Search

Abstract Gasdermin-E (GSDME), the executioner of pyroptosis when cleaved by caspase 3, plays a crucial role in tumor defense and the response to chemotherapy drugs in cells. So far, there are poorly known mechanisms for the expression regulation of GSDME during cell death. Here, we identify the transcription factor Sp1 (Specificity protein 1) as a positive regulator of GSDME-mediated pyroptosis. Sp1 directly interacts with the GSDME promoter at −36 ~ −28 site and promotes GSDME gene transcription. Further, Sp1 knockdown or inhibition suppresses GSDME expression, thus reducing chemotherapy drugs (topotecan, etoposide, doxorubicin, sorafinib and cisplatin) induced cell pyroptosis. The regulation process synergizes with STAT3 (Signal transducer and activator of transcription 3) activity and antagonizes with DNA methylation but barely affects GSDMD-mediated pyroptosis or TNF-induced necroptosis. Our current finding reveals a new regulating mechanism of GSDME expression, which may be a viable target for the intervention of GSDME-dependent inflammatory diseases and cancer therapy.

Abstract Parkinson’s disease (PD), one of the most devastating neurodegenerative brain disorders, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) and deposits of α-synuclein aggregates. Currently, pharmacological interventions for PD remain inadequate. The cell necroptosis executor protein MLKL (Mixed-lineage kinase domain-like) is involved in various diseases, including inflammatory bowel disease and neurodegenerative diseases; however, its precise role in PD remains unclear. Here, we investigated the neuroprotective role of MLKL inhibition or ablation against primary neuronal cells and human iPSC-derived midbrain organoids induced by toxic α-Synuclein preformed fibrils (PFFs). Using a mouse model (Tg-Mlkl −/− ) generated by crossbreeding the SNCA A53T synuclein transgenic mice with MLKL knockout (KO)mice, we assessed the impact of MLKL deficiency on the progression of Parkinsonian traits. Our findings demonstrate that Tg-Mlkl −/− mice exhibited a significant improvement in motor symptoms and reduced phosphorylated α-synuclein expression compared to the classic A53T transgenic mice. Furthermore, MLKL deficiency alleviated tyrosine hydroxylase (TH)-positive neuron loss and attenuated neuroinflammation by inhibiting the activation of microglia and astrocytes. Single-cell RNA-seq (scRNA-seq) analysis of the SN of Tg-Mlkl −/− mice revealed a unique cell type-specific transcriptome profile, including downregulated prostaglandin D synthase (PTGDS) expression, indicating reduced microglial cells and dampened neuron death. Thus, MLKL represents a critical therapeutic target for reducing neuroinflammation and preventing motor deficits in PD.

Abstract Intention estimation has been widely studied in lane change scenarios, which explains a vehicle's behaviour and implies its future motion. However, in dense traffic, lane‐changing is more tactical and interactive. Due to the conflict between merging vehicles and adjacent vehicles, driving intentions become interdependent which fuses passing and yielding. In addition, lane change occurs without a fixed location. Drivers should be aware of each other's intentions along conflict process, and take instant responses. To address these challenges, this paper proposes semantic‐based interactive intention estimation (SIIE), to understand driving intentions during lane change conflict. The problem is addressed by combining driving semantics with probability inference model based on dynamic Bayesian network (DBN). Firstly, the DBN is modelled for the interaction process with Condition‐Intention‐Behaviour relationships. Secondly, the semantics are extracted from the lane change conflict and are inferred with observation methods. Thirdly, SIIE is trained and verified with real‐world driving data. The intention estimation results are demonstrated, and then utilized for multi‐modal motion identification and trajectory prediction. Lane change in dense traffic requires interactive cognition of driving intentions, the findings of this research shall inspire future studies into related scenarios, and promote interactive driving technologies.

This study investigated the beliefs, attitudes, and motivation of Thai and Chinese undergraduate students in relation to English language learning. Utilizing a mixed-method, explanatory sequential design, it aims to provide a better understanding of the three variables mentioned above. The quantitative data analysis showed disparities between the cohorts, with Chinese undergraduate students often displaying more robust orientations. However, the qualitative data analysis showed that both groups valued immersive learning experiences and technological integration. The research advocates for pedagogical frameworks in English education that align with overarching global paradigms while respecting individual cultural nuances. Such revelations are important for refining teaching practices and curricula to enhance genuine global literacy. It is also recommended that future research efforts diversify their cultural purview and give due consideration to variations in socio-economic contexts.

Previous studies have shown that the color red can affect basic motor functioning. However, these studies utilized simple gross motor tasks rather than those assessing complex fine motor skills. Moreover, these empirical studies were theoretically based on the threat–behavior link in human and non-human animals, and neglected the relationship between arousal and motor performance. According to the Yerkes–Dodson law and the inverted-U hypothesis in sport psychology, for simple motor tasks, high arousal (associated with the color red) is more advantageous than low arousal (associated with the color blue); for complex motor tasks, low arousal (blue color) is more advantageous than high arousal (red color). The current research examined the effect of color on different kinds of motor skills (fine motor and gross motor) based on the inverted U-hypothesis. In Experiment 1, we examined the effect of red and blue on dart-throwing performance, whereas in Experiment 2, we examined the effect of red and blue on grip strength performance. The results showed that performance of fine motor skill (dart-throwing) in the blue condition was better than in the red condition, and performance of gross motor skill (handgrip) in the red context was better than in the blue context. These results indicate that the type of motor skill assessed moderates the influence of red and blue on motor performance.

Previous studies have found a link between red and aggressive behavior. For example, athletes who wear red uniforms in sports are considered to have a competitive advantage. So far, most previous studies have adopted self-report methods, which have low face validity and were easily influenced by the social expectations. Therefore, the study used two implicit methods to further explore the association between red and aggressiveness. A modified Stroop task was used in Experiment 1 to probe college students’ differences between “congruent” tasks (i.e., red–aggressiveness and blue–agreeableness) and “incongruent” tasks (i.e., red–agreeableness and blue–aggressiveness). Result showed that participants responded more quickly to the congruent tasks than the incongruent tasks. Then, in order to adapt to the competitive context, Experiment 2 used an implicit association test with photos of athletes as the stimulus to college students and athletes to evaluate “congruent” tasks (i.e., red uniform photo-aggressiveness and blue uniform photo-agreeableness) as well as “incongruent” tasks (i.e., red uniform photo-agreeableness and blue uniform photo-aggressiveness), respectively. According to the results, both college students and athletes respond faster to congruent tasks than to incongruent tasks. Besides, athletes’ reactions to the red–aggressiveness association are faster than college students, which may relate to the athletes’ professional experience. The athletes may be more aggressive and impulsive. Overall, the study has attempted to examine the association between red and aggressiveness through implicit methods, but in the future, researches are need to find a deep association from brain mechanism aspect.

In order to well identify the 93 wild Cortex Daphnes samples from different species and habitats in western China and develop a standard operating procedure (SOP) for the authentication and quality of them in the future, a comprehensive and efficient identification system based on DNA barcoding and HPLC fingerprint technologies has been developed. The result showed that only 17 samples (18%) were Daphne giraldii Nitsche (DG), which is recorded in Chinese Pharmacopeia, while the others (82%) might have safety hazards. Additionally, the result of HPLC fingerprint analysis indicated that samples in the same species origins and wild distributions could be clustered together, which was consistent with DNA barcoding analysis. The study can provide a significant system for the authentication and quality of commercial Cortex Daphnes herbs. Undoubtedly, this study undoubtedly confirmed that the chemical compositions of Cortex Daphnes herbs were affected by both species origins and ecological environments, which is required more in-depth research.

This study investigated the beliefs, attitudes, and motivation of Thai and Chinese undergraduate students in relation to English language learning. Utilizing a mixed-method, explanatory sequential design, it aims to provide a better understanding of the three variables mentioned above. The quantitative data analysis showed disparities between the cohorts, with Chinese undergraduate students often displaying more robust orientations. However, the qualitative data analysis showed that both groups valued immersive learning experiences and technological integration. The research advocates for pedagogical frameworks in English education that align with overarching global paradigms while respecting individual cultural nuances. Such revelations are important for refining teaching practices and curricula to enhance genuine global literacy. It is also recommended that future research efforts diversify their cultural purview and give due consideration to variations in socio-economic contexts. [ABSTRACT FROM AUTHOR]