model using Tie-1 promoter (TET-1 mice) on pathophysiological changes of retinal ischemia were investigated by intraluminal insertion of a microfilament up to middle cerebral artery (MCA) to transiently block the ophthalmic artery. Two-hour occlusion and twenty-two-hour reperfusion were performed in homozygous (Hm) TET-1 mice and their non-transgenic (NTg) littermates. Presence of pyknotic nuclei in ganglion cell layer (GCL) was investigated in paraffin sections of ipsilateral (ischemic) and contralateral (non-ischemic) retinae, followed by measurement of the thickness of inner retinal layer. Moreover, immunocytochemistry of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS) and aquaporin-4 (AQP4) peptides on retinal sections were performed to study glial cell reactivity, glutamate metabolism and water accumulation, respectively after retinal ischemia. Similar morphology was observed in the contralateral retinae of NTg and Hm TET-1 mice, whereas ipsilateral retina of NTg mice showed slight structural and cellular changes compared with the corresponding contralateral retina. Ipsilateral retinae of Hm TET-1 mice showed more significant changes when compared with ipsilateral retina of NTg mice, including more prominent cell death in GCL characterized by the presence of pyknotic nuclei, elevated GS immunoreactivity in Müller cell bodies and processes, increased AQP-4 immunoreactivity in Müller cell processes, and increased inner retinal thickness. Thus, over-expression of endothelial ET-1 in TET-1 mice may contribute to increased glutamate-induced neurotoxicity on neuronal cells and water accumulation in inner retina leading to edema.

We investigated the cardiovascular thrombotic risk after surgical castration （SC） versus genadotmpin-releasing hormone agonists （GnRHa） in Chinese men with prostate cancer. All Chinese prostate cancer patients who were treated with SC or GnRHa from year 2000 to 2009 were reviewed and compared. The primary outcome was any new-onset of cardiovascular thrombotic events after SC or GnRHa, which was defined as any event of acute myocardial infarction or ischemic stroke. The risk of new-onset cardiovascular thrombotic event was compared between the SC group and the GnRHa group using Kaplan-Meier method. Multivariate Cox regression analysis was performed to adjust for other potential confounding factors. A total of 684 Chinese patients was included in our study, including 387 patients in the SC group and 297 patients in the GnRHa group. The mean age in the SC group （75.3 ~ 7.5 years） was significantly higher than the GnRHa group （71.8 ~ 8.3 years） （P 〈 0.001）. There was increased risk of new cardiovascular thrombotic events in the SC group when compared to the GnRHa group upon Kaplan-Meier analysis （P= 0.014）. Upon multivariate Cox regression analysis, age （hazard ratio [HR] 1.072, 95% confidence interval [CI] 1.04-1.11, P 〈 0.001）, hyperlipidemia （HR 2.455, 95% Cl 1.53-3.93, P 〈 0.001）, and SC （HR 1.648, 95% CI 1.05-2.59, P = 0.031） were significant risk factors of cardiovascular thrombotic events. In conclusion, SC was associated with increased risk of cardiovascular thrombotic events when compared to GnRHa. This is an important aspect to consider while deciding on the method of androgen deprivation therapy, especially in elderly men with known history of hyperlipidemia.

This paper presents a study on the evaluation of hybrid learning and teaching practices by academics. A mixed research method involving a questionnaire survey and a focus group interview was employed to gather academics’ feedback on their experience in delivering hybrid instruction in a synchronous manner in which on-site and remote students attended classes simultaneously, their students’ hybrid learning effectiveness, and their suggestions for improvement. The questionnaire was administered to 76 academics from a university in Hong Kong where hybrid learning and teaching were implemented, and the focus group interview involved 10 academics. The findings reveal that the participating academics perceived themselves as having an overall high degree of readiness to handle technical issues. They expressed that the students from their hybrid classes had lower levels of interaction, engagement, and motivation than those from traditional face-to-face classes. The participants also reported their challenges regarding hybrid learning and teaching, including heavy workload for lesson preparation and face-to-face and online classroom management, unfamiliarity with interactive teaching design suitable for hybrid classes, and difficulties in monitoring students’ learning process. They provided suggestions for the improvement of hybrid classes, ranging from the provision of technological support to professional development for enhancing students’ online interaction and engagement. These findings contribute to revealing academics’ experience in practising hybrid learning and teaching and identifying ways to address their challenges.

Atypical sensory processing has recently gained much research interest as a key domain of autistic symptoms. Individuals with autism spectrum disorder (ASD) exhibit difficulties in processing the temporal aspects of sensory inputs, and show altered behavioural responses to sensory stimuli (i.e., sensory responsiveness). The present study examined the relation between sensory responsiveness (assessed by the Adult/Adolescent Sensory Profile) and audiovisual temporal integration (measured by unisensory temporal order judgement (TOJ) tasks and audiovisual simultaneity judgement (SJ) tasks) in typically-developing adolescents ( n  = 94). We found that adolescents with higher levels of autistic traits exhibited more difficulties in separating visual stimuli in time (i.e., larger visual TOJ threshold) and showed a stronger bias to perceive sound-leading audiovisual pairings as simultaneous. Regarding the associations between different measures of sensory function, reduced visual temporal acuity, but not auditory or multisensory temporal processing, was significantly correlated with more atypical patterns of sensory responsiveness. Furthermore, the positive correlation between visual TOJ thresholds and sensory avoidance was only found in adolescents with relatively high levels of autistic traits, but not in those with relatively low levels of autistic traits. These findings suggest that reduced visual temporal acuity may contribute to altered sensory experiences and may be linked to broader behavioural characteristics of ASD.

Unwillingness to exert effort for rewards has been found in patients with schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD), but the underlying shared and distinct reward neural mechanisms remain unclear. This study aimed to compare the neural correlates of such impairments across different diagnoses. The neural responses in an effort-expenditure for reward task (EEfRT) were assessed in 20 SCZ patients, 23 MDD patients, 17 BD patients, and 30 healthy controls (HC). The results found shared activation in the cingulate gyrus, the medial frontal gyrus, and the middle frontal gyrus during the EEfRT administration. Compared to HC, SCZ patients exhibited stronger variations of functional connectivity between the right caudate and the left amygdala, the left hippocampus and the left putamen, with increase in reward magnitude. In MDD patients, an enhanced activation compared to HC in the right superior temporal gyrus was found with the increase of reward magnitude. The variations of functional connectivity between the caudate and the right cingulate gyrus, the left postcentral gyrus and the left inferior parietal lobule with increase in reward magnitude were weaker than that found in HC. In BD patients, the degree of activation in the left precuneus was increased, but that in the left dorsolateral prefrontal cortex was decreased with increase in reward probability compared to HC. These findings demonstrate both shared and distinct reward neural mechanisms associated with EEfRT in patients with SCZ, MDD, and BD, implicating potential intervention targets to alleviate amotivation in these clinical disorders.

Background Lepidoptera (butterflies and moths) is one of the most geographically widespread insect orders in the world, and its species play important and diverse ecological and applied roles. Climate change is one of the biggest challenges to biodiversity this century, and lepidopterans are vulnerable to climate change. Temperature-dependent gene expression differences are of relevance under the ongoing climate crisis. However, little is known about how climate affects gene expression in lepidopterans and the ecological consequences of this, particularly with respect to genes with biased expression in one of the sexes. The common yellow butterfly, Eurema hecabe (Family Pieridae) , is one of the most geographically widespread lepidopterans that can be found in Asia, Africa, and Australia. Nevertheless, what temperature-dependent effects there may be and whether the effects differ between the sexes remain largely unexplored. Results Here, we generated high-quality genomic resources for E. hecabe along with transcriptomes from eight developmental stages. Male and female butterflies were subjected to varying temperatures to assess sex-specific gene expression responses through mRNA and microRNA transcriptomics. We find that there are more temperature-dependent sex-biased genes in females than males, including genes that are involved in a range of biologically important functions, highlighting potential ecological impacts of increased temperatures. Further, by considering available butterfly data on sex-biased gene expression in a comparative genomic framework, we find that the pattern of sex-biased gene expression identified in E. hecabe is highly species-specific, rather than conserved across butterfly species, suggesting that sex-biased gene expression responses to climate change are complex in butterflies. Conclusions Our study lays the foundation for further understanding of differential responses to environmental stress in a widespread lepidopteran model and demonstrates the potential complexity of sex-specific responses of lepidopterans to climate change.

Empathy is the ability to generate emotional responses (i.e., cognitive empathy) and to make cognitive inferences (i.e., affective empathy) to other people’s emotions. Empirical evidence suggests that patients with bipolar disorder (BD) exhibit impairment in cognitive empathy, but findings on affective empathy are inconsistent. Few studies have examined the neural mechanisms of cognitive and affective empathy in patients with BD. In this study, we examined the empathy-related resting-state functional connectivity (rsFC) in BD patients. Thirty-seven patients with BD and 42 healthy controls completed the self-report Questionnaires of Cognitive and Affective Empathy (QCAE), the Yoni behavioural task, and resting-sate fMRI brain scans. Group comparison of empathic ability was conducted. The interactions between group and empathic ability on seed-based whole brain rsFC were examined. BD patients scored lower on the Online Simulation subscale of the QCAE and showed positive correlations between cognitive empathy and the rsFC of the dorsal Medial Prefrontal Cortex (dmPFC) with the lingual gyrus. The correlations between cognitive empathy and the rsFC of the temporal–parietal junction (TPJ) with the fusiform gyrus, the cerebellum and the parahippocampus were weaker in BD patients than that in healthy controls. These findings highlight the underlying neural mechanisms of empathy impairments in BD patients.

Abstract Cerebellar dysfunction is associated with neurological soft signs (NSS), which is a promising endophenotype for schizophrenia spectrum disorders. However, the relationship between cerebellar-cerebral resting-state functional connectivity (rsFC) and NSS is largely unexplored. Moreover, both NSS and cerebellar-cerebral rsFC have been found to be correlated with negative symptoms of schizophrenia. Here, we investigated the correlations between NSS and cerebellar-cerebral rsFC, explored their relationship with negative symptoms in a main dataset, and validated the significant findings in a replication dataset. Both datasets comprised schizophrenia patients and healthy controls. In schizophrenia patients, we found positive correlations between NSS and rsFC of the cerebellum with the inferior frontal gyrus and the precuneus, and negative correlations between NSS and rsFC of the cerebellum with the inferior temporal gyrus. In healthy controls, NSS scores were positively correlated with rsFC of the cerebellum with the superior frontal gyrus and negatively correlated with rsFC between the cerebellum and the middle occipital gyrus. Cerebellar-prefrontal rsFC was also positively correlated with negative symptoms in schizophrenia patients. These findings were validated in the replication dataset. Our results suggest that the uncoupling of rsFC between the cerebellum and the cerebral cortex may underlie the expression of NSS in schizophrenia. NSS-related cerebellar-prefrontal rsFC may be a potential neural pathway for possible neural modulation to alleviate negative symptoms.

Abstract Negative symptoms, particularly the motivation and pleasure (MAP) deficits, are associated with impaired social functioning in patients with schizophrenia (SCZ). However, previous studies seldom examined the role of the MAP on social functioning while accounting for the complex interplay between other psychopathology. This network analysis study examined the network structure and interrelationship between negative symptoms (at the “symptom-dimension” and “symptom-item” levels), other psychopathology and social functioning in a sample of 269 patients with SCZ. The psychopathological symptoms were assessed using the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Positive and Negative Syndrome Scale (PANSS). Social functioning was evaluated using the Social and Occupational Functioning Assessment Scale (SOFAS). Centrality indices and relative importance of each node were estimated. The network structures between male and female participants were compared. Our resultant networks at both the “symptom-dimension” and the “symptom-item” levels suggested that the MAP factor/its individual items were closely related to social functioning in SCZ patients, after controlling for the complex interplay between other nodes. Relative importance analysis showed that MAP factor accounted for the largest proportion of variance of social functioning. This study is among the few which used network analysis and the CAINS to examine the interrelationship between negative symptoms and social functioning. Our findings supported the pivotal role of the MAP factor to determine SCZ patients’ social functioning, and as a potential intervention target for improving functional outcomes of SCZ.

Olfaction is an important medium of social communication in humans. However, it is not known whether olfactory function is associated with social network size. This study aimed to explore the underlying neural mechanism between olfactory function and social network. Thirty-one healthy individuals participated in this study. Social network size was estimated using the Social Network Index. Olfactory function was assessed with the Sniffin’ Stick Test. The results showed that there is a significant positive correlation between the size of an individual’s social network and their olfactory sensitivity. We also found that amygdala functional connectivity with the orbitofrontal cortex appeared to be related to olfactory sensitivity and social network size.